Manual For Reactor Produced Radioisotopes: IAEA-TECDOC-1340

IAEA-TECDOC-1340
Manual for
reactor produced radioisotopes
January 2003
The originating Section of this publication in the IAEA was:
Industrial Applications and Chemistry Section
International Atomic Energy Agency
Wagramer Strasse 5
P.O. Box 100
A-1400 Vienna, Austria
MANUAL FOR REACTOR PRODUCED RADIOISOTOPES

IAEA, VIENNA, 2003
IAEA-TECDOC-1340
ISBN 92–0–101103–2
ISSN 1011–4289
© IAEA, 2003
Printed by the IAEA in Austria
January 2003
FOREWORD
Radioisotopes find extensive applications in several fields including medicine, industry,

agriculture and research. Radioisotope production to service different sectors of economic
significance constitutes an important ongoing activity of many national nuclear programmes.
Radioisotopes, formed by nuclear reactions on targets in a reactor or cyclotron, require further
processing in almost all cases to obtain them in a form suitable for use. Specifications for final
products and testing procedures for ensuring quality are also an essential part of a radioisotope
production programme.
The International Atomic Energy Agency (IAEA) has compiled and published such
information before for the benefit of laboratories of Member States. The first compilation,
entitled Manual of Radioisotope Production, was published in 1966 (Technical Reports Series
No. 63). A more elaborate and comprehensive compilation, entitled Radioisotope Production
and Quality Control, was published in 1971 (Technical Reports Series No. 128). Both served
as useful reference sources for scientists working in radioisotope production worldwide. The
1971 publication has been out of print for quite some time.
The IAEA convened a consultants meeting to consider the need for compiling an
updated manual. The consultants recommended the publication of an updated manual taking
the following into consideration:
– significant changes have taken place since 1971 in many aspects of radioisotope
production;
– many radioisotopes have been newly introduced while many others have become
gradually obsolete;
– considerable experience and knowledge have been gained in production of important
radioisotopes over the years, which can be preserved through compilation of the manual;
– there is still a need for a comprehensive manual on radioisotope production methods for
new entrants to the field, and as a reference.
It was also felt that updating all the subjects covered in the 1971 manual at a time may
not be practical considering the numerous new developments that have taken place since then.
Hence in this manual it was decided to focus only on reactor produced radioisotopes. This
manual contains procedures for 48 important reactor-produced isotopes. These were
contributed by major radioisotope producers from different parts of the world and are based
on their practical experience. In case of widely used radioisotopes such as 131I, 32P and 99Mo,
information from more than one centre is included so that the users can compare the
procedures.
As in the earlier two versions, a general introductory write-up is included covering basic
information on related aspects such as target irradiation, handling facilities, radiation
protection and transportation, but in less detail. Relevant IAEA publications on such matters,
particularly related to radiation protection and transportation, should be referred to for
guidelines. Similarly, the nuclear data contained in the manual are only indicative and the
relevant databases should be referred to for more authentic values.
It is hoped that the manual will be a useful source of information for those working in
radioisotope production laboratories as well as those intending to initiate such activities.
The IAEA wishes to thank the consultants and all the contributors for their co-operation
in compiling the manual. The IAEA officers responsible for this publication were
D.V.S. Narasimhan and H. Vera Ruiz of the Division of Physical and Chemical Sciences.
EDITORIAL NOTE
This publication has been prepared from the original material as submitted by the authors. The views
expressed do not necessarily reflect those of the IAEA, the governments of the nominating Member
States or the nominating organizations.
The use of particular designations of countries or territories does not imply any judgement by the
publisher, the IAEA, as to the legal status of such countries or territories, of their authorities and
institutions or of the delimitation of their boundaries.
The mention of names of specific companies or products (whether or not indicated as registered) does
not imply any intention to infringe proprietary rights, nor should it be construed as an endorsement
or recommendation on the part of the IAEA.
The authors are responsible for having obtained the necessary permission for the IAEA to reproduce,
translate or use material from sources already protected by copyrights.
CONTENTS
1. PRINCIPLES OF PRODUCTION, PROCESSING AND HANDLING

OF RADIOISOTOPES ........................................................................................................ 1
1.1. Introduction ................................................................................................................ 1
1.2. Research reactors for isotope production ................................................................... 2
1.3. Nuclear reactions........................................................................................................ 2
1.3.1. Energy of neutrons in pile .............................................................................. 4
1.3.2. Cross-section.................................................................................................. 4
1.3.3. Types of nuclear reactions ............................................................................. 4
1.4. Calculation of radioisotope yield ............................................................................... 6
1.4.1. Corrections to the activation equation ........................................................... 7
1.4.2. Self-shielding effect ...................................................................................... 7
1.4.3. Power variation in the reactors....................................................................... 8
1.4.4. Corrections for burnup of the target and destruction of target atoms ............ 8
1.4.5. Irradiation efficiency...................................................................................... 9
1.5. Irradiation techniques ............................................................................................... 10
1.5.1. Choice of target material ................................................................................ 10
1.5.2. Target encapsulation ...................................................................................... 11
1.5.3. Safety evaluation of in-pile irradiation and experimental assemblies............ 11
1.6. Laboratory facilities for radioisotope production..................................................... 11
1.6.1. Layout and basic infrastructure .................................................................... 12
1.6.2. Radiological protection ................................................................................ 13
1.6.3. Radioisotope handling facilities................................................................... 13
1.6.4. Ventilation.................................................................................................... 16
1.6.5. Management of radioactive waste................................................................ 16
1.6.6. Surveillance and monitoring ........................................................................ 17
1.7. Packing and transportation of radioisotopes ........................................................... 18
1.7.1. Transport regulations ................................................................................... 18
1.7.2. Types of packages ........................................................................................ 18
1.7.3. Categories of packages................................................................................. 20
1.8. Conclusion................................................................................................................ 20
Bibliography to Section 1......................................................................................................... 21
2. PRODUCTION AND PROCESSING METHODS FOR

INDIVIDUAL RADIOISOTOPES
Bromine-82 (82Br35).................................................................................................................. 25
Calcium-45 (45Ca20) ................................................................................................................. 29
Carbon-14 (14C6) ...................................................................................................................... 31
Chromium-51 (51Cr24) .............................................................................................................. 35
Cobalt-58 (58Co27) .................................................................................................................... 41
Cobalt-60 (60Co27) .................................................................................................................... 44
Copper-64/Copper-67 (64Cu29, 67Cu29)..................................................................................... 51
Dysprosium-165 (165Dy66)........................................................................................................ 58
Dysprosium-166 (166Dy66)...................................................................................................... ..60
Gadolinium-153 (153Gd64) ....................................................................................................... .62
Gold-198 (198Au79) .................................................................................................................. .63
Gold-199 (199Au79) ................................................................................................................... 66
Gold-199 (199Au79) (Alternate procedure)................................................................................ 69
Holmium-166 (166Ho67)............................................................................................................ 71
Iodine-125 (125I53)..................................................................................................................... 75
Iodine-131 (131I53) (Wet distillation method) ........................................................................... 82
Iodine-131 (131I53) (Dry distillation method)............................................................................ 86
Iodine-131 (131I53) (Dry distillation method (Alternate procedure).......................................... 90
Iodine-131(131I53) (Dry distillation method (Alternate procedure)........................................... 95
Iodine-131 (131I53) (Dry distillation method (Alternate procedure)........................................ 102
Iodine-131 (131I53) (Fission product) ...................................................................................... 111
Iridium-192 (192Ir77)................................................................................................................ 116
Iron-59 (59Fe26) ....................................................................................................................... 118
Lutetium-177 (177Lu71) ........................................................................................................... 121
Lutetium-177 (177Lu71) (Alternate procedure)........................................................................ 124
Mercury-197 (197Hg80)............................................................................................................ 129
Mercury-203 (203Hg80)............................................................................................................ 132
Molybdenum-99 (99Mo42) (Fission product) .......................................................................... 135
Molybdenum-99 (99Mo42) (By neutron irradiation) ............................................................... 141
Nickel-63 (63Ni28)................................................................................................................... 143
Osmium-191 (191Os76)............................................................................................................ 145
Osmium-194 (194Os76)............................................................................................................ 150
Palladium-103 (103Pd46).......................................................................................................... 154
Palladium-109 (109Pd46).......................................................................................................... 156
Phosphorous-32 (32P15)........................................................................................................... 158
Phosphorus-32 (32P15) (Alternate procedure) ......................................................................... 161
Phosphorus-33 (33P15)............................................................................................................. 167
Platinum-195m (195mPt78) ....................................................................................................... 171
Rhenium-186 (186Re75) ........................................................................................................... 179
Rhenium-186 (186Re75) (Alternate procedure)........................................................................ 183
Rhenium-188 (188Re75) ........................................................................................................... 186
Samarium-153 (153Sm62) ........................................................................................................ 189
Scandium-46 (46Sc21) ............................................................................................................. 193
Scandium-47 (47Sc21) ............................................................................................................. 194
Silver-111 (111Ag47)................................................................................................................ 198
Sodium-24 (24Na11) ................................................................................................................ 203
Strontium-89 (89Sr38).............................................................................................................. 206
Strontium-89 (89Sr38) (Alternate procedure) .......................................................................... 212
Sulphur-35 (35S16)................................................................................................................... 217
Tellurium-123m (123mTe52)..................................................................................................... 220
Thallium-204 (204Tl81)............................................................................................................ 222
Thulium-170 (170Tm69)........................................................................................................... 224
Tin-113 (113Sn50) .................................................................................................................... 226
Tin-117m (117mSn50) ............................................................................................................... 230
Tungsten-188 (188W74) ........................................................................................................... 233
Ytterbium-169 (169Yb70)......................................................................................................... 238
Yttrium-90 (90Y39).................................................................................................................. 244
Xenon-133 (133Xe54) .............................................................................................................. 248
CONTRIBUTORS TO DRAFTING AND REVIEW............................................................ 253
1. PRINCIPLES OF PRODUCTION, PROCESSING AND
HANDLING OF RADIOISOTOPES
1.1. Introduction
Radioisotopes find wide-ranging applications in various fields, including industry,

research, agriculture and medicine. Production of radioisotopes, radiolabel led compounds,
radiation sources and other products based on radioisotopes constitute important activities of
several national nuclear programmes. These often support several areas of national economic
significance such as health care services and industrial quality control. Two major sources of
artificial radioisotopes are accelerators and reactors. Radioisotopes produced in reactors
represent a large percentage of the total use of radioisotopes due to a number of factors. The
reactor offers large volume for irradiation, simultaneous irradiation of several samples,
economy of production and possibility to produce a wide variety of radioisotopes. The
accelerator-produced isotopes relatively constitute a smaller percentage of total use. The
accelerators are generally used to produce those isotopes which can not be produced by
reactor or which have unique properties.
The isotope production programme involves several interrelated activities such as target
fabrication, irradiation in reactor or accelerator, transportation of irradiated target to
radioactive laboratory, radiochemical processing or encapsulation in sealed source, quality
control and transportation to end users. Each step needs experts from respective disciplines,
laboratory facilities equipped for radioactivity handling and other supporting infrastructure.
Radioisotope production started on a significant scale in several countries with the
commissioning of research reactors starting from the late 1950s. In 1966 the IAEA published
a compilation of procedures for production of 15 radioisotopes. It also contained an
introductory chapter covering the handling and processing facilities, radiation protection
aspects and applications among others. The years 1955 to 1970 witnessed rapid growth in
construction of new research reactors and corresponding increase in radioisotope production
and utilization. In response to this the IAEA published an updated manual in 1971 which
covered 25 reactor-produced isotopes and 8 accelerator produced isotopes. In addition it also
included preparation of radioisotope generators and radiolabel led compounds. As in the
earlier volume, this also contained an introductory chapter covering related aspects such as
irradiation techniques and handling. Both publications served as useful references for
laboratories engaged in and initiating radioisotope production and supply programmes the
world over. The 1971 publication has been out of print for quite sometime. Publication of an
updated manual was considered in a consultants meeting organized in 1998. The meeting
considered publications on the topic available from other sources, need for a reference
manual, developments in isotope production that have taken place since 1971, changes in the
pattern of use and the need to preserve the expertise developed over the years in several
centres. It recommended that the IAEA should bring out an updated manual. The meeting also
made recommendations on the proposed contents of the manual. The earlier publications
contained detailed procedures followed in different centres for the same isotope. For example,
for 131I production, the first and second contained 13 and 17 procedures, respectively. It was
recommended that typical procedures followed from representative laboratories be compiled.
Based on the information available from responses to a questionnaire from the IAEA to
different isotope producers and on the consultants’ personal information, they also suggested
the contributors for each isotope. Unlike the 1971 publication, the meeting felt that the
compilation of information be done in stages, the first one to be focused on reactor-produced
isotopes. A format in which the contributions are to be sought was also suggested. The
1
identified laboratories were requested to submit their contributions in this format. By and
large all contributors followed the given format. But still some variations in the presentation
of technical information and additional data were observed and nevertheless accepted. The
contributions received are included with minimum editing. The consultants were also in
favour of including a brief introductory write-up covering the essentials of related aspects,
such as irradiation and handling techniques. The availability of several IAEA publications
related to transportation of radioisotopes, radiological safety and radioactive waste handling
was given consideration and these aspects are only briefly referred to.
1.2. Research reactors for isotope production
The first operating nuclear reactor that used natural uranium as fuel and graphite blocks
as moderator (graphite reactor) was constructed in Oak Ridge, Tennessee, USA and operated
from 1943 to 1963.
The IAEA maintains a worldwide directory of research reactors. The period from 1950
to 1970 saw construction of a large number of research reactors with multiple facilities. After
1980, because of the decommissioning of many old ones, the number of operating reactors has
been steadily decreasing. At present there are 278 research reactors in operation of which
nearly 73 are useful for regular isotope production.
The research reactors used for radioisotope production could be broadly classified into:
– enriched uranium, light water moderated, swimming pool type reactors (FIG. 1-1)
– natural uranium, heavy water moderated and cooled tank type reactors (FIG. 1–2).
Radioisotopes are produced by exposing suitable target materials to the neutron flux in a
nuclear reactor for an appropriate time. In swimming pool type reactors, the core is compact
and visible, and is accessible from the top of the pool. Target materials to be irradiated are
sealed in primary capsules, loaded in specially designed irradiation jigs and then lowered in
predetermined locations in the core for irradiation. In swimming pool reactors, the core being
easily accessible, loading and unloading of targets are easy, and can be carried out from top of
the pool using simple devices. The irradiated targets are then loaded in appropriate shielding
containers and transported to the radioisotope processing laboratories.
In the tank type reactors, the irradiation assemblies contain a large number of target
capsules and are lowered using specially designed jigs. The irradiation assembly is lowered
into a hot cell fitted with master slave manipulators for carrying out loading and unloading of
target capsules subsequent to irradiation.
Production of quality radioisotopes with high specific activity will depend on the target
as well as irradiation conditions.
1.3. Nuclear reactions
Factors that determine the type of nuclear reaction taking place and the rate of
production of the product are:
– energy of the neutrons and the neutron flux
– characteristics of the target material
– activation cross-section for the desired reaction.
2
FIG. 1-1. Cerenkov radiation in the core of swimming pool reactor.
FIG. 1-2. The reactor block of a tank type reactor with irradiation facilities.
3
1.3.1. Energy of neutrons in pile
The pile neutrons are classified according to their energy as follows:
1.3.1.1. Thermal neutrons
Thermal neutrons are those which are in thermal equilibrium with molecules/atoms of
the surrounding medium. The energy distribution of this group of neutrons can be represented
by Maxwellian distribution. The thermal neutrons have energy of about 0.025 eV at a
temperature of 20°C.
1.3.1.2. Epithermal neutrons
These are neutrons of intermediate energy, normally in the keV region. The 1/E law can
represent their distribution.
1.3.1.3. Fast neutrons
Fast neutrons are neutrons with high energy (above 1 MeV). They have an energy
distribution similar to that of fission neutrons.
The distribution of neutrons in the three groups is different at different locations in the
reactor. For example in the reactor core, the fast neutron percentage will be higher, whereas as
one approaches the periphery of the reactor, the fast neutrons flux will decrease.
1.3.2. Cross-section
The neutron interaction with the nucleus of the target material can be expressed
quantitatively in terms of the nuclear cross-section, which is a measure of the probability that
the given reaction takes place. This can be expressed in terms of an imaginary cross sectional
area presented by the nucleus around the nucleus to the beam of neutrons, perpendicular to the
beam, such that if and only if the neutrons pass through this area, the nuclear reaction takes
place. The unit of cross-section is barn (one barn = 10-24 cm2). The value of cross-section
varies with energy of the neutrons and from nucleus to nucleus.
In general, slower the neutron, greater is the probability for the reaction. Hence thermal
neutrons have the maximum value for the cross-section. In this region, cross-section varies as
‘1/v’, where v is velocity of neutrons. Normally the cross-section values are quoted at room
temperature (20°C).
If the moderator temperature is high, the cross-section value will have to be corrected
for the temperature.
As the energy of neutrons increases to epithermal region, the cross-section shows sharp
variation with energy, with discrete sharp peaks or resonances.
At very high neutron energies, the cross-section value decreases sharply.
1.3.3. Types of nuclear reactions
Some of the major nuclear reactions that are used for radioisotope production are given
below:
4
1.3.3.1. (n,J) reaction
Most of the reactor-produced radioisotopes, are products of the (n,J) reaction. This
reaction is also referred to as radiative capture and is primarily a thermal neutron reaction.
Some of the common radioisotopes produced by (n,J) reactions are:
1
59
27 Co + 0 n o 27
60
Co + J (V = 36 barn)
191
77 Ir + 0 n1 o 192
77 Ir + J (V = 370 barn)
98
42 Mo + 0 n1 o 99
42 Mo + J (V = 0.11 barn)
Here, the product is an isotope of the target element itself and hence cannot be
chemically separated. Therefore the specific activity is limited by the neutron flux available in
the reactor.
1.3.3.2. (n, J) oE reaction
In some cases the (n,J) reaction produces a very short-lived radioisotope, which decays
by beta emission to a different radioisotope.
Example:
130
52 Te+ 0 n1 o 131
52Te * + J (V = 67 millibarn)
131
52 Te* o E + 131
53 I
The product can be chemically separated from the target. This will enable us to obtain
high specific activity or carrier free radioisotope.
1.3.3.3. (n, p) reaction
In some cases the absorption of neutron leads to emission of a proton as outgoing

particle. Such a reaction is termed as (n, p) reaction, caused by fast neutrons having energy
more than a particular value known as threshold energy. Hence, such a reaction is known as
threshold reaction.
Examples:
58
28 Ni + 0 n1 o 27
58
Co+ 1 p1 (V = 4.8 barn)
32
16 S+ 0 n1 o 32
15 P + 1 p
1
(V = 165 millibarn)
Also in this case, the product nucleus can often be chemically separated from the target,
thereby obtaining very high specific activity product.
1.3.3.4. (n,D) reaction
This reaction is also a threshold reaction as neutrons having energy above a specific
value (threshold energy) is absorbed by the nucleus causing an alpha particle to be ejected. In
some very special cases, the reaction is caused by thermal neutrons as well.
5
Example:
6
3 Li + 0 n1 o 1 H 3 + 2 He 4 (V = 980 barns)
High specific activity/carrier free products could also be obtained in this.
1.3.3.5. Multistage reactions
There are certain radioisotopes that are produced by multistage processes or successive
neutron capture:
Example:
186
W (n,J) 187W (n,J) 188W
1.3.3.6. Fission
Thermal neutron induced fission of uranium-235 provides a host of useful radioisotopes.

Each fission provides two fission fragments. The fission products fall into two definite
groups, one light group with a mass number of around 95 and a heavy group with a mass
number of around 140. The fission yield of a nuclide is a fraction or the percentage of the total
number of fissions, which leads directly or indirectly to that nuclide. The total fission yield is
200%. In addition, some fission products undergo successive decays, leading to production of
decay products forming a fission decay chain. Some of the most important fission products
that find useful applications are:
99 131
Short lived fission products o 42 Mo, 53 I
137 147 90
Long lived fission products o 55 Cs, 61 Pm, 38 Sr
1.4. Calculation of radioisotope yield
When a target is under irradiation in a reactor, the activation per second can be
represented by:
dN'
= nv V act N T (1)
dt
where
NT is the total number of atoms present in target,
nv is neutron flux = I,
Vact is activation cross-section,
N’ the number of activated atoms,
A atomic weight of the target.
Equation 1 considers the neutron flux to be isotropic. In case the neutrons are not
mono-energetic and if a velocity distribution exists, then the average value of the flux is to be
considered.
Since the product radioisotope starts decaying with its own half-life, once production
starts Equation 1 representing net growth rate of active atoms can be written as:
6
dN'
= I V act N T O N ' (2)
dt
where
ON’ indicates the decay rate of product nucleus.
Equation 2 can be solved to determine the value of radioactive atoms at time ‘t’, as
follows:
0.6V I
S= (1 e Ot ) %q / g (3)
A
where
V is the neutron activation cross-section leading to the production of radioisotope of

interest in barn,
I is the flux in n/cm2/s,
t is the time of irradiation,
O is the decay constant = 0.693/T½.
A is atomic weight of target element
When t » T½, we get saturation activity
0.6V I
S= Bq / g
A (4)
Equation 3 clearly shows that growth of activity in a target under irradiation is

exponential in nature and reaches a saturation value limited by the neutron flux in the reactor.
1.4.1. Corrections to the activation equation
In practice, the activity induced in the target under irradiation will be less than the
activity calculated using the above equation, due to several factors, such as:
– self shielding effect in the target

– power variation in the reactor
– flux depression due to adjacent samples in the reactor especially when such samples are
high neutron absorbers
– burn up of the target material with time
– destruction of the product nucleus due to subsequent neutron capture.
1.4.2. Self-shielding effect

This becomes predominant in case of targets with high activation cross-section where
the neutron flux in the volume of the target gets reduced, thereby decreasing the activity build
up. The correction factor f depends upon the geometry of target and can be evaluated
theoretically using the equation given below:
7
The neutron self-shielding factor is:
1
f= (1 e 2 L ) (5)
2L
Volume
W = 2¦ a'
Surface area
in which
where
6a´ is the microscopic absorption cross-section.
FIG. 1-3 shows the self-shielding factor for the slab and sphere of various thicknesses. It
is rather difficult to arrive at a suitable correction factor for odd geometry. It is preferable to
establish such factors by actual trial irradiation in the reactor.
FIG. 1-3. Self-shielding factor for slab and sphere.
1.4.3. Power variation in the reactors
It is difficult to theoretically evaluate the effect of power variation on the activity

buildup in the target except by following the operating history of the reactor and applying
decay corrections as applicable.
1.4.4. Corrections for burnup of the target and destruction of target atoms
The above effects become predominant in the long term irradiation of targets with high
activation cross-sections, such as production of cobalt-60.
8
In such cases the net rate of growth of the product nucleus could be written as:
dN'
= N a act I O N ' N ' V 'ab I (6)
dt
where
N is equal to N 0 e V ab I t ,
Vact is the activation cross-section for product nucleus,
O is the decay constant of product nucleus,
N’ is the number of product atoms at time t,
I is the neutron flux,
Vab is absorption cross-section of the target causing target burn up,
V’ab is absorption cross-section of the product nucleus.
Equation 6 can be solved to obtain specific activity S, as follows:
0.6 V act I O KT Ct
S= (e e ) Bq / g (7)
A (C K)
where
S is specific activity,
K is equal to Vab I,
C is equal to O+V ab’ I.
A is atomic weight of target.
From Equation 7, irradiation time for obtaining maximum specific activity tm is found as
log(C / K)
tm= (C K) (8)
For example, in the case of cobalt-60 production by irradiation of cobalt metal pellets, it
could be seen that at a flux of 4×1013 n/cm2/s, maximum attainable specific activity is
225 Ci/g in approximately 11 years (FIG. 1-4). Whereas at a flux of, approximately
1014 n/cm2/s, the specific activity reaches a maximum value at the end of seven years of
irradiation to 370 Ci/g and, thereafter, decreases with time. At a flux of 2×1014 n/cm2/s, a
maximum activity of 325 Ci/g can be reached after an irradiation for three and a half years.
Irradiation beyond the time indicated above will tend to reduce the specific activity.
1.4.5. Irradiation efficiency
The ratio of the activity actually produced in the target to the activity calculated using
the basic growth equation is referred to as the irradiation efficiency. It depends on the
cumulative effects of all factors referred to above. This factor should be experimentally
determined by trial irradiation. This factor could vary from 90% to as low as a value as 10%.
9
FIG. 1-4. Production of cobalt-60 in various neutron fluxes with cobalt metal target.
1.5. Irradiation techniques
1.5.1. Choice of target material
The following points should be kept in mind while selecting a target material for
irradiation in a reactor.
– Substances which are explosive, pyrophoric, or volatile, are not to be irradiated in the
reactor.
– As a policy, in many reactors, mercury in elemental form is not permitted to be
irradiated since most of reactor components are made of aluminium and an amalgam
could be formed when aluminium comes into contact with mercury.
– Targets should be stable under irradiation conditions. It should not decompose under
irradiation to form any gaseous products. Generally unstable products like
hydrocarbons, are not permitted to be irradiated except under extremely controlled
conditions.
– High purity targets should be irradiated to avoid production of unwanted radionuclides.
– Enriched target materials will enable production of radioisotopes with higher specific
activity.
– Physical form of the target or the target geometry should be such that self absorption is
minimum.
– Target should be in a suitable chemical form to enable easy post irradiation processing.
Usually targets in metallic forms or oxides are preferred.
– Whenever long lived radioisotopes like cobalt-60, iridium-192 are involved, the size and
shape of the targets and encapsulation should be so chosen that the irradiated assembly
could preferably be used as such for the intended purpose.
10
– If the target is hygroscopic in nature, it is preferable to pre-heat and completely dry the
target prior to encapsulation.
– Since targets in metallic form like cobalt do contain certain amount of adsorbed gases
like hydrogen, nitrogen, etc. such targets should be de-gassed in an inert atmosphere
before encapsulation. Targets like cobalt are normally plated with nickel, to avoid oxide
formation leading to contamination during post irradiation handling.
1.5.2. Target encapsulation
Target materials should be properly encapsulated in suitable containers before

introducing in the reactor. Choice of the encapsulation material and method of encapsulation
will depend upon various factors, such as:
– physical form of target (solid, liquid or gas)

– characteristics of target
– duration of irradiation
– design of the irradiation assembly in the reactor
– type of coolant used in the reactor
– post irradiation handling proposed
– end-use of radioisotope.
The most commonly used encapsulation materials are aluminium, zircaloy and stainless
steel. However, majority of targets is encapsulated in aluminium capsules. Aluminium is
chosen as the material for fabrication of irradiation capsules because of the following reasons:
– Absorption cross-section is low (aluminium is considered as nearly transparent to

neutrons).
– Radioisotopes produced in the aluminium capsule material are very short lived, hence
post irradiation handling and disposal are easy.
– Good thermal conductivity, hence heat produced in the target is easily transferred to the
coolant.
– It is possible to make air/water tight container by cold welding a lid to the container
with the target material inside. This has the advantage of not subjecting the targets to
high temperature thus avoiding oxidation/decomposition of the target.
Cold welded capsules are generally tested for leak tightness before irradiation, either by
hot water bath bubbling test, or by using ethylene glycol. A helium leak test is also possible to
conduct if helium is admitted in the capsule while sealing.
1.5.3. Safety evaluation of in-pile irradiation and experimental assemblies
It is required to thoroughly evaluate a target material or an assembly to be introduced in

a reactor to ensure their safety and that of the reactor. Evaluation should mainly consist of
calculation of reactivity effects, calculation of nuclear heating effects, radioactivity produced
in the target and radiation shielding for safe handling and transport of the irradiated materials.
1.6. Laboratory facilities for radioisotope production
During irradiation of target a number of radionuclides of different half-lives and

energies can be produced along with the radioisotope of interest. The irradiated target will
often require chemical processing to separate the radioisotope of interest. The radioisotope
11
may also often have to be further processed and purified to obtain a product which could be
used effectively and safely for the intended purpose.
It will be ideal to locate such a radioisotope processing facility in the vicinity of a

research reactor, preferably with facilities for direct transfer of irradiated targets into
processing plants. A typical radioisotope production facility could consist of the following
specialized facilities and capabilities:
– facilities for processing low level radioisotopes involving simple procedures like
dilution, dispensing, etc.
– facilities for processing medium level radioisotopes involving complex procedures like
purification
– facilities for processing high level radioisotopes, e.g. cobalt-60, fission products,
molybdenum-99, etc. which will need heavily shielded hot cells and allied facilities
– quality control laboratories
– health physics monitoring set-up
– analytical laboratories
– research and development laboratories
– counting room consisting of E, J counting instruments, multichannel analyser, etc.
– animal house, in case the programme involves production of radiopharmaceuticals
– decontamination room for personnel and equipment
– radioactive solid waste storage room with lead shielded cell
– radioactive consignment packing room
– stores
– workshop
– offices.
The extent of the facilities to be included and areas to be allocated will depend on the
volume of activities.
1.6.1. Layout and basic infrastructure
Since a radioisotope production facility will be handling radioisotopes with different

levels of activities, suitable airlock or double door systems should ideally separate the
facilities. These areas will need different ventilation supplies.
The laboratory areas can be broadly categorized as high active and low active areas,
depending upon the levels of activities handled. While designing a laboratory, it would be
appropriate to locate the high active area in the central portion of the facility, whereas
peripheral rooms or areas could be used for low levels laboratories, inactive laboratories as
well as offices. Entry into the high active areas should be through barriers. This arrangement
will enable segregation of the low active and high active areas, keeping intact their functional
relationship.
Utility services at the laboratory can include:
– hot and cold water

– compressed air
– vacuum lines
– electrical connections
– specific gas supplies, as required.
12
In addition, appropriate waste collection and disposal system needs to be incorporated.
There is also a need to provide a low level effluent collection tank with sufficient capacity
(say, for effluents generated over a week).
The flooring of such radiochemical laboratories is preferably covered with replaceable

plastic tiles and the walls painted such that it can be easily washed and decontaminated.
1.6.2. Radiological protection
The design of a radioisotope production facility should take into account appropriate
radiation protection rules, which aim to limit radiation exposures of occupational workers to
acceptable limits, both from the point of view of acute radiation effects and delayed effects of
radiation. Adopting safety standards set on the basis of relevant IAEA publications can attain
these objectives. Safety measures in any installation are to be included in the planning stage
by giving adequate consideration for control of external radiation and contamination hazards.
Planning should also provide for appropriate emergency preparedness. The nature of
radioactivity as well as the processing and handling operations involved is to be considered
while providing for external radiation control. Adequate shielding should be provided to keep
the radiation levels to acceptable levels.
In a permanent facility, acceptable levels of radiation are achieved by providing fixed

shielding (iron, lead or concrete) around handling facilities. The exact shield design depends
on nature and energy of radiation. Remote handling devices such as tongs, master slave
manipulators, etc. can be used for performing various operations through the shield.
Contamination can occur and easily spread in working environment unless adequate
steps for confinement of radioactivity are taken at all stages of operations. The presence of
radioactive materials on the surfaces in concentration greater than derived working levels
(DWL) may result in significant uptake by ingestion and inhalation routes. The training of
workers in radiological safety and implementation of proper operating procedures plays an
important role in the maintenance of radiologically safe conditions.
Inhalation is a possible way of intake by workers of airborne radioactive materials.

Providing containment commensurate with the degree of hazard associated with operations
minimizes inhalation hazard. However, some air contamination may arise due to breach of
containment. A well-designed ventilation system should pick up this contamination and
prevent its spread to other working areas under normal operating conditions. Negative
pressure and suitable air changes should be maintained in the laboratory.
The incidents or accidents that could occur in radioisotope laboratories range from small
radioactive spillage which can be controlled quickly without much radiological significance to
a severe accidents involving large amounts of radioactive materials which could result in high
external and internal exposure. Fire incidents involving large quantity of radioactive material
are equally serious. Adequate emergency plans should be in place to tackle such occurrences.
1.6.3. Radioisotope handling facilities
Radioisotope processing laboratories are provided with handling facilities, such as fume
hoods, glove boxes, shielded tong boxes, and hot cells.
13
(1) Fume hoods
Fume hoods are generally used when contamination and external hazards are not significant. It
is a partial enclosure and the opening of the panel provides an access to the material being
handled (FIG. 1-5). The face velocity of air (0.5–0.75 m/s) at the fume hood opening should
be comparable to or greater than capture velocity for the particular contaminant likely to be
released into fume hood atmosphere. Utility services such as lighting, electrical power,
instrument air and water are provided inside the fume hood. The quantities of radioactivity
handled in fumehood are limited by their toxicity grading.
FIG. 1-5. Fume hood for handling radioisotopes.
(2) Glove boxes
When quantity of radioactive material being handled exceeds the limit prescribed for a fume
hood, the operation should be carried out in a glove box. A glove box is a total containment
system, which completely isolates the hazardous materials from the operator’s environment
(FIG. 1-6). It is made up of mild steel, stainless steel or aluminium coated with epoxy paints.
They are provided with laminated safety glass panels for viewing. The gloves are made of
neoprene with thickness varying from 0.2 mm to 1.4 mm.
The degree of leak tightness may vary from a few percentage of box volume per hour for
simple chemical operations to less than 0.05% box volume per hour for dry and dusty
operations.
14
FIG. 1-6. A view of typical glove box.
(3) Shielded tong boxes
Lead shielded tong boxes are very often used in radioisotope laboratory (FIG. 1-7). The
lead shield thickness varies from 50 mm to 200 mm.
They are fabricated out of mild steel frame and aluminium panels with perspex viewing
windows. Up to several curies of gamma emitting isotopes are routinely handled in such
facilities. They are fitted with tongs or mini manipulators for handling. Lead glass viewing
windows with glass thickness equivalent to lead shield are also provided.
FIG. 1-7. Shielded tong boxes for processing of radioisotopes.
15
(4) Hot cells
A hot cell is a large volume shielded enclosure in which operations are carried with
master slave manipulators, FIG. 1-8. The cell walls are usually made of concrete. These are
used for handling kilocurie quantities of gamma emitters.
FIG. 1-8. Hot cells with master slave manipulators.
1.6.4. Ventilation
Ventilation is the most important and expensive part of the radioactive laboratory where large
quantity of radioactive materials are handled (class A laboratory). The general laboratory
ventilation system consists of a balanced supply and exhaust of air. The air supply in isotope
production laboratory is a once-through system. The air is conditioned for human comfort and
for stable operation of electronic equipment and counting systems. The airflow always follows
the pattern from inactive to low active to high active areas to prevent spread of air borne
contamination. The major part of the laboratory air is exhausted through a bank of HEPA
filters and is released through a stack.
The glove box and other handling facilities have no separate air supply but draw air
from the surroundings through leakage and, in certain cases, through designed air inlet points.
1.6.5. Management of radioactive waste
During the operation of a radioisotope laboratory several types of non-radioactive and

radioactive wastes are generated. The radioactive waste should be segregated and managed
16
following guidelines given in relevant IAEA publications. They consist of solid, liquid and
gaseous wastes.
(1) Solid wastes
Radioactive solid waste consists of tissue papers/absorbent sheets, glass wares,

protective wears such as hand gloves, shoe covers, worn out metallic parts, equipment, mops
and spent radiation sources. They should be categorized by their level of radioactivity, heat
content, potential hazards and/or method of treatment. For general purposes, wastes are
labelled as low level, medium level, high level and alpha bearing wastes. Radioactive solid
wastes with relatively high radioactivity content should be collected in appropriate shielded
containers. Low level wastes should be segregated as combustible, non-combustible and
compressible wastes. These are then sent to the waste management facility for further
treatment/disposal.
(2) Liquid wastes
Low and medium active liquid wastes from laboratories should be collected first in a
hold up tank and pumped/transported to the treatment facility after checking for activity
content. High active liquid wastes generated during processing of radioisotopes should be
stored for sufficient period to allow activity to decay before transporting to the treatment
plant.
(3) Gaseous wastes
These wastes are mainly in the form of ventilation air and, in few cases, consist of
volatile products generated during processing of radioisotopes such as fission products and
I131.
Management of gaseous wastes should be an integral part of the plant ventilation

system. Exhaust air should be filtered through HEPA filters. Activated charcoal filters should
also be used as primary filters for effective removal of volatile isotopes such as I131. Gaseous
wastes should then be discharged through a tall stack.
1.6.6. Surveillance and monitoring
The radioisotope laboratory should have a system of radiological surveillance and

monitoring following guidelines in IAEA publications. The main objectives of monitoring
system are to prevent deterioration of radiological conditions in the plant and to avoid
unnecessary exposure of personnel.
(1) Personnel monitoring
It includes monitoring of external exposure by personnel monitoring devices such as

film badges or thermoluminescent dosimeters (TLD), and of internal contamination by
bioassay (either urine or fecal sampling) or whole body counting methods.
Dose limits are recommended by the International Commission on Radiological

Protection (ICRP) to prevent deterministic effects and limit the probability of stochastic
effects to acceptable levels.
17
(2) Area monitoring
Area monitoring system indicates the radiation status in the area and gives an early
indication of any unusual radiation fields to which the attention of the supervisors and health
physicists should be drawn. Areas handling significant amount of radioactive materials should
be provided with fixed gamma radiation monitors. In addition portable radiation survey
meters should be used for routine surveillance.
(3) Air monitoring
Monitoring of airborne activity in the laboratory and exhaust stream of ventilation

system should be carried out routinely by two methods: (a) spot sampling and (b) continuous
air monitoring.
(4) Contamination monitoring
The presence of radioactive material on the surfaces in concentration greater than the
derived working level (DWL) may ultimately result in significant uptake by operating staff.
Monitoring of surface contamination of the workplace is carried out by direct monitoring
using probes and by measuring radioactivity in swipes of the surfaces. Whenever
contamination level exceeds the limit set for specific purpose, decontamination procedure is
recommended and followed.
1.7. Packing and transportation of radioisotopes
Transportation of radioactive materials and related products is required on a regular

basis for use in medicine, industry, agriculture and research. Packages containing radioactive
materials are transported throughout the world routinely by different modes of transport, such
as rail, road, sea or air. Radioactive materials are considered as hazardous cargo (dangerous
goods) for transportation purposes. They are classified as Class 7 dangerous goods. They have
to be properly packed and labelled. Their movements are also to be documented.
1.7.1. Transport regulations
The IAEA has formulated regulations governing design requirements for different types
of packages for radioactive materials, categories of packages, procedures for testing of
packages, their storage, quality assurance requirements, documentation and emergency
response planning to deal with accident situations during transport. These regulations have
been adopted by most of the countries and also by various international organizations such as
the International Air Transport Association (IATA), International Maritime Organization
(IMO) and International Civil Aviation Organization (ICAO).
1.7.2. Types of packages
The packages generally used for transporting radioactive materials are classified into
various types: (1) excepted, (2) industrial, (3) Type A, (4) Type B, and (5) Type C packages
depending on the material’s nature and quantity.
Type A package is the most commonly used one for transport of relatively smaller
quantities of radioactive materials, FIG. 1-9. Its design is such that it is capable of
withstanding the rigors of normal conditions of transport.
18
FIG. 1-9. Typical components of a type A package.
FIG. 1-10. Type B containers for transport of radioisotopes.
19
If the radioactivity of the material to be transported exceeds the Type A limits, Type B
package which is designed to withstand the rigors of normal transport as well as severe
accidental conditions should be used, FIG. 1-10.
1.7.3. Categories of packages
Another important aspect of safe transport of radioactive material is categorizing and

labelling of the packages as per guidelines in IAEA publications. Based on the maximum
radiation level observed on the surface of the package and at 1 meter from the surface of the
package, three types of category labels are used.
These labels are also known as radioactive material transport labels, and are affixed on
two opposite sides of the package. The category label provides: radiation symbol, hazards
class number 7 for the radioactive material, transport index of the package (i.e. number
indicating maximum radiation level measured at 1 meter distance from the surface of the
package in mSv/h multiplied by 100), name and activity of the radioactive material. In
addition, it is required to indicate the complete address of the consignor.
In view of the hazardous nature of the radioactive material cargo, every package, other
than postal and excepted packages, should be accompanied by a shipping document providing
details as per IAEA guidelines.
The labels and documents are very useful for easy identification of the nature and
contents of the package, procedures to be followed for handling the package during transport
and storage, and precautions to be taken in the event of an emergency involving the package.
1.8. Conclusion
Undertaking a radioisotope production and supply programme involves infrastructural

and expertise support of many specialist agencies. These are often available within the
national nuclear establishments. The above summary has just given the outline of such
support needed. A detailed and authentic information is available in many IAEA publications
included in the bibliography. The focus of this publication is compilation of chemical
processing methods for radioisotopes produced in the reactor elaborated in the next section.
20
BIBLIOGRAPHY TO SECTION 1
IAEA Publications
Manual of Radioisotope Production, Technical Reports Series No. 63 (1966).

Radioisotope Production and Quality Control, Technical Reports Series No. 128 (1971).
Basic Principles for Occupational Radiation Monitoring, Safety Series No. 84 (1987).
Operational Radiation Protection: A Guide to Optimization, Safety Series No. 101 (1990).
Compliance Assurance for the Safe Transport of Radioactive Material, Safety Series No. 112
(1994).
Quality Assurance for the Safe Transport of Radioactive Material, Safety Series No. 113
(1994).
The Principles of Radioactive Waste Management: A Safety Fundamental, Safety Series
No. 111-F (1995).
Workplace Monitoring for Radiation and Contamination, Practical Radiation Technical
Manual No. 1 (1995).
Personal Monitoring, Practical Radiation Technical Manual No. 2 (1995).
International Basic Safety Standards for Protection Against Ionizing, Radiation and for the
Safety of Radiation Sources, Safety Series No. 115 (1996).
Radiation Protection and the Safety of Radiation Sources, Safety Series No. 120 (1996).
Characterization of Radioactive Waste Forms and Packages, Technical Reports Series
No. 383 (1997).
Management of Radioactive Waste from 99Mo Production, IAEA-TECDOC-1051 (1998).
Occupational Radiation Protection Safety Guide, Safety Standards Series No. RS-G-1 (1999).
Regulations for the Safe Transport of Radioactive Material — 1996 Edition (Revised): Safety
Requirements, Safety Standards Series No. TS-R-1 (ST-1, Rev.) (2000).
Nuclear Research Reactors in the World; September 2000, Reference Data Series No. 3,
Edition 13 (2000).
The Applications of Research Reactors, IAEA-TECDOC-1234 (2001).
International Commission on Radiological Protection (ICRP) Publications

Annual Limits on Intake of Radionuclides by Workers on the 1990 Recommendations, ICRP
Publication 60 (1991).
1990 Regulations of the International Commission on Radiological Protection, ICRP
Publication 61 (1991).
Safety Series No. 120: Recommendations of the International Commission on Radiological
Protection, ICRP Publication 26 (1996).
United Nations Publication
Recommendations on the Transport of Dangerous Goods”, Ninth Revised Edition
(ST/SG/AC. Rev. 9) UN, New York and Geneva (1995).
21
2. PRODUCTION AND PROCESSING METHODS FOR
INDIVIDUAL RADIOISOTOPES
Bromine-82 (82Br35)
Half-life : 35.30 h
81
Production scheme : Br (n, J) 82Br
Target material : Anhydrous Potassium Bromide
Decay product : Krypton-82 (stable).
Target specification and preparation
Target purity : Meets British Pharmacopoeia 1998 requirements.

Enrichment factor : nil
Impurity details : Contains 98.0–100.5% KBr with reference to the
dried substance
Isotopic composition : Non-enriched material is used
Supplier : BDH or Merck
Grade : Analytical reagent grade
Irradiation parameters, specific activity and total yield at EOI
Reactor used : HIFAR, Lucas Heights, Australia

Assembly : Hydraulic tube with conveyor unload
Capsule details : Potassium bromide starting material is housed in a
standard silica ampoule, sealed by glass blower. The
silica ampoule is then placed in a screw top
aluminium or titanium inner can, which in turn is
placed in a weld sealed aluminium or titanium outer
can
Target mass : 93 mg KBr/capsule
Target preparation : Dry at 150°C for 4 h
Reactor neutron flux : ~ 5 × 1013 n/cm2/s (thermal)
Irradiation time : 30 hours
Cooling period : 24 hours
Expected activity : 16.65 GBq (450 mCi) 82Br/~6 GBq/g Bromine
element
Processing facility
This material is processed inside a hot cell.
Analysis of raw materials, reagents and chemicals required for processing
Water for injections BP
This material is purchased as such and meets British Pharmacopoeia 1998 requirements.
The above procedure was provided by:

Australian Nuclear Science and Technology Organisation,
Radiopharmaceutical Division,
Operations-Lucas Heights, Australia.
25
Cation exchange resin
Dowex 50-W-X8 size 50 to 100 mesh or approved equivalent.
Sodium chloride intravenous infusion BP
1.0 M Sodium hydroxide solution
This material is prepared by making a ~4% w/v solution of sodium hydroxide in Water for
Injections BP. The solution is filtered through a 0.22 µm membrane filter into sterile clinbritic
vials. The solution is standardized by titrating against standardized 1.0 M hydrochloric acid,
using phenolphthalein as an indicator. The solution is approved for use with a concentration
of 0.9–1.1 M NaOH. Material approved for use is stored under refrigeration, and has an
expiry period of 3 months.
1.0 M Hydrochloric acid solution
This material is prepared by diluting concentrated Hydrochloric Acid AR grade with Water
for Injections BP. The solution is filtered through a 0.22 µm membrane filter into sterile
clinbritic vials. The vials are then autoclaved for 6 minutes at 132°C. The solution is
standardized by titrating against standardized 1.0 M sodium hydroxide solution, using
phenolphthalein as an indicator. The solution is approved for use with a concentration of 0.9–
1.1 M HCl. Material approved for use is stored under refrigeration, and has an expiry period
of 6 months.
Exchange resin column
The preferred column is a 10 or 20 mL disposable plastic syringe body with a silica wool wad
pushed into the body. Alternatively, a glass column can also be used. The column is prepared
by weighing 5–10 g of cationic exchange resin into a beaker and covering with Water for
Injections BP, and allowing to hydrate for 5 minutes. The water is decanted then the process
repeated another 2 times. The cationic exchange slurry is then poured into the column over
the silica wool to a level of ~10 mL. The column is then rinsed with a minimum of 50 mL of
Water for Injections BP.
Chemical processing procedure
1. All equipment is transferred to the manufacturing cell before commencing.

2. Remove the irradiated potassium bromide from the silica target ampoule, and dissolve in
3 mL of water for injections BP.
3. Pour the dissolved bromine target through the prepared exchange resin column. Collect
the solution in a receiving vessel containing 0.8 mL of 1.0 M sodium hydroxide. Rinse
the preparation vessel with several small volumes of water, adding each washing to the
column until an elution volume of 15 mL is reached.
4. Mix well and measure pH by placing a drop of the solution onto pH paper via pipette
without making contact with paper to pipette. Adjust pH to 6–8 with 1.0 M NaOH or 1.0
M HCl if required. Make up to 20 mL with Sodium Chloride Intravenous Infusion BP.
5. Measure the activity at calibration of 1 mL of solution, and calculate the volume of
Sodium Chloride Intravenous Infusion BP needed to make the required quantity of dilute
stock (40 MBq/mL at calibration).
26
6. Add the required calculated volume and mix well. Then filter diluted stock through a 0.22
µm membrane filter into a sterile vial.
7. Using a clean pipette dispense the required volumes into sterile vials. Seal then autoclave
the vials at 132°C for 6 minutes.
8. When autoclaving is complete, place the vials into 25 mm lead pots.
Dispensing, assay and quality control
Radioactive concentration
The radioactive concentration must be 36–44 MBq/mL 82Br at the calibration time and date.
Measure a sample in an ionization chamber that has been calibrated to measure bromine-82.
Ac = Ame-0.019t
where
Ac is the activity at the calibration date and time,

Am is the activity at the measurement date and time,
0.019 is the decay factor based on half-life of 35.4 h,
t is the difference in hours between measurement time and calibration time.
Radionuclidic purity
82
The radionuclidic purity is acceptable if a gamma spectrum analysis identifies Br, and all
other gamma emitters are <0.05%.
A sample of bromine-82 solution is put in a sealed container, and placed centrally on the
detector of a gamma spectrometer. The data must be collected over the 2000 keV range for at
least 1000 s.
The product is identified from the following major J-energy peaks:
554, 619, 698, 777, 828, 1044, 1317, and 1475 keV.
Potassium-42 which has a J-energy peak at 1525 keV must not be detected.
The sample is kept for 24 h after irradiation, and before dispensing, to ensure that the
bromine-80m content is less than 2%. (80mBr major J-energy peaks: 511, 617 and 666 keV)
pH
The pH must be between 4.0–10.0. Measure the sample on a pH meter or using a suitable
narrow pH range paper.
Isotonicity
The isotonicity is measured on a standardized osmometer. The value obtained must be

between 240 and 360 milliosmoles/kg. The measurement is made on a decayed sample.
27
Final product specification
Dosage form : The dosage form is a sterile, isotonic and non-

pyrogenic solution for intravenous injection
containing radioactive bromine-82 as sodium
bromide/chloride.
Formulation : Each vial contains 80 MBq of bromine-82 at
calibration in 2 mL of sodium chloride/bromide.
Physical form : 2 mL of a colourless aqueous solution contained in a
10 mL serum vial.
pH : 4–10.
Specific activity : ~6 GBq/g bromine element at calibration.
Radionuclidic purity : All other gamma emitters are <0.05% at calibration.
Radiochemical purity : ~100% bromine present as bromide ions.
Radioactive concentration : 36–44 MBq/mL at calibration.
Radioactive content : 72–88 MBq bromine-82 at calibration.
Chemical purity : Heavy metals <10ppm.
Isotonicity : The solution has an osmotic pressure of 240–
360 milliosmoles/kg.
Sterility : The product is sterile.
Pyrogens : The product is pyrogen free.
Expiry : 96 h after calibration time and date.
Storage : Store at ambient temperature.
Cell cleanup : All waste is removed from the cell and placed into the
appropriate shielded waste receptacles. Solid waste is
stored separate to liquid waste. If required, equipment
in the cell is allowed to decay prior to cleaning the
cell. The cell surfaces are then cleaned by swabbing
with lint free cloths liberally doused with isopropanol
or ethanol.
28
Calcium-45 (45Ca20)
Half-life : 162.61 ± 0.09 d

44
Production scheme : Ca (n,J) 45Ca
Target material : CaCO3 (G.R./A.R.) (E.M.)
Decay product : Scandium-45
Nuclear reactions and yield
Reaction Isotopic Cross- Activity of element at Secondary reactions

abundance section 1012 n/cm2/s and properties of
of nuclide% barn One Four Satu- nuclide formed
week weeks ration
44 46
Ca (n,J) 2.086 0.88± 7 MBq 27 MBq 237 MBq Ca(n,J) 47 Ca
45
Ca 0.05 (0.189 (0.726 (6.4 mCi)/g Half-life: 4.536
mCi)/g Ca mCi)/gCa Ca days
Isotopic
Abundance:
0.004%
V= 0.74 ± 0.07 b
45
Sc(n,p) 45Ca 100 <10-9 b 45
Sc (n,J) 46Sc
Half-life: 83.79
days
V =27.2 ± 0.2 b
Type of decay and energy : E (MeV) 0.257 (Emax) (100%)
Target 2 × 5 g of CaCO3 (EM) (GR/AR).
Container Standard 1S aluminium can 22 mm dia and 44 mm ht. (cold

welded).
Reactor used Heavy water moderated 100 MW DHRUVA or 40 MW Cirus

reactor provides the necessary irradiation facility.
Duration 6 months.
Flux 4 × 1013 n/cm2/s.

Production yield 400–1200 MBq (10–30 mCi/g of CaCO3.
Sp. Activity >1200 MBq (30 mCi)/g of Ca.
Reagents
All the reagents used are of GR/AR grade.

M. Ananthakrishnan,
Board of Radiation and Isotope Technology,
Department of Atomic Energy, Mumbai, India.
29
Type of facility for processing
Standard fumehood 4 feet × 3 feet × 6 feet with local 2 inch lead shielding.
Chemical process
The irradiated CaCO3 can is cooled for one month to allow the decay of short lived 47Ca
activity. The can is opened and then irradiated target is transferred to a beaker. Approx. 30
mL concentrated HCl is added slowly to dissolve the CaCO3. The solution is boiled to expel
CO2. About 1 g iron carrier as FeCl3 in solution is added to the beaker. Sufficient quantities of
ammonium chloride and ammonium hydroxide are added to it and iron hydroxide is
precipitated which carries the scandium-46 impurity activity. The precipitate of iron
hydroxide (Fe (OH)3) is separated by filtration. Filtrate is heated to reduce the volume and
carrier iron precipitation is repeated thrice to eliminate impurities. The filtrate is boiled.
Volume of the solution is reduced and a solution of saturated ammonium carbonate is added
to precipitate calcium as calcium carbonate. The precipitate is filtered, washed with dilute
solution of ammonium carbonate and double distilled water and finally dissolved in dilute
HCl. The solution is boiled to expel CO2 and filtered to a clear solution.
Assay and quality control
Activity is assayed by liquid scintillation counting.
Radionuclide purity is determined by beta ray absorption analysis and by confirming absence
of gamma emitting impurities in gamma ray spectrum.
Calcium content is determined by volumetric method.
Characteristics of final solution
Radiochemical form Calcium chloride in HCl solution.

Radioactive concentration 37–185 MBq/mL (1–5 mCi/mL).
Radiochemical purity >99% as sulphate.
Radionuclide purity >99%.
Specific activity >1 GBq/g Ca.
Code Ca-2.
Appearance A clear colourless solution.
30
Carbon-14 (14C6)
Half-life : 5730 ± 40 a
14
Production and decay scheme : N7 + 1n0o 14C6 + 1p1 V = 1.81 b
Type of decay and energy : E (keV) 156.478 ± 0.009
Target material : AlN
Flow chart of the operation and procedures
The purity of AlN target powder is not less than 95%. The AlN powder has a particle size
between 0.007 to 0.1mm, and contains 12C of less than 0.01%.
AlN synthesis
The synthesis apparatus is illustrated in Fig. 1. 100g Al powder (t99.999%) and 5g

KHF2(A.R.) is mixed in a Ni boat(2), and the Ni boat is put into a quartz tube(3) in an electric
resistance furnace(4) which is flowed through with N2 gas at a flow rate of 2 L/min. The
furnace is heated up to 820oC. Airflow at a flow rate of 300mL/min is used to control the
reaction. After reaction for 3 hours, the AlN product is cooled down to room temperature.

Jiang B., Cheng Z., Li M.,
Nuclear Power Institute of China,
P.O.Box 436, Chengdu 610041, China.
31
FIG. 1. Illustration of the AlN synthesis apparatus: 1—gas mixing chamber; 2—Ni boat; 3—quartz
tube; 4—electric resistance furnace; 5—buffer bottle; 6—glass beaker
Target capsule preparation
Target capsule: 14g AlN powder is added into a 305 Al alloy can of 10mm in inner diameter
and 100mm in length. Two Al plates are put on the top of AlN powder. Air in the can is
replaced with N2 gas and the can is argon arc welded.
Target assembly: Eight target capsules are put into a 305 Al alloys tube and the tube is argon
arc welded.
The target is irradiated in the beryllium channel ()=20mm) of the High Flux Engineering
Test Reactor at the Nuclear Power Institute of China for 180 days. The neutron flux is
12 × 1014 n/cm2/s. Specific activity is over 185 MBq/gAlN and the typical total yield of one
target assembly at EOI is 21GBq.
The hot cell used for target assembly cutting is 2200 × 1800 × 2400(length × width × high),
shielded with concrete of 500mm in thickness, and equipped with a pair of MJ-2 model
master-slave manipulators.
The glove box used for target capsule cutting is shielded with cast iron of 75mm in thickness.
The glove box used for chemical processing is shielded with stainless steel of 3 mm in
thickness.
Analysis of AlN powder
Size: assayed by standard sieve.
AlN content: 100 mg AlN is dissolved in a Sn(II)-H3PO4 solution(2g SnCl2 is dissolved in

30 mL concentrated H3PO4) and mixed with excess 40% NaOH, and then heated. The NH3
formed is absorbed in 50 mL saturated boric acid, and 0.1 mol/l HCl is used for titration of the
solution. The AlN content was calculated, as follows:
C=2.93 × (V1-V2) × T/W × 100%
32
Where
C is AlN content(%),
V1 is the volume of HCl used (mL),
V2 is the volume of HCl used in blank titration (mL),
W is the sample weight(g) and T is the titer of HCl to N.
C content in AlN: AlN is dissolved in a 40% NaOH solution and CH4 formed is oxidized to
CO2 by heat CuO. Then CO2 is determined with GC. The LOD of the method is 20ppm, and
the relative standard deviation is 10%.
H2SO4, H3PO4 used are of MOS grade, while CrO3, KIO3, NaOH, Ba(OH)2 and C2H5OH were
of G.R. grade.
100 mL oxidant (5g KIO3 and 25g CrO3 dissolved in 333 mL H2SO4 and 167 mL H3PO4
solution at 150oC) is added into the reaction flask(1). The reaction flask is heated to 130oC
and the system is flowed with N2 gas for 30min. Then the reaction flask was heated to 150oC,
while the temperature of CuO oven is kept at 750oC. After reaction for 4 hours, 9 mL
saturated Ba(OH)2 solution is added into 2.5 mol/l NaOH adsorption solution (11). Ba14CO3
precipitated is filtered by the funnel (12) and washed with CO2-free water and CO2-free ethyl
alcohol and finally dried by infrared lamp in an N2 atmosphere. The processing system is
shown in Fig. 2.
FIG. 2. System of chemical processing of 14C production: 1-reaction flask; 2-heater; 3-

sampling funnel; 4-thermometer; 5-reflux condenser;6-cleaner; 7-glass wool; 8-quartz tube
(CuO); 9-electric resistance furnace; 10-glass wool; 11-14CO2 adsorption vessel; 12-G-5
filer; 13-buffer bottle; 14,14’-water; 15–18-vaccuum valve.
33
Specific activity assay
1.0 mg Ba14CO3 is put into a 10 mL beaker and 0.5 mL EDTA solution (30g/l, PH=13) is
added. After Ba14CO3 is dissolved, the solution was diluted to 50 mL with 1 mol/l NaOH
solution. About 10mg of the solution is taken and weighed, and the radioactivity is measured
by scintillation spectrometry. The specific activity is calculated by the following equation:
Asp=N. K/(E. M)
where
Asp is the specific activity(Bq/mg),

N is count(cps); M is the weight of the solution taken from BaCO3 sample solution(g),
K is the ratio of the weight of BaCO3 sample solution to M,
E is the detection efficiency.
Radionuclidic purity: is determined by a HPGe J spectrometry.
Final product specification for use
Physical observations: the product is a white powder.

Radionuclide identification: by comparison of the standard spectrum of 14C with that of the
product. The ratio of radioactivity of E impurities to that of 14C should be less than 0.1%.
Practical experience gained
1. The 12C content in AlN powder must be controlled under 0.01%.

2. The processing system and the reagents should be purified.
BIBLIOGRAPHY
ANAL. CHEM. 44 (1972) 887.

ATOMPROXIS. 14 (1968) 491–494.
FUCCILLO, D.A.JR., ORNL-3633, Oak Ridge National Laboratory, Tennessee (1964) 41.
ISOTOPENPROXIS. 8 (1972).
34
Chromium-51 (51Cr24)
Half-life : 27.70 d.
50
Production scheme : Cr (n, J) 51Cr V = 15.9 ± 0.2 b
Target material : Chromium metal
Type of decay and energy : 100% EC o 51
Decay product : Vanadium-51 (stable)

Target purity : 99.9% chromium
Enrichment factor : Nil
Impurity details : Total radioisotopic impurities in activated sample
should be <0.1%.
Isotopic composition : A sample is activated and processed as per
instructions below, then analysed via gamma
spectroscopy. After production, only peaks for 51Cr
should be detected. After a 54 d decay period, the
following impurities should be identified and
quantified relevant to initial 51Cr:
60
Co <0.001%
59
Fe <0.005%
182
Ta <0.005%
Solubility : Must readily dissolve in 8 M hydrochloric acid.
Insoluble in nitric acid and aqua regia. Note: The
dissolution of “Specpure” grade chromium is
unacceptably slow
Supplier : Various metal industries
Grade : High purity grade
Reactor used : HIFAR, Lucas Heights, Australia

Assembly : Hydraulic tube with conveyor unload
Capsule details : Chromium metal is placed in a screw top aluminium
or titanium inner can, which in turn is placed in a
screw top aluminium or titanium outer can
Target mass : 1 g chromium metal
Target preparation : Metal is finely ground before irradiation, degreased
with acetone
Reactor neutron flux : ~ 5 × 1013 n/cm2/s (thermal).
Irradiation time : 24 d
Cooling period : N/A
Expected activity : >30 GBq 51Cr/g chromium element

35
Processing facility
This target material is processed inside a Hot Cell to make the stock Chromium (51Cr)
Chloride solution. The Chromium (51Cr) Edetate Injection BP is manufactured in a class 350
clean room (AS 1386), which contains a class 3.5 (100) laminar flow cabinet (AS 1386.5–
1994) for dispensing.
Sodium chloride intravenous infusion BP
This material is prepared by making a ~4% w/v solution of sodium hydroxide in Water for
Injections BP. The solution is filtered through a 0.22 µm membrane filter into sterile clinbritic
vials. The solution is standardized by titrating against standardized 1.0 M hydrochloric acid,
using phenolphthalein as an indicator. The solution is approved for use with a concentration
of 0.9–1.1 M NaOH. Material approved for use is stored under refrigeration, and has an
expiry period of three months.
EDTA (diSodium Edetate)
Inactive chromium chloride solution (20 mg/mL Cr)
The solution is made by dissolving chromium metal (same as irradiation target) in

hydrochloric acid (~10 mL of concentrated hydrochloric acid and 1 mL of water for every
gram of metal). The solution is evaporated to NEAR dryness and then redissolved in Water
for Injections BP to give a concentration of 20 mg Chromium/mL. The solution is filtered
through a 0.22 µm membrane filter into sterile vials. Material approved for use is stored under
refrigeration, and has an expiry period of six months.
Hydrochloric acid
Preparation of stock chromium (51Cr) chloride solution

2. Add the irradiated target material to a 50 mL beaker, and slowly add 10 mL of
hydrochloric acid. Heat on a hotplate until dissolved then evaporate to dryness. Try to
avoid spluttering.
3. Dissolve residue in 10 mL of Water for Injections BP and evaporate to dryness.
4. Redissolve residue in 20 mL of Water for Injections BP and mix well.
36
5. Filter through a 0.45 µm membrane filter into a sterile 30 mL vial.
6. Cap, seal and autoclave the vial at 132°C for 6 minutes. This stock solution can then be
stored in a shielded storage area until required for manufacture of Chromium (51Cr)
Edetate Injection BP.
Preparation of chromium (51Cr) edetate injection BP
1. All equipment is transferred to the manufacturing clean room before commencing.

2. Calculate the required reagent quantities as follows:
EDTA (g) = 1.09 V/100
where V = nominal batch size (mL)
Water for Injections BP (mL) = 0.45 V
Volume of stock Chromium (51Cr) Chloride solution (mL) = 8.8 V/A
where A = stock solution activity at calibration (MBq/mL)
Volume of Inactive Chromium Chloride Solution (mL) = B/C
where B = 0.29 V–D
C = inactive chromium chloride solution concentration (mg/mL)
D = 8.8 V/E
E = stock solution specific activity at calibration (MBq/mg).
3. Dissolve required amount of EDTA in required amount of Water for Injections BP in a
250 mL round bottom flask.
4. Add the required amounts of stock chromium (51Cr) chloride solution and inactive
chromium chloride solution to the flask.
5. Reflux the flask contents under gentle boiling for at least 30 min; observe that the vapour
does not rise above the water level in the condenser. After refluxing, allow to cool to
ambient temperature.
6. Adjust the pH to ~5.5 using 1 M sodium hydroxide solution and a dedicated pH meter.
7. Dilute the solution with Sodium Chloride Intravenous Infusion BP, so that the final
solution has an activity concentration of 7.2–8.8 MBq/mL at calibration. Confirm by
measuring 1 mL of diluted stock in an ion chamber.
8. Transfer the diluted solution to a laminar flow cabinet for dispensing.
9. Using a clean pipette, fitted with a 0.45 µm membrane filter and a 0.22 µm membrane
filter in tandem, dispense the required volumes into sterile vials. Seal then autoclave the
vials at 132°C for 6 minutes.
When autoclaving is complete, place the vials into lead pots containing absorbent material.
The radioactive concentration must be 7.2–8.8 MBq/mL 51Cr at the calibration time and date.
Measure a sample in an ionization chamber that has been calibrated to measure chromium-51.
Ac = Ame-0.025t
where
Ac is the activity at the calibration date and time,
Am is the activity at the measurement date and time,
0.025 is the decay factor based on half-life of 27.7 d,
t is the difference in hours between measurement time and calibration time.
37
51
The radionuclidic purity is acceptable if a gamma spectrum analysis identifies Cr, and no
other gamma emitter is detected.
A sample of chromium-51 solution is put in a sealed container, and placed centrally on the
detector of a gamma spectrometer. The data must be collected over the 2000 keV range for at
least 1000 s. The product is identified from the major Ȗ-energy peak at 320 keV.
Radiochemical purity
The solution is analysed by paper electrophoresis, using 0.005 M hydrochloric acid as the
mobile phase. The strips are marked with an origin 3 cm from the anode, and one strip is
spotted with the dilute solution, and a second strip is spotted with a chromium-51 sample.
These strips are electrolysed for 35 min at 1000 V. The strips are dried, then cut into 1 cm
segments, which are counted in a Ȗ well counter.
The chromium (51Cr) edetate species is found approximately 0–5 cm on the cathode side from
the point of application, and must be greater than 95% of the total radioactivity. The Cr3+
species is found approximately 10–13 cm on the cathode side from the point of application,
and must be less than 0.5% of the total radioactivity.
pH
The pH must be between 3.5–6.5. Measure the sample on a pH meter.
Isotonicity
The isotonicity is measured on a standardized osometer. The value obtained must be between
240 and 360 milliosmoles/kg. The measurement is made on a decayed sample.
Limit test for EDTA
Prepare the following reagents :

EDTA standard 10.9 mg/mL : 10.9 g of disodium EDTA in 100 mL of water.
EDTA standard 15 mg/mL : 15 g of disodium EDTA in 100 mL of water.
0.5% potassium chromate
solution : A 0.5% w/v solution of potassium chromate AR
grade made in water.
Reducing agent : Dissolve 2.473 g of arsenious oxide and 1.75 g of
sodium hydroxide in 75 mL of water. Carefully
neutralize with acetic acid and dilute to 150 mL with
water. To this solution, slowly add 100 mL glacial
acetic acid with constant mixing.
Into 3 small test tubes add : (a) 0.1 mL of prepared Chromium (51Cr) Edetate
Injection BP .
(b) 0.1 mL of EDTA standard 10.9 mg/mL.
(c) 0.1 mL of EDTA standard 15 mg/mL.
To each tube, add 1 mL of 0.5% potassium chromate solution and mix. Carefully add 1 mL of
the reducing agent, then heat the tubes in boiling water for 5 minutes. Compare the tubes
against a white background. The colour in the Chromium (51Cr) Edetate Injection BP sample
38
tube should be equivalent to the EDTA standard 10.9 mg/mL, and should not be darker than
the EDTA standard 15 mg/mL.
Limit test for chromium
Prepare a standard chromium edetate solution (1% w/v Cr) as follows:

Dissolve 0.96 g of chromium (III) potassium sulphate AR grade and 2.87 g of sodium edetate
in 50 mL of water. Boil for 10 minutes, cool, adjust to pH 3.5–6.5 with 2 M sodium
hydroxide and dilute to 100 mL with water.
The absorbance measured at 560 nm for the Chromium (51Cr) Edetate Injection BP sample is
not more than the standard chromium edetate solution.
Dosage form : The dosage form is a sterile, isotonic and non-

pyrogenic solution for intravenous injection
containing radioactive chromium-51 as chromium
edetate. The solution conforms to the British
Pharmacopoeia 1998 requirements for Chromium
(51Cr) Edetate Injection BP.
Formulation : Each vial contains 8 MBq of chromium-51 at

calibration, ~0.3 mg of chromium element and ~10
mg of EDTA in 1 mL of solution.
Physical form : 1 mL of solution contained in a 3 mL serum vial.

PH : 3.5–6.5.
Specific activity : >30 GBq 51Cr/g chromium element at calibration.
Radionuclidic purity : No other gamma emitters are detectable at calibration.
Radiochemical purity : <0.5% radioactivity present as chromic ions; >95%

radioactivity present as chromium edetate species.
Radioactive concentration : 8 MBq/mL at calibration.

Radioactive content : 8 MBq chromium-51 at calibration.
Isotonicity : The solution has an osmotic pressure of 240–360

milliosmoles/kg.
Limit test for EDTA : 10.9 mg/mL and <15 mg/mL.

Limit test for chromium : <0.1% w/v Cr.
Sterility : The product is sterile.
Pyrogens : The product is pyrogen free.
Expiry : 31 d after calibration time and date.
39
in the cell is allowed to decay prior to cleaning the
cell. The cell surfaces are then cleaned by swabbing
with lint free cloths liberally doused with isopropanol
or ethanol.
It has been found beneficial during the reflux step to use a specially designed condenser that
is filled with cold water and ice.
BIBLIOGRAPHY
COMMISION OF THE EUROPEAN COMMUNITIES, Cr-51 EDTA (injection), 111/3140/

93-EN (1993).
40
Cobalt-58 (58Co27)
Half-life : 70.86 ± 0.07 d

58
Production scheme : Ni (n,p) 58Co
Targe material : Nickel metal
Type of decay and energy : 0.4746 MeV (14.9%) positron

0.81 MeV gamma (99.45%)
Decay product : Nickel-58
High purity nickel metal targets (i.e. 68.27% natural abundance) are used. The projected
production yields of cobalt-58 from irradiation of nickel as a function of irradiation time at
various thermal neutron flux values are shown in Fig. 1.
FIG. 1. Calculated production yields of cobalt-58 by neutron irradiation of nickel targets as a

function of irradiation time at various thermal neutron flux values.
An adequately shielded hot cell or other shielded facility, dependent upon the levels of
activity handled, is required for processing the irradiated targets.

M. Du and F.F. Knapp, Jr.,
Nuclear Medicine Program, Oak Ridge National Laboratory,
Oak Ridge, Tennessee 37830-6229, United States of America.
41
Processing of cobalt-58 from nickel targets (from ORNL Radioisotopes Procedure Manual,
ORNL-3633, 1964)
1. The following equipment should be prepared: Hot off-gas scrubber unit, quartz
evaporation dish, five 150 mL Pyrex beakers, 40 mL ion exchange column and 100 mL
product bottle.
2. Open irradiation can and remove target from ampule.
3. Wash crushed quartz capsule and NiO into evaporation dish with 12 M HCI.
4. Heat to dissolve NiO using hot off-gas scrubber assembly. Add additional HCI if
necessary to dissolve sample.
5. Dissolve NiCl2.6 H2O crystals in 12 M HCl. Use approximately 100 mL of 12 M HCl per
gram of nickel and heat if necessary to produce clear solution.
6. Evaporate NiCl2 solution to dryness and fume with 12 M HCl. Care should be taken to
avoid conversion of the chloride to oxide.
7. Prepare a 100-mesh Dowex 1 resin column for 58Co separation conditioned with 12 M
HCl. Resin volume should be ~70 mL per gram of nickel in solution.
8. Pass NiCl2 solution through the resin column and rinse column with 12 M HCl until
green color is eluted. Cobalt-58 remains on the column.
58
9. Elute ion exchange column with distilled H2O and check effluent for Co activity to
determine efficiency of removal from column.
10. Collect effluent in beaker and evaporate to near dryness under hot off-gas scrubber
assembly.
11. Fume residue with 16 M HNO3.
12. Fume with 12 M HCl to destroy any organic compounds which may be present and to
remove the Nitric acid.
13. Dissolve in 50 mL of 1 M HCl and transfer to product bottle.
14. Sample and analyse for:
Molarity of HCl
58
Co concentration
Total solids.
The final product is analysed by gamma spectroscopy.
42
The final product should be analysed by gamma spectrocopy and is provided as the chloride
in HCl solution.
Because of the low 0.092 barn production cross-section, only low yields of cobalt-58 are
produced by this route. At ORNL, yields of 400 mCi were produced after one year irradiation
14
of a one gram target at a flux of 2 × 10 n/cm2/s.
BIBLIOGRAPHY
OAK RIDGE NATIONAL LABORATORY, Radioisotopes Procedures Manual, ORNL-

3633, UC-23-Isotopes — Industrial Technology, TID-4500 (30th ed.), Tennessee (1964).
43
Cobalt-60 (60Co27)
Half-life : 5.2714 ± 0.0005 a

59
Nuclear reaction : Co (n, J) 60Co V = 37.18 ± 0.06 (m + g)
Target material : Metallic cobalt
Decay product : Nickel-60
Type of decay and energy (MeV)
Beta (E) 1.49 (0.011%) Gamma (J) 1332.5 keV (99.9856%)

(Emax) 0.31 (99.925%) 1173.2 keV (99.9736%)
60m
Co : 10.467 min
99.76% IT
0.24% E-
Production flow chart
Preparation of target Target Target Activity

for irradiation irradiation disassembly measurement
Source Source Cutting of Transport

welding assembly pencils to hot cell
Calibration Quality Dispensing

control
Target material: metallic cobalt, covered with nickel.
Specific purity: > 99.7% of Co-59

The cobalt is in form of metallic cylinders (slugs with 6.4 mm of diameter and 12.7 mm or
25.4 mm of length) or in form of pellets (1 mm of diameter and 1 mm of length).
The slugs and pellets encapsulated inside Zircalloy 4 tubes (called pencils) with welded seal
caps at both ends.

Ezeiza Atomic Centre,
Comisión Nacional de Energía Atomica,
Buenos Aires, Argentina.
44
1. Reactor used and which assembly:
CANDU 6 Reactor (pressure tubes, heavy water moderated)

Gross power: 648 Mew
Assembly: Adjuster/absorber Rods (Co-59), mechanical assembly
Working temperature (moderator temperature): 50/60ºC
Working pressure: almost atmospheric pressure.
2. Capsule details (Fig. 1):
Stringing a number of cobalt bundles onto a tie rod makes up the cobalt adjuster element of
the CANDU reactor. The bundles consist of cobalt pencils arranged circunferentially around a
central rod, and held between two end plates; these are counter bored to receive the cobalt
pencils. The rod and the plates are made of Zircalloy. Twenty-one cobalt adjuster elements
are placed in the reactor.
FIG. 1. Cobalt target assembly.
3. Mass of target:
The mass of each pencil varies from 52 g to 80 g depending of the length of the pencils and
the form of the cobalt (slugs or pellets).
4. Reactor irradiation parameters:
Irradiation Flux (average value): 2 × 1014 n/cm2 /s (thermal neutrons).

Irradiation Period: 18, 24 or 36 months. This period range depends of Planned Outage
schedule and marketing conditions of specific activity requested by CNEA.
45
5. Specific activity achieved:
The specific activity varies between a range of 4.5–9.5 TBq (120–250 Ci)/g depending of
Planned Outage schedule and marketing conditions.
POOL in Embalse Nuclear Power Plant for target disassembly and the calibration underwater
of the bundles of pencils with Co-60.
PRODUCTION HOT CELL in Ezeiza Atomic Center for the fabrication of the sealed
sources.
Thickness: 1,3 m of heavy concrete.
Internal dimensions: 3 m × 3 m × 4 m of height.
Internal equipment: bridge-crane, containers for transitory storage, TIG electronic
welding machine.
3. QUALITY CONTROL HOT CELL for the quality control of all the sealed sources and
the calibration of the sources used in teletherapy.
Thickness: 1 m of heavy concrete
Internal dimensions: 2 m × 2 m × 3,3 m of height.
FIG. 2. Hot cell for Co-60 handling.
4. POOL OF TRANSFER for the calibration of the industrial sealed sources and the loading
of the sources in transport containers.
Test method by radioactive means
Immersion test (hot liquid) in agreement with ISO 9978 (5.1.1)/ ISO: TR 4826 (2.1.3).
Dry wipe test in agreement with ISO 9978 (5.3.2)/ ISO: TR 4826 (2.1.2).
46
Approval criteria: If the activity detected does not exceed 0,2 kBq (5 nCi) in agreement
with ISO 9978 (5.1.5 and 5.3.3).
Test methods by non-radioactive means
Helium test in agreement with ISO 9978 (6.1.1)/ISO: TR 4826 (2.2.4) .
For calibrating sealed sources the following procedures are applied
Bundles: Radiation measurement procedure for underwater measurement of cobalt-60

bundles.
Sealed Source for teletherapy: ICRU-Report 18
Sealed Source for Industrial Use: in air or in water, ICRU-Report 18.
For welding sealed sources
The sources has two stainless steel AISI 316-L encapsulations sealed by TIG Electronic
Welding, in agreement with:
ASTM-A-240
ASTM-A-312
ASTM-A-380
ASME-SECC IX-DIV 1
ASME-SECC V-DIV 1.
The transport of high activities of Cobalt 60 is made with transport packaging in agreement
with the: "Regulations for the safe transport of radioactive materials", 1985 Edition (As
Amended 1990), Safety Series Nº 6 of the International Atomic Energy Agency (IAEA).
FIG. 3. Dimensions of different Co-60 sources.
47
FIG. 4. Containers for Co-60 and their handling in Argentina.
48
FIG. 5. Containers for Co-60 and their handling in Argentina (cont.).
49
1. Description of the special form radioactive material (Fig. 3).
1.1 Co-60 Pencil has one zircaloy encapsulation sealed by TIG. Dimensions: total length
212,73 mm or 285,2 mm; external diameter 8,05 mm.
1.2 FIS 60–04 (Industrial Source) has an internal Cobalt-60 pencil and two external stainless
steel AISI 316-L encapsulations sealed by TIG. Dimensions: total length 296 mm or 229
mm; external diameter 11,3 mm.
1.3 FIS 60–03 (Industrial Source) has two internal Cobalt-60 pencils (length 212,73 mm) and
an external stainless steel AISI 316-L encapsulation sealed by TIG. Dimensions: total
length 451,5 mm; external diameter 11,1 mm. Classification ISO 2919 E 66646.
1.4 FSM 60–03 (Teletherapy Source) Cobalt-60 is in the form of slugs or pellets has two
stainless steel AISI 316-L encapsulations sealed by TIG. Dimensions are total length
36,5 mm; external diameter 23,5 mm. Classification ISO 2919 E 53524.
The National Commission of Atomic Energy of Argentina (CNEA) produces Co-60 sealed
sources from 1981, for teletherapy, industry and research.
Since then, the sources have been exported to different countries all over the world.
With the production Co-60 and important experience has been obtained, especially in the
handling of high activities.
50
Copper-64/Copper-67 (64Cu29, 67Cu29)
64
Half-life : Cu – 12.7 ± 0.02 h
67
Cu – 61.83 ± 0.12 h
63
Production scheme : Cu (n,J) 64Cu V = 4.5 b
67
Zn (n,pJ) 67Cu
Target material : High purity copper and/or zinc targets
Decay energy : Copper 64
E (MeV) E+ (MeV) EC (MeV)

0.5787 (39%) 0.653 (17.4%) 43%
Copper 67
E (MeV) Gamma (MeV)

0.391 (57%) 0.1845 (48.7%)
0.483 (22%) 0.0933 (16.1%)
0.576 (20%) 0.0912 (7%)
0.182 (1%)
Copper-64 is one of the few neutron rich positron emitting radioisotopes which can be
reactor-produced by a simple radiative (n,J) reaction with relatively high specific activity. As
an alternative, carrier-free copper-64 can also be reactor-produced (n,p) by neutron irradiation
of enriched zinc-64 targets. Although the preferred route for production of copper-67 is via
spallation using an accelerator (Mirzadeh, et al., 1986), low levels of carrier-freee copper-67
can be produced in a nuclear reactor by the (n,p) reaction via irradiation of the very expensive
enriched zinc-67 targets. Three typical procedures are provided describing the processing of
copper targets by direct dissolution of copper-63 targets, solvent extraction of solutions
prepared from neutron-irradiated enriched zinc targets and more recent electrochemical
techniques for processing of zinc targets to obtain carrier-free copper-64 and copper-67.
Irradiation parameters, specific activity and yotal yield at end of irradiation
For direct production of copper-64, high purity enriched copper-63 targets (i.e. 63.9% natural
abundance) are used. The projected production yields of copper-64 from irradiation of
copper-63 as a function of irradiation time at various thermal neutron flux values are shown in
Fig. 1. For production of copper-67, highly enriched zinc-67 targets (i.e. >94%) are required.

S. Mirzadeh and F. F. Knapp, Jr.,
Nuclear Medicine Programme,
Oak Ridge National Laboratory,
51
FIG. 1. Calculated production yields of copper-64 by neutron irradiation of enriched copper-63
targets as a function of irradiation time at various thermal neutron flux values.
Processing of copper-64 from enriched copper-63 targets (from ORNL nuclear medicine
procedure # 24)
1. The quartz ampule is removed from the aluminum capsule using tubing cutter and vise
and examine ampule to determine if it has been broken. If unbroken, place the ampule on
cloth wipe and rinse with 1 M HCl and then blot dry. If broken, proceed to Step 5.
2. Transfer the quartz ampule to a plastic break tube, stopper, and crush using vise. Transfer
the content of the break tube to a 125 mL flask and add sufficient volume of 4 M HCl and
transfer to flask.
3. Begin evaporation of the liquid on a hot plate adjusted to keep the temperature just below
the boiling point. Shake the flask occasionally to insure that the quartz pieces have been
wetted. Continue the evaporation to incipient dryness and then allow the flask to cool.
4. Transfer the 64CuCl2 residue in the flask to a 15 mL product bottle using incremental
portions of 0.1 M HCl. Be sure the quartz fragments are rinsed after each addition of
acid.
5. Rinse outside of product bottle using small amount of H2O and transfer out of the hot cell
into a lead shield for radiochemical assay. Caution: 64Cu yields a 511 keV gamma due to
positron emission.
52
FIG. 2. Calculated production yields of copper-64 by neutron irradiation of enriched zinc-64 targets
as a function of irradiation time at various thermal neutron flux values.
FIG. 3. Calculated production yields of copper-64 by neutron irradiation of enriched zinc-67 targets
as a function of irradiation time at various thermal neutron flux values.
53
6. Transfer the lead shield to a radiochemical hood and prepare for radiochemical assay.
Make a dilution of 0.1 mL of product solution to 0.9 mL 0.1 M HCl. Prepare a counting
mount of 20 µl for assay on a J-Spectrometer. Assay is made using the 38.6% abundant
annihilation gamma (511 keV).
Solvent extraction processing of copper-67 produced after irradiation of enriched zinc-

67 targets (from ORNL nuclear medicine procedure # 45):
1. Dissolve 2.22 gm of thienyltrifluroacetone, TTA (M.W. = 222.18) in 50 mL of reagent

grade benzene (thiophene-free). The solution should be prepared fresh just prior to use.
2. For pre-equilibration, measure required volumes of organic and aqueous reagents into a
clean, dry separatory funnel. Contact phases for 5 minutes and allow phases to separate
for a minimum of 10 minutes. Drain aqueous phase into a clean, dry labeled stock bottle
and transfer organic phase through top of funnel into a separate clean, dry labeled stock
bottle.
3. Transfer Cu-67 target to "hot-cell" and remove from aluminum can. Crush ampule using
break-tube and vise. Pour contents into 150 mL beaker and rinse break-tube 2 times using
small aliquots of 1 N HCl (containing 5–10 drops of 30% H2O2). Transfer rinses to
150 mL beaker. Add 1 N HCl until volume equals 10.0 mL. Transfer beaker to hot-plate
and heat gently if necessary to dissolve ZnO.
4. After dissolution, transfer solution to a clean 150 mL beaker. Rinse beaker containing
quartz using small volumes of H2O, and transfer rinses to beaker containing Cu-67
solution. Evaporate solution to dryness, allow to cool, and add a small volume of H2O.
Evaporate slowly to dryness. Complete dryness on all surfaces is necessary at this stage
to ensure correct acid normality.
5. Allow residue to cool for 5 minutes, then dissolve solids in 15.0 mL 0.01 N HCl. Mix
well, and assay for Cu-67 (184.6 keV).
6. Transfer solution to a clean separatory funnel (labeled #1). Add 15.0 mL of pre-
equilibrated 0.2 M TTA and contact for 2 minutes. Allow phases to separate for
5 minutes.
7. Drain aqueous (lower) phase into a clean separatory funnel (labeled #2), and repeat above
step.
8. Drain aqueous (lower) phase into a clean bottle (labeled "holding bottle #1"). Set aside
bottle for ZnO recovery.
9. Combine organic phases into separatory funnel #2 and wash 4 times using 15.0 mL
volumes of 0.01 N HCl (pre-equilibrated using 0.2 M TTA/benzene). Drain the aqueous
phases from first and second washes into "holding bottle #1". Drain the third and fourth
washes into separate holding bottles (labeled accordingly). Monitor fourth wash if
possible, since detectable radioactivity should be very low.
10. Transfer organic phases through top of separatory funnel #2 into a clean separatory
funnel (labeled #3). DO NOT TRANSFER THROUGH STOPCOCK !!
54
11. Back extract Cu-67 from organic phases 2 times using 15.0 mL volumes of pre-
equilibrated 0.5 N HCl. Drain aqueous (lower) phases into a clean separatory funnel
(labeled #4). Drain organic phases into a separate holding bottle.
12. Wash aqueous phase in separatory funnel #4 using 15.0 mL volume of pre-equilibrated
benzene. Drain aqueous phase into clean 250 mL beaker and evaporate slowly under air
or argon stream. Air or argon stream decreases evaporation time. As evaporation volume
decreases, solution may appear yellow. This is a normal observation.
13. After evaporation is complete, fume several times using concentrated HNO3 to destroy
any remaining organic residue.*
*NOTE: If no solids are present, continue to Step #15.
14. Fume solids from step #11 using concentrated HCl to convert solids from nitrate to
chloride form. Add concentrated HCl 3 times and evaporate slowly under argon or air
stream.
15. Dissolve chloride solids in 10.0 mL. of 0.05 N HCl, mix well, and assay for Cu-67
(184.6 keV). After assay, store product in appropriate facility for future experimental use.
Zinc target recovery
1. Collect and combine “holding bottles” from Cu-67 processing that contain Zn-65, by
assay, into clean 150 mL beaker. Transfer beaker to hot-plate and begin evaporation
under argon stream. EXTREME care must be taken to avoid “burping” and splatter.
Loss of solution will decrease recovery yield.
2. During evaporation, assemble glass column using glass wool and Bio-Rad resin. Load
resin to a height of approximately 5" (12.7 cm). Pre-equilibrate column using 2.0 N HCl.
3. After evaporation is completed (all solutions containing Zn-65 are combined and
evaporated), allow ZnO solids to cool.
4. Dissolve solids in 20.0 ml of 2 N HCl and transfer solution onto pre-equilibrated Bio-Rad
column, and rinse beaker using small volumes of 2 N HCl. Transfer rinses to column.
5. Wash column using 100 mL of 2 N HCl and collect eluent in labeled glass bottle for
assay if necessary.
6. Wash column using 200 mL of 6 N HNO3, and collect solution in tared beaker #1.
NOTE: Monitor column and determine Zn-65 activity. If appreciable activity is present,
continue washing with 6 N HNO3, and collect eluent tared beaker #2. Save for additional
ZnO recovery.
7. Begin evaporation of Zn-65 solution under argon stream. During this evaporation, set up
furnace and test temperature using temperature controller. Furnace must be capable of
maintaining prescribed temperature setting.
55
FIG. 4. Apparatus use for the spontaneous electrodeposition of carrier-free copper-67 (from,
Mirzadeh, et al., 1992).
8. Continue evaporation until beaker is completely dry, and no condensate is present on

sides of beaker. When beaker is dry, transfer beaker containing ZnO solids to furnace and
start increasing temperature slowly. Observe temperature and maintain at 350oC for 2 h.
9. Remove beaker from furnace and cool to facility temperature. After beaker has cooled,
weigh tared beaker and calculate ZnO recovery yield.
10. Store recovered ZnO in appropriately labeled and shielded container.
Spontaneous electrochemical separation of carrier-free copper-65 and copper-67 from

zinc targets (from Mirzadeh, et al., 1992):
1. After irradiation, the Zn target (~50 mg) is dissolved in 2 mL of 6 M HCl containing

0.25 mL of conc. HNO3. The mixture is then evaporated to near dryness, and after
cooling, the residue is dissolved in 1 M H2SO4 yielding a solution ~10 mg/mL of Zn2+.
2. The electrolysis apparatus (Fig. 3) consists of a U-shape cell (three chamber right and left
half cells), a Zn electrode (1.5 mm O.D. rod) immersed in a saturated solution of ZnSO4 in
1 M H2SO4 (left half cell) and a Pt electrode (1.5 mm O.D.). The natZn(wire) target
material is of Puratronic grade and all metal electrodes should be of high chemical purity
(99.999%).
56
3. To eliminate traces of copper, the new Pt electrodes or electrolysis cells should always be
soaked in conc. HNO3 for several hours prior to use. A typical source of stable copper is
from the spotwelder contacts which are generally made from copper and leave traces of it
on the Pt.
4. The two electrolytes are separated by a porous barrier (10–20 micron fritted glass disc,
2 mm thick, ~2 cm2 surface area), which allows electrical contact but prevents excessive
mixing of the solutions by interdiffusion. The external connection of the two half cells is
simply achieved by connecting the Pt and Zn electrodes with a suitable conductor. During
the electrolysis, the right electrolyte is mixed magnetically, and the volume of each
electrolyte is 25 mL.
5. At the end of electrolysis, the Pt electrode is removed from the electrolysis apparatus, and
the deposited 67Cu dissolved by immersing the Pt electrode in concentrated HNO3 for 1–
2 minutes. The electrolysis is performed at room temperature, and the duration of
electrolysis is 30 minutes.
The final product should be analysed by gamma spectroscopy.
For the electrodeposition method, in a typical production run, the neutron-irradiated 67Zn
target (50–100 mg as ZnO) is dissolved directly in 25 mL of 1 M H2SO4 and transferred to the
electrolysis cell. After 30 minutes, when an assay of the right electrolyte indicates the
quantitative removal of 67Cu, the target solution is replaced with fresh 1 M H2SO4, and
deposition continued for an additional 30 minutes. This step is repeated once more and then
the deposited carrier-free 67Cu is dissolved by immersing the Pt electrode in concentrated
HNO3 for 1–2 minutes.
Although the routine production of copper-67 via the (n,p) reaction in a nuclear reactor is
probably not practical because of the relatively low yields and highly expensive enriched
zinc-67 target material, this route can be used as a back-up when accelerator-produced
copper-67 is unavailable.
BIBLIOGRAPHY
BROWN, L.C., CALLAHAN, A.P., “Copper-67 Processing and ZnO Recovery Procedure by
Solvent Extraction”, Nuclear Medicine Procedure # NMG-45, Life Sciences Division, Oak
Ridge National Laboratory, (L. C. Brown) 1972).
MIRZADEH, S., KNAPP, F.F., JR., “Spontaneous Electrochemical Separation of Carrier-free
Copper-64 and Copper-67 from Zinc Targets”, Radiochim. Acta, 57 (1992) 193–199.
MIRZADEH, S., MAUSNER, L., SRIVASTAVA, S.C., “Production of No-Carrier Adder
67
Cu”, Appl. Radiat. Isot. 37, (1986) 29–36.
RICE, D.E.,.Oak Ridge National Laboratory ‘Copper-64 Processing Procedure of Enriched
Copper-64 Target”, Nuclear Medicine Procedure # NMG-24, Life Sciences Division (1986).
57
Dysprosium-165 (165Dy66)
Half-life : 2.334 hours
Isomer half-life: 1.257 min (97.26% IT)

164
Production scheme : Dy (n,J) 165Dy V = 2650 ± 100 b
Decay energy : Beta decay (primarily)
E Emax = 1286.7 keV 83%

1192.0 keV 15%
J 94.7 keV
165
Decay product : Ho
Target specifications and preparation
MIT Research Reactor is used for irradiation because of its proximity to Boston’s hospitals.
The one inch pneumatic tubes (1PH1 and 1PH2, thermal neutron flux ~8 × 1012 n/cm2/s) are
normally used for the irradiation. Each sample contains 2 mg of natural dysprosium nitrate in
3% nitric acid and is irradiated for 6 hours.
The target solution was added to 1 mg of ferrous sulfate in 0.5 mL of 0.1 N hydrochloric acid,
and then 1 mL of 0.2 N sodium hydroxide was added to precipitate the ferric hydroxide
macroaggregate (FHMA). The 165Dy-FEMA was resuspended and washed twice with
polyvinyl pyrrolidone. The average particle size was determined to be 5 µm (range 3–10) by
serial filtration through nucleopore membranes.
The amount of 165Dy to treat patients with seropositive rheumatoid arthritis and persistent
synovitis of the knee is estimated to be 9.5–11 TBq (250–300 mCi) based on an extrapolation
from the clinical results of previous studies which found that 185 MBq (5 mCi) of 96Y-citrate
was adequate. 165Dy-FHMA was injected into the joint space after instillation of 1% lidocaine
hydrochloride in the skin and subcutaneous tissue.
BIBLIOGRAPHY
BARNES, C.L., et al., Radiation Synovectomy using Dysprosium-165 Ferric Hydroxide

Macroaggregates: A Review, Rheumatology Review (1992).

Li Wen,
Massachusetts Institute of Technology,
Cambridge, Massachusetts, United States of America.
58
HARLING, O.K., et al., Boron Neutron Capture Therapy and Radiation Synovectomy
Research at the Massachusetts Institute of Technology Research Reactor, Nuclear Science and
Engineering, 110 (1992) 330–348.
SLEDGE, C.B., et al., Treatment of Rheumatoid Synovitis of the Knee with Intraarticular
Injection of Dysprosium 165-Ferric Hydroxide Macroaggregates, Arthritis and Rheumatism,
Vol. 29 No. 2 (1986).
SLEDGE, C.B., et al., Synovectomy of the Rheumatoid Knee Using Intra-Articular Injection
of Dysprosium 165-Ferric Hydroxide Macroaggregates, Journal of Bone and Joint Surgery,
Vol. 69-A, No. 7 (1987).
59
Dysprosium-166 (166Dy66)
Half-life : 81.6 ± 0.01 h

164
Production scheme : Dy (n,J) 165Dy (n,J) 166Dy V = 2650 b
Target material : Enriched dysprosium-164
Decay energy : E (MeV) 0.404 (92%); 0.4327 (5%); 0.4869 (5%)

J (MeV) 0.08247 (13.8%)
166
Decay product : Ho
Dysprosium-166 is a lanthanide which can be reactor-produced by double neutron capture on

enriched dysprosium-164 (28.2% natural abundance) with relatively high specific activity
(Fig. 1) and decays to holmium-166, a beta-emitting radioisotope of interest for nuclear
medicine applications.
Enriched dysprosium-164 targets (>95%) as dysprosium oxide are irradiated.
Irradiation parameters, specific activity and total yield at end of irradiation
As shown in Fig. 1, even at low to moderate thermal neutron flux, multicurie levels of
dysprosium-166 can be produced by the radiative (n,J)(n,J) reaction.
FIG. 1. Projected reactor production of dysprosium-166 as a function of irradiation time for

various thermal neutron flux values.

S. Mirzadeh and F.F. Knapp, Jr.,
Nuclear Medicine Programme, Oak Ridge National Laboratory,
60
An adequately shielded hot cell is required for processing the irradiated target.
Processing of irradiated dysprosium-164-enriched Dy2O3 targets involves cooling the target

for the required time period, at ORNL 2–3 days, and then dissolution in 5–10 mL of 9 M HCl.
After evaporation to dryness, the residue is dissolved in 0.01 N HNO3 (Dadachova, et al.,
1994).
Solutions of the dysprosium nitrate can be dispensed as required. A modified dysprosium-

166/holmium-166 generator system (Dadachova, et al., 1994) has also been developed (200–
400 mesh AG 50WX × 12 resin) which provides carrier-free holmium-166 by elution with D-
hydroxyisobutyric acid (D-HIBA). Because of the very similar chromatographic properties of
dysprosium and holmium, however, following elution of holmium-166, the dysprosium-166 is
eluted also, requiring re-processing re-adsorption of the dysprosium-166 for each subsequent
run.
The radiochemical purity of the dysprosium-166 can be evaluated with a germanium crystal
detector system.
Processing of reactor-irradiated enriched dysprosium-166 targets is straight forward and

separation of carrier-free holmium-166 is feasible even on a high activity level.
BIBLIOGRAPHY
DADACHOVA, E., MIRZADEH, S., LAMBRECHT, R.M., HETHERINGTON, E.L.,

KNAPP, F.F., JR., “Separation of Carrier-free Holmium-166 from Neutron-Irradiated
Dysprosium Targets”, Anal. Chem., 66 (1994) 4272–4277.
61
Gadolinium-153 (153Gd64)
Half-life : 241.6.d
152
Production scheme : Gd(n,J)153Gd V = 735 ± 20 b
Type of decay and energy
EC (100%) J IC
0.06987 (2.42%) 11%
0.09743 (29.5%) 8%
0.1032 (21.1%) 30%
Target material : Spec pure Gd2O3 (JM Grade)
Target preparation
50 mg of the target is sealed in the standard aluminum can of dimension 22 mm dia × 46 mm

ht, which is cold-welded.
Irradiation period : 2 months

Neutron flux : 6 × 1013 n/cm2/s
Yield : 1.85 GBq (50 mCi)
Facility for processing
Standard glove box of dimensions 2 m × 1 m × 2 m fitted with 5 cm thick lead wall.
Chemical processing
The irradiated target is allowed to cool for about two weeks before taking up for chemical
processing to allow the decay of shorter half-life component, 159Gd (half-life-18.5 hours). The
irradiated can is cut open and the target is dissolved in 5 mL of 3N HCl. The solution is then
heated to enable complete dissolution of the powder and then diluted with 10 mL of 0.1N
HCl.
The radioactive concentration of the solution is determined by measuring the ion-current

produced by a known volume of the solution in a standardized ion chamber. The specific
activity is calculated knowing the quantity of the target irradiated and the final yield of the
product.
Characteristics of the solution
Chemical form GdCl3 in dilute HCl.

Radioactive concentration 37–185 MBq/g of Gd.
Specific activity >700 MBq/g of Gd.

M. Ananthakrishnan,
Department of Atomic Energy, Mumbai 400 085, India.
62
Gold-198 (198Au79)
Half-life : 2.69517 ± 0.00021 d

197
Production scheme : Au (n,J) 198Au V = 98.65 ± 0.09 b
Target material : Metallic gold with a purity of 99.9999%
E(MeV) 0.2847 (0.985%) J (MeV) 0.4118 (95.58%)

Emax 0.960 (98.99%) 0.676 (0.804%)
1372.4 (0.025%) 1.088 (0.159%)
198
Decay product : Hg.
Preparation of target Irradiation

for irradiation
Processing Calibration Quality Dispensing

in hot cell control
Target material: metallic gold in the form of wire, diameter 0.8 mm.
Reactor used: RA-3, 5 MW pool type research reactor. Thermal fluxes from 2 × 1013 to 1 ×
1014 n/cm2/s, 4 irradiation boxes with 14 places each one, and 120 hours of continuous
operation per week.
Capsule details: a quartz ampoule is used; dimensions are 40–50 mm long, 6–8 mm diameter.
The quartz ampoule sealed using an oxigen/gas blowpipe is placed with quartz wool into an
aluminium can (70 mm long, 20 mm diameter) wich is cold welded.
Mass of target per capsule: 100 mg of metallic gold.
Reactor irradiation parameters: flux 4 × 1013 n/cm2/s; irradiation time: 24 h
Specific activity achieved: 2.6 GBq (70 mCi)/mg.
Total activity under this conditions: 7 Ci EOI.
Impurity: 199Au <0.5%, other <0.5%.

Ezeiza Atomic Centre,
Comision Nacional de Energia Atomica,
Buenos Aires, Argentina.
63
The hot cell is a sealed box under reduced pressure (15–20 mm of water-reduced pressure),
with remote handling tong, and with a wall 5 cm of lead thickness as biological shielding.
Viewing windows are made of lead glass (10 cm thick). The windows are mounted in frames
fitting the interlocking lead brick system, and the space between the glass and the lead frame
is packed with lead yarn. The tong used has a detachable head to enable to change the types of
jaws without removing the tong from the box. A flexible plastic sleeve is attached to the tong
shaft to prevent contamination being carried into the laboratory when the tong is drawn
outwards. In addition there are a few special tools for opening cans and cutting quartz
ampoules, a rigid support for the glass material, a sealing machine for glass vials, a fume
hood and the glass vial containing the radioisotope solution (storage bottle).
For dispensing a remote operated pipette connected by means of a plastic tube to a

hypodermic syringe is used.
FIG. 1. Hot cell for the production of 198Au.
Reagents and chemicals required for processing
HCl (Hydrochloric acid, 0.1 N solution)

3 HCl-1 HNO3 (aqua regia)
H2O (bidistilled water).
After irradiation the aluminium can and the ampoule are opened in hot cell.
The irradiated gold wire is converted to gold chloride by reaction with aqua regia at 100ºC
and the excess of aqua regia is evaporated to dryness, in the case of seeds they are not
processed. The residual gold chloride is dissolved in 0.1 N HCl, assayed for radioactivity and
dispensed.
64
The final solution of 198AuCl3 (act.conc. 1.8–3.7 GBq (50- 100 mCi)/mL) is filtered through
Millipore filter 0.22 µm for dispensing or used for the production of gold colloides. For
quality control a 3 mL fraction is separated.
Radionuclidic purity: determined by J- spectrometry with a GeHp semiconducting detector

associated to a multichannel analyser.
Radiochemical purity: determined by paper chromatography.
Limpid, yellowish acid solution.

Radionuclide identification: 198Au.
Radionuclide purity: >99%.
pH of final solution: 1–2.
Radiochemical purity: >95%.
Concentration requirements: concentration activity at date of calibration: 1.8–3.7 GBq (50–
100 mCi)/mL.
Storage conditions: at room temperature.
65
Gold-199 (199Au79)
Half-life : 3.139 ± 0.007 d

198
Production reaction : Pt(n,J)199Pt (E-)< 199Au
199
Decay product : Hg (stable)
Target purity: Enriched 198Pt (95.31% 198Pt, <0.05% 190,192Pt, 1.06% 194Pt, 1.60% 195Pt, 2.03%
196
Pt and <0.05% 197Au) purchased from Oak Ridge National Laboratory (ORNL). Stable
gold in the target material shall be kept low to maximize specific activity.
Reactor : The V-14 thimble position at High Flux Beam

Reactor (HFBR) at Brookhaven National Laboratory
(BNL) (In = 4.2 × 1014 n/cm2/s) and the High Flux
Irradiation Reactor (HFIR) at ORNL (In= 1.58 × 1015
n /cm2/s).
Capsule details : 0.5 cm ID × 5 cm Suprasil (purchased from Heraeus)
quartz ampules.
Target mass : 5–20 mg of powdered metal.
Irradiation length : 3–5 days.
Specific activity, production yield:
BNL specific activity: ~ 7.5 GBq (205 mCi)/µg
ORNL Specific activity: ~ 7.5 GBq (205 mCi)/µg
Production Yield: >90% of theoretical
ORNL: (tb = 5 day) 12.2 GBq (330 mCi)/mg 198Pt
BNL: (tb = 4.02 day) 2.37 GBq (64 mCi)/mg 198Pt.
Processing shall be performed in a shielded hot cell with HEPA filtration in the hot cell
exhaust line.
All reagents used in processing were of analytical grade without further analysis.

L.F. Mausner,
Office of Isotope Production, Bldg. 801,
Medical Department, Brookhaven National Laboratory,
Upton, New York 11973, United States of America.
66
Reagents
Silica gel, SiO2 (100–200 mesh, DavisilTM) deactivated by treatment with dimethyl-
dichlorosiland (DMCS) as discussed in the reference given below; Tri-n-butyl phosphate
(TBP) was 99+% pure when purchased from Aldrich. All glassware was acid washed with
HNO3 before use. Nitric and hydrochloric acids were purchased from Aldrich. Nitric acid
solutions used on the columns was always presaturated with TBP prior to use.
Preparation
Columns were prepared by thoroughly mixing the hydrophobic silica gel with TBP until no
air bubbles remained on the support material. Columns were filled with the slurry and excess
TBP was eluted under pressure with presaturated 14 N HNO3. Under these conditions, the
absorption capacity was measured to be 0.18 g TBP per g of dried silica gel. The column was
then preconditioned with presaturated 1 N HNO3. Typical columns were 2.54–4 cm × 0.5 cm
ID.
Target dissolution
Enriched 198Pt targets were dissolved slowly (t ~ 1–2 h) in warm aqua regia.
Separation procedure
After dissolution, the solution was evaporated to near dryness and redissolved in 1–3 mL 1 N
HNO3. This solution was loaded on the column. Platinum was eluted with 30 mL of 1 N
HNO3 followed by 10 mL of 3.5 N HNO3 (typical flowrates were 1 mL/min). Gold-199 was
eluted with 10–15 mL of 14 N HNO3. This solution was gently evaporated to dryness using a
rotoevaporator. The residue was redissolved in aqua regia and converted to the chloride by
several evaporations to near dryness with HCl. The gold chloride was then redissolved in
methanol (2 mg/µL) for cluster synthesis.
Final products are assayed with regard to yield and radionuclidic purity.
Radioactivity measurements
Radioactive samples were assayed by direct J counting on an intrinsic germanium detector
(50 cm3, FWHM 2.0 keV at 1332 keV) connected to a 8192 multichannel analyser. The
detector was calibrated against a known mixed gamma solution standard traceable to NIST.
Counting samples were prepared in a plastic vial by dilution of the sample aliquot to 1 mL.
All samples were counted at distances >8 cm from the detector face where coincident
summing corrections are negligible.
Stable elemental analysis is made with spectrophotometric assay. From this data, the specific
activity may be estimated.
67
The final product was intended for use in radiopharmaceutical development by synthesizing
gold clusters and attaching them to antibodies.
Physical observations : The final product should be clear and colorless.
Radionuclide identification : by the 159 keV photon (37% abundant)
Radionuclide purity : Radionuclide impurity (due to 198Au) should total
<2% of 199Au activity
Solution pH : pH <1
Radiochemical purity : The radiochemical purity of is determined using
HPLC and spectrophotometric assay (for stable Pt).
Concentration requirements : Varies depending on application.
Shelf life and recommended storage conditions: Shelf life depends on specific activity
requirements of final preparation of antibody
conjugate. If not used immediately, the radionuclide
should be stored at pH <1.
Waste disposal : Waste disposal is similar for waste disposal of any
waste containing E/J radionuclides.
Preparation and cleanup considerations: Extraction columns are poured fresh for each
production run. Acid solutions are presaturated with
TBP immediately prior to each production run.
Silica gel must by hydrophobized before use to ensure consistently high 199Au recovery from
the target material.
BIBLIOGRAPHY
HAINFELD, J.F., FOLEY, C.J., SRIVASTAVA, S.C., MAUSNER, L.F., FENG, N.I.,
MEINKEN, G.E., STEPLEWSKI, Z., Radioactive Gold Cluster Immunoconjugates: Potential
Agents for Cancer Therapy, Nucl. Med. Biol. 17 (1990) 287.
199
KOLSKY, K. L., MAUSNER, L.F., Production of No-carrier-added Au for Gold Cluster-
labelled Antibodies, Appl. Radiat. Isot. 44 (1993) 553.
68
Gold-199 (199Au79)
(Alternate procedure)
Half-life : 3.139 ± 0.007 days
198
Production scheme : 78 Pt (n,J) o 199
78 Pt
p E-30 min
199
79 Au
199
Decay product : Hg
Reaction Isotopic Cross- Activity of element at

abundance section 1012 n/cm2/s
of nuclide% barn
One week Saturation
198
78 Pt (n,J) o 199
78 Pt
7.2 3.66 ± 650 MBq 1.19 MBq (22.26
0.19 (17.61 mCi)/g
p E-
199 mCi)/g
79 Au
E- 0.244 (21.5%) Gamma 0.1584 (40%) IC 36.4%

0.294 (72.0%) 0.2082 (8.72%) 9%
0.4526 (6.5%)
Target Spec.pure Pt sponge 100 mg. (J.M.).
Container Standard 1S aluminium can 22 mm dia and 44 mm ht. cold weld

sealed.
Irradiation 1.week
Flux 5 × 10 13 n/cm2/s.
Activity produced 3.7 GBq (100 mCi).
Type of facility for Standard glove box with 2 inch lead shielding.
processing

M. Ananthakrishnan,
69
Chemicals and reagents required for processing
HCl (AR Grade)

HNO3 (AR Grade)
Ethylacetate (AR Grade)
Processing
100 mg of irradiated platinum is dissolved in 10 mL aqua regia in a dissolution flask and

refluxed for 10 minutes. The solution is concentrated to approx. 0.5 mL and excess nitric acid
is removed by repeated treatment with 5 mL concentrated HCl each time. (This is done thrice)
Final solution is concentrated to approx. 0.5 mL and 25 mL 3 N HCl is added to it. The
solution is transferred to a 125 mL separating funnel. 25 mL ethyl acetate pre-equilibrated
with 3NHCl is added to the solution and gold 199 is extracted in ethyl acetate. (This
procedure is repeated thrice) Ethyl acetate fraction separated is washed with 3NHCl and
transferred to a distillation flask. Ethyl acetate is removed by distillation and the residue is
treated with 5 mL concentrated HNO3 to destroy any organic matter. Excess nitric acid is
destroyed by treatment with concentrated HCl. The solution is evaporated to near dryness and
activity leached out in 10 mL 0.1 N HCl.
Activity yield 100%.
Specific activity carrier free.
Activity determination J-measurement with ionization chamber. The radioactivity is

measured in a well type ionization chamber (ORNL).
Radionuclide purity is checked by J spectrometer using HP Ge detector.
Appearance A clear solution.
Chemical form HAU Cl 4 in 0.1 NHCl.
Specific activity Carrier free.
Radioactive concentration 370–740 MBq (10–20 mCi)/mL.
Radiochemical purity >99%.
70
Holmium-166 (166Ho67)
Half-life : 26.763 ± 0.004 h

165
Production scheme : Ho (n,J) 166Ho VnJ (g) = 61.2 ± 1.1 b
166
Decay product : Er68.
E energy: Max. 1853.9 keV (50%)

1773.3 keV (48.7%)
+ 4 others, low yield
Mean 0.67 MeV
J energy: 0.081 MeV (6.71%)

1.379 MeV (0.93%)
+ several others to 1.83 MeV.
Flow chart of the operation and procedures
Preparation of target o Irradiation o Cooling o Chemical Processing o Dispensing.

165
Target material : Ho(NO3)3. 5H2O or 165Ho2O3
Target purity
>99.9% Holmium(III) nitrate pentahydrate.
Enrichment factor, if applicable

165
Ho (natural abundance is 100%).
Impurity details (in irradiated sample)
Check radionuclidic impurities in an activated sample (typical results given below)

Instrument : GMS-25190 detector (EG & G, ORTEC)
Cooling time : 14 d

Kyung Bae Park,
Radioisotopes and Radiation Team, HANARO Centre,
KAERI, Taejon, Republic of Korea
71
Nuclide Half-life Activity (Bq) Initial Activity Remarks
Ho-166 26.8 h 573,200 3,3 E09 (92 mCi)
Ho-166m 1200 a 1,858 1,860 0.564 ppm
Lu-177m 160.9 d 1,550 1,646 0.5 ppm
Lu-177 6.71 d 8,390 35,621 10.79 ppm
Ce-141 32.5 d 457 616 0.19 ppm
Yb-169 32.02 d 2,488 3,369 1.02 ppm
Yb-175 324.19 d 17,640 178,695 54.15 ppm
La-140 40.22 h 90 29,412 8.91 ppm
Isotopic composition and supplier of target material and grade
Holmium(III) nitrate pentahydrate, >99.9% (Aldrich chemical company, Inc) or Holmium

Oxide.
1. Reactor used and which assembly (hydraulic tube, etc.) HANARO, HTS (Hydraulic
Transfer System) in D2O reflect region of HANARO
2. Capsule details (material, dimensions, encapsulation method, etc.) any special
precaustions for target encapsulation (degassing, low pressure, etc.)
– Sample container material: Titanium, Dia. 15 mm, length: 50 mm
– Inner capsule material: Aluminum 1050, Dia. 22 mm, length: 107 mm,
Sealing method: cold welding, 10–6 torr
– Outer capsule material: Aluminum 1050, Dia. 28 mm, length: 150 mm
Sealing method: tig welding in Helium chamber, 10–8 torr
3. Mass of target per capsle: 200 mg
4. Preparation of target for encapsulation, reactor irradiation parameters (flux, irradiation
time, etc.
– Thermal neutron flux in HANARO (at 20 MW, power): 4.2 × 1013 n/cm2/s
– Irradiation time: 60 h
– Cooling time: 30 h
5. Specific activity achieved and typical production yield per capsule
– Specific Activity: 2.28 GBq (75 mCi)/mg
– Production Yield per Capsule: approximately 90%
6. Any other pertinent information
1. Negative pressure: hot cell in: 9,000 zone, out: 8,000 zone, operation area: 7,000 zone
2. HEPA filter and activated charcoal filter
Analysis of raw materials, reagent and chemical required for processing
Holmium nitrate pentahydrate
Ho(NO3)3 5H2O, M.Wt, 441.02
It contains not less than 99.0 percent of Ho(NO3)3. 5H2O

1. Characteristics: A light yellow or orange, crystalline powder; odorless.
2. Identification
72
Weight out approximately 0.05 g and 0.1 g respectively and dissolve to 100 mL with 1%
nitric acid and complies with atomic spectrometry of Korea pharmacopoeia.
– Absorbency: 410.4 and 425.4 nm.
– Light source: Holmium lamp.
– Combustibles: mixed gas of nitrous oxide and acetylene (9:5).
3. pH: Between 4.0 to 6.0, in solution (1 in 100).
4. Moisture content: Between 20.4 to 22.2 percent.
5. Purity
5.1 Characteristics
Colourless or light orange in a solution (1 in 100).
5.2 Heavy metals
Dissolves 100 mg in 10 mL of 1% nitrate and complies with atomic spectrometry.
–Calcium: not more than 200 ppm.
–Erbium: not more than 30 ppm.
5.3 Arsenic
Weigh out 1 g and complies with limit tests for arsenic of Korea Pharmacopoeia
6. Assay
Approximately 100 mg is dissolved in 100 mL water.
Add 2–3 aliquot of xylene oragnge and titrate with 0.05 M EDTA until red colour
changed to yellow. Carry out the blank test.
0.05 M EDTA 1 mL = 22.051 mg Ho(NO3)3 5H2O
22.051 × B × f 100
Ho(NO3)3 5H2O (%) = ×
Wt 100 ( m 20.4)
Wt.: weight of sample (mg)

B: the amount of consumption of 0.05 M EDTA (mL)
f: Normality of 0.05 M EDTA
m: Moisture content (%).
1. Cask transfer from reactor to hot cell.

2. Operation with manipulator in hot cell: outer capsule o inner capsule cutting o titanium
capsule opening o target dissolved with HCl soln. (pH 3.0) o 0.2 µm Membrane filter
to 0 mL vial o dispensing in clean bench.
Dispensing, assay, quality control
Same for finished products.
Physical observation
A clear, light brown colour solution.
Radionuclide identification
The most prominent gamma rays of holmium-166 have energies of 80.6, 1379.4 keV.
73
Record the gamma ray and X ray spectrum using a multi channel analyser The spectrum does
not differ significantly from that of a standardized solution of holmium-166.
PH of final solution
Between 2.0 to 4.0
Examine by thin-layer chromatography using silicic acid as the coating substance on a instant
thin layer sheet. Apply to the plat 5 µl of the solution to be examined. Develop immedicately
over a path of 10 cm using a solution (methanol: water: glacial acetae = 100: 100: 1) Allow
the plate to dry in a current of cold air. Determine the distribution of radioactivity using a
TLC scanner. Holmium-166 nitrate migrates with an Rf value of 1.0. Not less than 95% of
total radioactivity of the chromatogram corresponds to holmium-166 nitrate.
Concentration requirement for specific application specific volume
The specific radioactivity is not less than 2.28 GBq (75 mCi0 of holmium-166 per milligram
of holmium.
Half-life and recommended storage conditions
Half-life is 26.7 hour. Holmium nitrate [166Ho] sterile solution should be used not later than 3
days from the date stated on the label.
Special comments on disposal of waste generated
None.
Preparation and cleanup of the facility and preparation for processing of next batch
Complies with GMP.
74
Iodine-125 (125I53)
Half-life : 59.408 d
Production scheme
E, 18 h
124
Xe(n,J)125Xe 125
I V = 165 ± 20 b
125
Decay product : Te
Iodine-125 decays directly to the excited state at 0.03549 MeV by electron capture. Only
6.68% of this excited state decays to the ground state, to 125Te stable nuclide. The remainder
93.32% decays by internal conversion. As a consequence of electron vacancies in inner shell
results in characteristic X ray, the main energy is 0.028 MeV.
EC: 100% Gamma: 0.03549 MeV, (6.68%)
X ray: 0.028 MeV
Cross-section data for 124Xe(n,J)125I reaction are, as follows:
Vm = 28 b, Vg = 137 b
As natural xenon target contains 124Xe nuclide in 0.096% only, there are two options to
produce high yields of 125I: (i) long irradiation of natural xenon, (ii) use of enriched xenon
target. In the former case it is necessary to calculate with the following nuclear reaction:
125
I(n,J)126I
since the forming 125I radionuclides can also capture neutrons with a cross-section of 900 barn
which leads to the presence of 126I radionuclidic impurity. If long irradiation of the natural
xenon target is performed the amount of the 126I impurity can be decreased by cooling since
the physical half-life of 126I is shorter (13 days). If the construction of a loop in the nuclear
reactor is possible, the circulation of the natural xenon target can ensure extremely low level
of 126I since the forming 125I radionuclides are immediately taken away from the circulation.
In case of using enriched xenon-124 target, the short irradiation period keeps the 126I content
on low level. On the other hand the recovery of the expensive enriched xenon target is
required.

J. Környei,
Institute of Isotopes Co., Ltd.,
H-1535 Budapest, P.O. Box 851, Hungary.
75
The flow chart of the technology is given below:
nat
Xe, target (124Xe target, enrichment >99%)
irradiation in nuclear research reactor
125
Xe
cooling for E- decay to obtain 125I
125
I
opening capsule, (target recovery in case of enriched xenon)
dry distillation of 125I from the inner wall of aluminium container,
absorption in alkaline medium e.g. 0.05 M NaOH
125
I-sodium iodide bulk solution
dispensing,
131
I-sodium iodide solution for labelling various compounds.
Target specification
Target purity
Xenon gas, 99.99%.
Enrichment factor
Natural isotopic composition, 124Xe content: 0.096%.

(Enriched xenon-124, enrichment factor >99%).
Impurity details
No detectable impurities.
natural xenon enriched xenon-124

124
Xe: 0.096% >99%
126
Xe: 0.09% 0.05%
128
Xe: 1.92% 0.01%
130
Xe: 4.80% 0.01%
132
Xe: 26.9 % 0.01%
134
Xe: 10.4 % -
136
Xe: 8.87% -
Supplier of target: Campro Scientific BV., 3900 AH Veenendaal, The Netherlands.
Irradiation parameters, specific activity and total yield at the EOI
Reactor
Nuclear research reactors with a neutron flux of 1 × 1013 – 1 × 1014 n/cm2/s can be used.
Higher fluxes should be avoided as the pressure in the target capsule containing natural xenon
can inrease up to 50 kg/cm2 during irradiation. Water cooling of the target within the
irradiation channel, during the whole irradiation, is necessary.
76
Capsule details
Irradiation capsule is made of aluminium containing magnesium in 0.3–1.5%, silicium in 0.2–

1.5%, manganese up to 1.5%, iron in 0.5%. This composition ensures the firmness of the
capsule against the pressure of the target gas. Dimensions of the irradiation capsule are:
diameter 27mm, height 200 mm.
Mass of target per capsule
The capsule contains 15 g of natural xenon or 0.4 g enriched xenon-124.
Preparation of target for encapsulation and irradiation parameters
15 g of natural Xe gas is filled into the aluminium capsule in the filling equipment showed in
the Fig. 1. The aluminium capsule is fixed to the tube and liquid nitrogen containing Dewar
bottle is placed under the Al-capsule. The capsule is immersed into the liquid nitrogen. The
valve is opened and pressure is adjusted to 6 bar. Vacuum pump is connected to the tube end
and it is switched on and operated for approx. 3 minutes. The aluminium capsule is vacuumed
followed by filling it with xenon gas up to a pressure of 5 bar three times as 5 bar pressure
corresponds to 5 g natural xenon gas. Finally the aluminium capsule is removed (asbest
gloves!) and plugged with hand pressing machine. The aluminium capsule is left to warm up
to room temperature and the leak-tightness is tested in glicerine at a temperature of 120–
240oC.
FIG. 1. Scheme of xenon filling.
In case of enriched xenon-124 capsule filling is performed by similar way with the exception
of the pressure adjusted since only 0.4 g of target should be encapsulated.
Fluxes up to 1 × 1014 n/cm2/s can be used, a typical flux used is 5 × 1013 n/cm2/s. At least
200 hours irradiation is requiered which can be extended up to 300 hours from point of view
77
of higher yields. After irradiation a cooling period of at least 120 hours is required to
complete E decay for obtaining iodine-125. In addition to this further cooling for 30–40 days
is necessary so that the 126I content should decrease to an acceptable level.
In case of the use of enriched xenon-124 irradiation for 10–24 hours is sufficient followed by
a 10–20 days cooling period.
SPECIFIC ACTIVITY ACHIEVED AND TYPICAL PRODUCTION YIELDS/CAPSULE
Flux, n/cm2/s 5 × 1013

Target natural Xe enriched 124Xe
Mass of target, g 15 0.4
Irradiation time, hours 200 300 10 24
Cooling period, days 40 45 20 20
125
Yield of I, 29.15 40.32 50.71 121.2
GBq
126
I content, 0.77 0.89 0.02 0.11
after cooling,%
Specific activity, Theoretical specific activity of the carrier-free iodine-125 = 646.02
GBq/mg Obtained: >600
For iodine-125 production two hot cells under negative pressure with 2–2 manipulators, as
well as air ventilation system with iodine (aerosol) filter is required. Hot cells are made of
iron with a lead shielding of 15 cm. The window of the hot cell is made of lead glass with a
thickness of 20 cm. One hot cell is prepared for the target opening and for the distillation
equipment, the other is used for dilution, dispensing and sterilization of the 125I-sodium iodide
solutions. Any other conditions (e.g. radiation protection system, etc.) should correspond to
the regulations being valid for isotope laboratories of level "A".
In case of the use of enriched 124Xe as target, the recovery of the irradiated xenon in a hot cell
is necessary.
1. Natural xenon gas or enriched 124Xe gas target, see the specifications above. No other
analysis than trial irradiation and the determination of the radionuclidic purity as well as
radiochemical and chemical purity of the 125I obtained are suggested.
2. Sodium hydroxide
Sodium hydroxide white pellets, grade extra pure is used (DAB, Ph.Eur, BP).
Identification is performed by flame photometry. Drops coming from the aqueous
solution of NaOH give a bright yellow colour. Content determination is carried out by
acidi-alkalimetric titration.
The aluminium capsule is opened in the first hot cell. When the needle punches the
aluminium the Xe gas is released into the chimney and the 125I radioisotope is adsorbed on the
inside wall of the aluminium capsule.
78
Before placing the capsule into the dry distillation equipment two holes with diameter of
approximately 5 mm is advisable to drill through the wall of the alumium capsule at the lower
one third part to increase efficiency of the distillation. The dry distillation equipment can be
shown on Fig. 2. It consists of a furnace (1), a quartz bridge (2), an acidic washing vessel (3)
and alkaline collectors (4a,b). The distillation is followed through 120 minutes at a
temperature of 550oC.
FIG. 2. Dry distillation equipment.
Dispensing and quality control
Dispensing
The 125I-NaI solution is transferred to the second hot cell. Radioactive concentration of the
fractions is determined. Based on the measured radioactive concentration the required value
should be adjusted dilution with 0.04 M NaOH. Solutions of the required radioactive
concentration are dispensed to portions into vials. If sterile product is required ampoules
should be autoclaved for 30 minutes at a temperature of 120oC.
Determination of radionuclidic purity
A vial containing 5–10 MBq I-125 sample is measured. Main gamma-peak of 125I are: 28 keV
(X ray) and 35.49 keV (J-ray). Impurity limit: not more than 0,9% of 126I (gamma of 380 keV
and 650 keV, beta: 390 keV, 870 keV and 1250 keV, positron: 460 keV and 1110 keV). A
gamma spectrum of iodine-125 can be seen in Fig. 3.
79
FIG.3. Gamma spectrum of 125I.
Determination of radiochemical purity
Paper electrophoresis is used. Paper stripes, type Whatman No.3 MM for electrophoresis,
possess dimension of 65 × 3 cm. Dropping of 10–20 µl samples takes place in a distance of
10- 13 cm from the end of the stripes. Borate buffer is used, concentration 9 g/l, pH=9 +/–0.1.
Electrophoresis is carried out on a potential of 900 V. Time: 50 min.
Rf values: product, i.e. iodide Rf = 0.7–0.9
impurities: iodate: Rf = 0.4
periodate: Rf = 0–0.1
elemental iod: Rf = 0.
Product can be accepted if the I-125-iodide anion content is higher than 95% even on the
expiration date.
1. Physical observation: Clear, colourless solution.

2. Radionuclide identification:
Iodine-125 radionuclide is identified by gamma spectrum (see above characterization).
3. Radionuclidic purity: should be higher than, or equal to 99.1%, i.e. 126I content should be
less than 0.9%.
4. pH of final solution: 8–10.
5. Radiochemical purity:
Measured by the above detailed electrophoresis, it should be higher than 95%.
6. Concentration requirements:
a) Product of high radioactive concentration
>7400 MBq/mL, chemical content: 0.04 M NaOH, reductant-free
b) Product of medium radioactive concentration
1850–7400 MBq/mL, chemical content: 0.04 M NaOH, reductant-free
c) Product of low radioactive concentration.
<1850 MBq/mL, chemical content: 0.04 M NaOH, reductant-free.
80
7. Shelf life and recommended storage conditions.
Expiry: production + 60 days, storage at room temperature.
8. Special comments of waste generated:
Wastes should be collected and left for decay. No special prescriptions are given, the
normal radioactive waste tretament procedures described for isotope laboratories should
be applied. Do not let iodine-125 to be contacted with acidic medium!
9. Preparation and clean up of the facility for next production.
The distillation equipment is surely contaminated and should be dismounted by
manipulators in the hot cell. Acidic and alkaline solutions should be taken off into
separate vessels. The quartz bridge should be washed in 1 M NaOH and finally rinsed
with water.
Iodine-125 production from natural xenon gas target is a safe method if irradiation capsules
made of aluminium are well prepared and well-controlled against both negative and positive
pressure in order to avoid the xenon loss as well as the explosion of the capsule during
irradiation. This method has been used in Hungary for more than 20 years without any
breakdown. The air coming from the hot cells of 125I production should be filtered by using a
multilayer filter which is capable of capturing radioactive aerosols as well.
In case of the use of enriched xenon the proper closing of the aluminium capsule is the crucial
factor for avoiding the eventual loss of the very expensive target. A careful servicing of the
equipment can help.
BIBLIOGRAPHY
DEWANJEE, M.K., RAO, S.A., “Principles of radioiodination and iodine labelled tracers”,
Radiotracers for Medical Application, CRC Press, Vol. II, Boca Raton (1983).
FIRESTONE, R.B., Table of Isotopes, CD ROM Edition, (SHIRLEY V.S., CHU S.Y., Eds.)
Version 1.0, Office of High Energy and Nuclear Physics, US Department of Energy (1996).
MYERS, G.W., Radioisotopes of iodine, (Proc. Symp. Oak Ridge, 1965), USAEC Techn.
Information Extension, Oak Ridge (1966) 217.
MYERS, W.G., VANDERLEEDEN, J.C., Radioiodine-125., J. Nucl. Med. 1 (1960), 149; 16
(1971) 565.
81
Iodine-131 (131I53)
(Wet distillation method)
Half-life : 8.04 days

Production scheme:
E E
130 131 131 131
52 Te (n, J) Te o
52 53 I o 54 Xe
Target material : Tellurium metal powder
131
Decay product : Xe
Reaction Abundance Cross- Activity of element at Side reactions and half-life of
of target section 1013 n/cm2/s nuclide formed.
nuclide barns 24 h. 7 Satu-
% days ration
120
130
Te(n,J) 131mTe 33.8 0.04 14.8 292 650 Te(n,J) 121gTe
E–7.8% MBq MBq MBq Half-life: 17 days
30 h. (1.4 (7.9 (17.5 Isotopic abundance: 0.089%
mCi) mCi) mCi) V = 2.0 barn
131 /g /g /g
IT 22.2% I
E-
25.0
min 120
Te(n, J) 121mTe
33.8 0.2 Half-life: 154 days
V = 0.34 barn
130
Te(n,J) 131gTe 30 h
250 1.4 3 GBq 122
Te(n,J) 123mTe
MBq GBq (83.0 Half-life: 119.7 days
(6.8 (38.0 mCi) Isotope abundance: 2.46%
mCi) mCi) /g V = 1.1 barn
/g /g
124
Te(n,J) 125mTe
Half-life: 47.4 d
Isotopic Abundance: 4.61%
V = 0.04 barn
126
Te(n,J) 127g Te
Half-life: 9.4 hours
V = 0.9 barn
126
Te(n,J) 127mTe
Half-life: 109 days
V = 0.135 barn
128
Te(n,J) 129 Te
Half-life: 69.6 minutes
V = 0.14 barn
128
Te(n,J) 129mTe
Half-life: 33.6 days
V = 0.015 barn

M. Ananthakrishnan,
82
E- 0.25 2.1% approx. Gamma 0.08 2.6%

0.33 7.27% 0.177 0.26%
0.304 0.651% 0.284 6.14%
0.608 89.9% 0.325 0.274%
0.81 0.48% 0.364 81.7%
0.503 0.36%
0.636 7.2%
0.722 1.8%
0.164 0.6%
Via 11.8 d
131
Xem
Targe specifications : Heavy metals like Ag, Au, Pb <0.005%
Anions like Cl, SO4 <0.01%
Irradiation parameters
Reactor used Dhruva reactor in BARC complex, Mumbai, India.
Capsule details 1S Aluminium can 22 mm dia × 44 mm ht.
Target material Natural Tellurium

20 g.in one can-cold weld sealed
(3 × 20 g. in one batch).
Irradiation time and 3 weeks at a flux of 1014 n/cm2 /s.

flux
Typical production 9.25–11.1 GBq (250–300 mCi)/g of Te at EOI.
yield
The radiochemical processing of I-131 is carried out in sealed boxes (Al or SS) kept under
negative pressure (2–3 cm WG) and provided with 4 inch lead shielding. The boxes are
connected to iodine filters (charcoal) fixed at the top.
Raw materials, reagents and chemicals required for processing
All the reagents used is chromic acid, sulphuric acid, oxalic acid, sodium sulphate, sodium
hydroride are AR/GR.
The irradiated can containing 60g tellurium powder is opened and the contents are transferred
into a 4-necked 5 lit distillation flask. The oxidation mixture consisting of 360 mL of 15 N
chromic acid solution and 960 mL of 50% H2SO4 is loaded into the dissolution flask. The
mixture is then refluxed for two and half hours using infra red lamps to heat the flask. After
dissolution, the mixture is cooled for 3 hours by passing water through a cooling coil fitted to
the centre neck of the flask. 240 g of oxalic acid dihydrate are added to reduce the excess of
83
chromic acid. After about half-an-hour of completion of reduction reaction, the flask is heated
using the infra red lamp. The receiver flask is cleaned with double distilled water and ten
millilitres of 0.01 N Na2SO3 is transferred to it. The distillation of iodine-131 is carried out for
half an hour or till no more iodine-131 distils into the receiver flask as indicated by the
reading in the ion chambers kept close to the dissolution flask. The flask is allowed to cool for
15 minutes. The pH of distillate is adjusted to approx. 8 by adding necessary quantity of 1 N
NaOH solution. The contents of the receiver flask is concentrated to a small volume to obtain
the necessary radioactive concentration of 250–400 mCi/mL. Finally the radioactive iodine-
131 solution is transferred into a storage bottle (Fig.1).
FIG. 1. Iodine-131 production facility.
The activity is assayed by taking the ion current measurement of known volume of stock
solution in a calibrated ion chamber.
Radionuclide identification is performed by checking the 0.36 MeV (81.2%) gamma peak.
The gamma ray spectrum is examined for any other gamma emitting impurities.
This is determined by a paper chromatogram, using iodide and iodate carrier and a solvent
mixture of 75% methnol and 25% water adjusted to pH 7–8 with potassium carbonate.
Rf value of I- = 0.75
Rf value of IO3- = 0.50
Rf value of IO4- = 0.00
The iodide content must be more than 95% in a typical batch. The total solid content is
determied by evaporating a known volume of the stock solution and weighing the residue.
Any heavy metal impurity is estimated colarimetrically.
84
Total reducing agents: A known amount of stock solution is treated with a known excess of
potassium permanganate solution and the excess of permanganate is back litrated against
standard oxalic acid solution. The reducing agent content is expressed in millilitres of 0.1N
KMnO4 per mL of Na 131I solution.
Characteristics of the final solution
Code I-2 (Non-injectable)

Iodine-131 as Na 131I in dilute alkaline
sulphate solution.
Radioactive concentration 7.4–14.8 GBq (200–400 mCi)/mL
Na 131I product specification
1 Description A clear colourless solution.On standing, glass and solution

may darken.
2 Radionuclide By photopeak corresponding to the principal of gamma
identification peak 0.36 MeV.
3 Radionuclide No other extraneous gamma emitting radionuclide is
purity detectable in the gamma ray spectrum.
4 PH 8–10.
5 Radiochemical The activity in the Na 131 I zone shall not be less than 95%
purity of the total activity.
6 Sodium sulphite l 10 mg/ 3.7 GBq (100 mCi) of 131I.
content
7 Assay for activity In mCi/mL
8 Tellurium content <5 µg/mL.
9 Storage In glass vials .
Chemical reaction
The following reactions take place during the oxidation of tellurium and subsequent reduction
with oxalic acid prior to the distillation of iodine:
1. Te + 2H2CrO4 + 3 H2SO4 o Cr2 (SO4)3 + H2Te04 + 4H2O
3I2 + 10 H2CrO4 + 15 H2SO4 o 5 Cr2(SO4)3 + 6HIO3 + 22 H2O
2. H2TeO4 + H2C2O4 o H2TeO3 + 2CO2n + H2O.
2HIO3 + 5 H2C2O4 o I2 + 10CO2n + 6H2O.
The distilled iodine reacts with the sodium sulphite and sodium hydroxide solution in the
receiver flask.
3. I2 + Na2 SO3 + H2O o Na2SO4 + 2H I
2H I + 2 NaOH o 2 NaI + 2H20.
The following observations merit attention:

– Distillation of iodine from the acid solution of Te containing gold in excess of 200 ppm is
observed to be incomplete.
– If tellurium metal of fine particle size (>100 mesh) is used for irradiation, it leads to
irdent reacton, at times leading to exlosion, during the dissolution stage.
85
Iodine-131 (131I53)
(Dry distillation method)
Production scheme
Iodine-131 is produced by the neutron irradiation of tellurium according to the nuclear

E
reaction 130Te(n, J) 131Te o 131I. The iodine is separated from the target material by dry
distillation above 750oC and absorbed in dilute sodium hydroxide solution.
Production process
The 131I production process: 131I is produced by the irradiation of TeO2 in the heavy water
research reactor. After irradiation, the 131I is dry-distilled off and absorbed in an alkaline
solution containing sulfite, dispensed according to the pharmacopoeia. The overall yield of
131
I is 952%. The whole process is described in Fig.1.
Powder TeO2
p
Dry at 200oC
p
Pill at 8 Mpa
p
Sinter at 650oC
p
Seal in Target Capsule
p
Target Irradiation
p
Dry-distillation and absorption
In dilute NaOH solution
p
Dispensing
p
p
Distribution
131
FIG.1. I production process.
1. Target purity: TeO2>99.9%(A.R)

2. Impurity details:

Jin Xiao Lai,
Department of Isotope, CIAE,
Beijing, China.
86
I No 127I Tl: <0.001%
Al <0.001% Mg: <0.0003%
Na <0.03% Ca: <0.001%
Sr <0.003 Sn: <0.0003%
P <0.00001% Cu: <0.0003%
Fe <0.01% Mn: <0.0003%
As <0.000001% Ba: <0.01%
Cd <0.001% Si: <0.1ppm
3. Isotopic composition and supplier of target material and grade isotopic composition:
Te 120 122 124 125 126 128 130

% 0.096 2.60 4.816 7.14 18.95 31.69 33.80
Supplier of target material: Beijing Chemical Factory (A.R.)
1. Reactor: heavy water research reactor.

2. Target capsule: Double-layer Aluminum cans sealed by cold-welding. Internal
dimension: 39mm-diam+ 68mm high.
3. Mass of target per capsule: 80g TeO2 .
4. Reactor irradiation parameters
Flux: 1.1+1014 n/cm2/s
Irradiation time: 6 days.
5. Specific activity achieved: above 740GBq(20 Ci)/mg iodine
Yield per capsule: 481GBq (13 Ci).
The facilities for dry-distillation of 131I showed in Fig. 2 are placed in a hot cell with an
exhaust line.
Hot cell wall-thickness: 20cm cast steel and 10cm lead.
Hot cell dimension: 1550L+1200W+2600mmH.
Negative pressure: Maintain at the negative pressure of 20mm H2O.
The exhaust line: The radioactive waste gas should pass through the 2.0mol/L NaOH,
0.5mol/L Na2SO3 solution, the activated charcoal filter and then get into the radioactive
management factory.
FIG.2. 131I separation apparatus.
87
No chemical purity determination is made, except a periodic check of TeO2 by emission

spectroscopy. Other reagents: analytical grade reagent.
1. The powder TeO2 heated at 200oC for two hours.

2. Make the powder TeO2 sintered into a pill under the pressure of 8MPa by press.
3. Put the TeO2 pill into an oven and heat it at 700oC for half-hour.
4. Put the TeO2 pills into double-layer can and seal it by cold-welding, leak check up to
standard.
5. Put the target can into the reactor.
6. Irradiate the target at the flux of 1.1 × 1014n/cm2/s for 6 days.
7. Cut off the aluminum can by a cutting apparatus in the hot cell.
8. Heat the irradiated TeO2 at above 700oC for 1.5 hours, and dry distillation the 131I. A
slow flow of carrier gas (2–3bubbles/s) is passed into the dry distillation apparatus. The
131
I is absorbed in the 0.01mol/L NaOH solution.
Sample 131I solution in an ampoule vial and samples are assayed for 131I concentration, pH
value, radionuclidic purity and radiochemical purity.
Dispensing
The 131I is separated from the target TeO2 by dry distillation and absorbed in 17 mL of a
mixed solution of 0.02M NaOH-0.004M Na2SO3. Then the solution is adjusted to pH7–9 with
distilled water i.e. final product.
Radioactive concentration is determined by a CAPINTEC CRC-30 BC ionization chamber
with 226Ra standardized source. The 226Ra source has been previously compared with the 131I
source calibrated by absolute measurement.
Gamma-emitting impurities in the solution are determined by gamma spectrum, using a high
purity Ge(Li)-detector and a multi-channel pulse height analyser.
By ascending paper chromatography using the methanol: water (4:1) solvent developing
system.
Chemical purity
Tellurium content is determined by double-channel Hydride-Generation atomic fluorescence
spectrometer.
1. Physical observations: colorless clear solution. No suspended particles presented.

2. Radionuclide identification: Its gamma ray spectrum is identical to that of specimen of
iodine 131 of know purity that exhibits a major photopeak having energy of 0.364 MeV.
The gamma spectrum of 131I product is shown in Fig. 3.
3. Radionuclidic impurity: 0.01%~0.0001%.
88
4. pH: 7~9.
5. Radiochemical purity: >95%.
The method of determination is paper chromatographs of the usual way.
6. Radioactive concentration and application
1.85–3.7 GBq/mL for diagnosis and/or therapy thyroid disease.
73.7GB1/mL for radioisotope labeling.
7. Shelf-life and recommended storage condition
Expiry: The expiration of 8 days after reference date is indicated on the quality certificate
and on the labels.
Storage: In lead container at room temperature.
8. Preparation and cleanup of the facility and preparation for processing of next production
batch.
(a) Put the dry-distillated target material into a special steel can for storage.
(b) Wash the hot cell floor to clean up all the powder TeO2 and liquid waste that may be
thrown off during the processing.
Keep all the transportation system, the heating system and the adsorbing system in a good
state for production of next batch.
FIG. 3. The gamma spectrum of 131I product.
89
Iodine-131 (131I53)
Iodine-131 is produced from the irradiated tellurium dioxide in a neutron flux, while
contained in a welded aluminum capsule, according to the nuclear reaction as follows
The irradiated tellurium dioxide powder is transferred to a Vycor distillation vessel and
connected to the iodine-131 tellurium processing system. The processing furnace is heated to
750oC in order to distill the iodine-131 over to a charcoal column trap connected in-line of the
distillation system. The charcoal column trap is rinsed with the de-ionized water then eluted
with sodium hydroxide 0.05N to form the final product iodine-131 solution. The scheme
below shows the flow chart of the operation and procedures.

The target used in the production is an analytical grade material of natural tellurium as
tellurium dioxide obtained from Fluka Inc. The chemical purity of the target as TeO2 is >95%.
The specification of the target before being fired in a muffle furnace through analysis by
emission spectrograph should contain of selenium less than 0.05% and heavy metals less than
0.1%. After being fire in the muffle furnace the analysis should give selenium less than
0.005% and heavy metal less than 0.1%.
Irradiation is performed at a nominal thermal neutron flux of 1.0 × 1014 n/cm2/s for 120 hours
at reactor core of CIP (Central Irradiation Position) in MPR-30 (Multi-Purpose Reactor 30
MW). Irradiation capsules are made of aluminum, type A1050, and comprised as an inner
capsule and an outer capsule. The dimension of the inner capsule is 200 mm (length), 24.4
mm (diameter), and 1.5 mm (thickness), whereas that of the outer capsule is 457 mm (length),
30 mm (diameter), and 2.3 mm (thickness).
Encapsulation method of the inner capsule is performed by welding aluminum plugs onto
both ends of the capsule tubing, whereas that of the outer capsule is carried out by welding an
aluminum plug onto one end of the tubing and screwing a cap on the other end. The integrity
of the weld of the capsules is inspected. Once the construction of the capsule is complete the
capsule is cleaned in ultrasonic bath for 30 minutes using trichloroethylene, then dried in oven
at 110oC for at least one hour.

A. Hanafiah Ws.,
Radioisotope Production Center,
National Atomic Energy Agency,
Indonesia.
90
Mass of target per capsule is 100 g of tellurium dioxide. Target preparation is carried out as
follows. The target material is transferred to porcelain crucible and placed in a muffle furnace
at temperature 500oC for 2 hours. The tellurium dioxide is allowed to cool to room
temperature and placed in a ball mill and broken up until it has a fine texture. The precise
quantity of target material is carefully transferred to the clean dried inner capsule and an
aluminum plug is placed in the open end and welded closed. The leak of the capsule is
checked by immersing the capsule in water and bubble checking in a vacuum of at least 30%
of Hg and stored until it is transferred into the outer capsule scheduled for irradiation in the
reactor core. If the target capsule is not used for a period of time the leak test is repeated prior
insertion into the reactor core.
The activity of I-131 at the end of irradiation (EOI) by irradiating 100 g TeO2 at a thermal
neutron flux of 1.0 × 1014 n/cm2/s in reactor for 120 hours is 740 GBq (20 Ci), so the total
yield at EOI is ~ 83.3%.
The facilities for processing include glove box, hot cell, and supporting areas, which equipped
with the ventilation system, such as carbon filter, pre-filter, HEPA filter, etc., for nuclear
grade installation. A glove box is used for dispensing low activity final product.
The hot cell include master slave manipulators, shield window, a conveyor for
interconnecting with other hot cells, an overhead shield plug (to allow for the removal of hot
cell containment box and equipment), and a shield door on the back side. The cell was lined
or coated with material that facilitates decontamination, and containment box is provided to
minimize the spread of contamination.
Concrete shielding walls of the cell consists of higher-density hematite concrete (minimum
density 3.0 g/cm3. Glove box and fume hood filter housings were shielded with 1.3 cm of lead
as required. Other local shielding are used as necessary to reduce dose rates.
Ventilation exhaust from radioactively contaminated areas and areas in which radioactive
materials are handled (except materials packaged for shipping) will flow through HEPA
filters to protect against inadvertent release of radioactive materials. Ventilation exhaust from
the hot cell will also flow through charcoal filter for absorption of any gaseous iodine prior to
release. If there is a loss a normal power, emergency electrical power will be provided to
maintain at least 50% of the ventilation exhaust flow rate from general areas that are
potentially contaminated. In addition, hot cell ventilation exhaust will be operated at a
sufficient flow rate to maintain negative pressure in the cell with all doors and inlet dumpers
closed. The ventilation exhaust systems were designed to achieve internal negative pressure
up to 76 mm of water for hot cell and up to 51 mm of water for glove box, respectively.
Analysis of raw materials, reagent and chemicals required for processing is performed to
confirm that all materials comply to the specified criteria for processing. Analysis includes the
determination of chemical purity and concentration by emission spectrograph and titrimetric.
The acceptable impurities of tellurium dioxide raw materials through analysis by emission
spectrograph should show selenium content less than 0.05% and heavy metal content less than
0.1%.
91
The target capsule is transported from the reactor using the transfer cask to the hot cell for
processing after the irradiation process is complete. The processing reagents and supporting
components required to process the target material are transported to the hot cell using the
inter-cell cart system.
The flow chart of iodine-131 processing is shown in Fig. 1 and the processing is carried out as
follows:
3. Check the engraved serial number on the target capsule and confirm to the correct target
capsule for processing, and then the capsule is stood on end.
4. Completely vibrate the target capsule using a vibrating tool to knock down any target
material which might be on the side walls of the target capsule. Then, the top of the target
capsule is cut off using a tubing cutter.
5. Pour the irradiated tellurium powder from the opened target capsule into the Vycor tube,
taking care to minimize spillage of the powder. The tellurium powder should dry and
pour freely from the target capsule.
6. Make a visual inspection of the capsule to be sure that all of the tellurium powder has
been transferred to the Vycor tube. Repeat the vibration process if there is any remaining
target material on the inner capsule walls.
7. Cap off the Vycor tube and place the Vycor tube on the furnace, then connect it to the
gooseneck and vacuum lines.
8. Position the stopcocks for distillation so that the vacuum pump is pumping in a direct
path to the Vycor tube. Turn on the vacuum pump, and establish a vacuum of at least –
28” of Hg on the gauge.
9. Physically and visually check all connection and valves in the distillation system to be
sure that they are secure and functioning properly.
10. Turn on the furnace, and observe the temperature controller to be sure that it is working
properly.
11. Set the temperature controller at 750oC.
12. Observe the furnace and the controller until the 750oC temperature is reached. At this
point, check operation of the distillation system by moving the controller set point up and
down slightly to ensure that the furnace turns on and off at the proper temperature. Also
recheck the vacuum connection at this point.
13. Periodically check the charcoal column trap with the radiation monitor in the hot cell to
ensure that I-131 activity is loading properly on the charcoal column trap.
14. When the run has been completed, turn off the furnace, maintain vacuum on the system
until the furnace has cooled down to no more than 200oC, and turn all valves in the
distillation system to the elution position.
15. Mount the loaded charcoal column trap in the ring stand, and read it with the radiation
monitor.
16. Wash the column with ~10 mL of sterile water for injection, collecting this water in a
water bottle. Check the water bottle with the radiation monitor to be sure that I-131
product activity is not being eluted.
17. Elute the column with sodium hydroxide 0.05N, collecting the I-131 produced in a
cleaned labeled glass bottle. Elute with 5 mL portions of sodium hydroxide 0.05N until
all significant activity has been removed from the charcoal column trap.
92
18. The tellurium breakthrough is checked by placing 3–4 grains of thioacetamide in a clean
25 mL beaker and send the beaker into the I-131 processing hot cell. To the beaker
containing thioacetamide is added 3 drops of I-131 product and the solution is swirled. If
the solution color change to grey/black, the resulting solution indicates the presence of
tellurium in the product, and the product must be rejected and disposed of in a capped
waste bottle containing absorbent material.
FIG. 1. 131I distillation system.
The dispensing of final product for assay and quality control is carried out by removing a 0.1–
0.2 mL of I-131 sample and placing it into 2 mL sample bottle, to be transported to the hood
or glove box inside a lead assay pig. From this sample two 20 lambda aliquots are removed to
prepare sample dilution to perform the bulk of the final product tests and the remaining
sample volume is used to performed a pH analysis using a strip of pH paper, with a range of
10.5 to 12.5. The pH results should be greater than 11.
Samples of the 20 lambda/50 mL dilution containing 4 drops of carrier solution, 10 mg I/mL,

are assayed for determination of I-131 concentration, I-133 concentration, radionuclidic
purity, and radiochemical purity.
Two dram vial for the determination of I-131 concentration are prepared by removing a
known amount aliquot of the 20 lambda/50 mL dilution, transferring each aliquot to a
separate 2 dram sample vial, and checking I-131 activity of both 2 dram vial with the Gamma
Ionization Chamber (GIC). The reading difference should not greater than 5%.
I-131 concentration assay is performed by (a) removing two 10 lambda aliquots from each 2
dram vial, (b) placing each aliquot onto a stainless steel counting planchet located in the
drying hood, (c) adding three drops of silver nitrate 0.1N solution to precipitate the iodine, (d)
drying the liquid on the planchets under heat lamp, and (e) counting all four sample planchets
placed into a plastic bag at the calibrated geometry on the GeLi multichannel analyser system.
The I-133 concentration determination is performed using one of the four planchet sources
93
prepared for the I-131 concentration determination on the GeLi detector system. The
radionuclidic purity determination is carried out by counting a 2 mL sample of the 20
lambda/50 mL dilution at the GeLi multichannel analyser system and analysing the spectra
for positive gamma emitters. The radiochemical purity is controlled by paper chromatography
utilizing one of the two dram sample vials, using 75% methanol as solvent.
The final product as sodium iodide, 131I, solution in NaOH, without reducing agents will be
used as 131I bulk solution for radiopharmaceuticals production. The specification of the final
product:
Physical appearance colorless solution.
Radioactive concentration >11.1 GBq (300 mCi) I-131/mL.
I-133 concentration d 0.80% of the I-131 concentration at assay time.
pH >11
Radionuclidic purity I-131 content >99.9%.
Radiochemical purity Iodide t 95%.
The ability to maintain vacuum on the system during the distillation process in separating
iodine from the irradiated tellurium is very critical and important. If the vacuum system
doesn’t work as expected, not only the distillation process will be uncontrollable, but also the
expensive Vycor will be broken.
BIBLIOGRAPHY
MEDI-PHYSICS INC., Manufacturing Manual of Radiochemical Iodine I-131, prepared for

the Radioisotope Production Centre, Indonesian National Atomic Energy Agency.
MEDI-PHYSICS INC., Quality Control Manual of Radiochemical Iodine I-131, prepared for
the Radioisotope Production Centre, Indonesian National Atomic Energy Agency.
94
Iodine-131(131I53)
Production scheme
Production of Iodine-131 radioisotope is usually performed in (n,J) nuclear reactions as

follows:
131
(a) Tem 82% E-, 30 h
130 131
Te(n,J) 18% I
131
(b) Te E-, 24.8 min
Cross-sections for (a) and (b) routes are 0.04 barn and 0.2 barn, respectively. As natural
tellurium contains 130Te nuclide in 34.48% there is no special need for using enriched
tellurium target. On the other hand, natural tellurium contains 126Te in 18.71%, which can
take part in the following nuclear reaction:
126 E decay
Te (n,J)127Te o 127
I(stable)
As a consequence of this, the 131I produced from natural tellurium cannot be considered as
carrier-free radioisotope and specific activity may play role in radiolabelling of organic
molecules. In order to attain sufficiently high yields of 131I as well as to simplify the
processing technology of the target, irradiation of tellurium can be recommended from point
of view of expedience. A wet method was earlier used for distillation of iodine, nowadays dry
distillation became wide-spread due to the higher yields and lower amount of radioactive
wastes.
As an alternative way extraction of Iodine-131 from uranium fission products may also be
considered. Since the uranium fission technology requires a rather complicated and expensive
facility, the tellurium irradiation would be the proper method for isotope production
laboratories established beside nuclear research reactors. Thus flow chart of the technology
based on tellurium dioxide irradiation is given as follows:

J. Környei,
Department of Radiochemistry, Institute of Isotopes Co., Ltd.,
H1121, Budapest, Konkoyl Thege WT-29.33, Hungary.
95
nat
TeO2, target
p irradiation in nuclear research reactor
131
Tem, 131Te
p cooling for E- decay to obtain 131I
131
I
p opening capsule, dry distillation of 131I from tellurium,
absorption in alkaline medium e.g. 0.05 M NaOH
131
I-sodium iodide solution
p dispensing, sterilizing, adding reducing agent in case of direct human use
131
I-sodium iodide solution as radiopharmaceutical, for direct use or for labelling
Target purity
Tellurium dioxide-mol.w. 159.60, content: >95%.

Faintly yellow powder. Identification of tellurium: by roentgenfluorescency.
Enrichment factor
Natural isotopic composition, 130Te content: 34.48%.
Impurity details
Lead: <0.002%, Copper: <0.0005%, Iron: <0.003%

Nickel: <0.0005% Silver: <0.0005%, Selenium:<0.0005%

120 122 123 124
Te: 0.0089%, Te: 2.46%, Te: 0.87%, Te: 4.61%,
125 126 128 130
Te: 6.99%, Te: 18.71%, Te: 31.79% Te: 34.48%
Supplier of target and grade: Fluka Chemie AG., Buchs, Schwitzerland, purum 02TE, product
number 86370, analytical data confirmed by certificate of analysis enclosed to the shipments.
Reactor
Nuclear research reactors with a neutron flux of 5 × 1012 – 1 × 1014 n/cm2/s can be used.
Higher fluxes should be avoided as the explosion of the target may occur due to the
generating heat and aerosols. Water cooling of the target within the irradiation channel,
during the whole irradiation, is necessary.
Capsule details
150 g tellurium dioxide powder is measured into a quartz tube and put into an electric
furnace. In a temperature range of 800–850oC the tellurium dioxide is melted and carefully
poured into an aluminium vessel (capsule) of dimensions diameter 22 mm and height: 90 mm.
96
The aluminium capsule is cooled by immersing in water while. Proper eye-guard and safety
gloves should be worn by the staff. After cooling to room temperature.
The capsule contains 140 g of melted tellurium dioxide.
The aluminium capsule containing the tellurium dioxide is placed into an aluminium
container possessing diameter of 30 mm and height of 110 mm. The container is closed by
welding. A lifting head, for handling the container in the irradiation channel, supplied with a
screw is fixed in the top of the container.
Fluxes up to 1 × 1014 n/cm2/s can be used, the higher flux results in higher yield of iodine-131.
At least 120 hours irradiation is requiered. It is worthwhile to extend the irradiation time up to
200 hours from point of view of higher yields however specific activities obtained decrease
slightly.
After irradiation a cooling period of 48 hours is required to complete E decay for obtaining
iodine-131.
Specific sctivities achieved and typical production yields/capsule
fluxes, 5 × 1012 3 × 1013 1 × 1014

n/cm2/s
Irradiation time, h 120 200 120 200 120 200
mass of target, g 140
Calculated yields, 53.79 81.68 322.79 490.13 1075.9 1633.7
after cooling, GBq
calculated specific 1113 1050 1120 1049 1120 1048
activity,
GBq/mg iodine
For iodine-131 production two hot cells under negative pressure, with manipulators, as well
as air ventilation system with iodine (aerosol) filter is required. Hot cells are made of iron
with a lead shielding of 15–20 cm. The window of the hot cell is made of lead glass with a
thickness of 40 cm. One hot cell is used for the distillation and absorption equipment, the
other is used for dilution, dispensing and sterilization of the 131I-sodium iodide solutions. The
cells and systems (e.g. radiation protection system, etc.) should correspond to the regulations
being valid for isotope laboratories of level "A".
Tellurium dioxide target
See above.
97
Sodium hydroxide
Sodium hydroxide white pellets, grade extra pure is used (DAB, Ph.Eur, BP). Identification is
performed by flame photometry. Drops coming from the aqueous solution of NaOH give a
bright yellow colour. Content determination is carried out by acidi-alkalimetric titration.
Sodium sulphate
Odour-free, colourless, transparent crystals or powder. Sodium gives bright yellow colour by
flame photometric analysis. Sulphate is identified when sodium sulphate is dissolved in 2 M
hydrochloric acid and barium chloride is added into it. White precipitation is formed. Limits
for impurities: Pb and Fe <10 µg/g, As <2 µg/g, K <1 mg/g, chloride <200 µg/g. By heating
at 130oC for 3 hours, rest should be 44.0–48.0%.
Sodium thiosulphate
Colourless transparent crystals. Sodium is identified by flame photometry. Thiosulphate is

identified by adding 2 M HCl. Sulphur should be precipitated. When adding 0.5 M silver
nitrate to the thiosulphate solution, white precipitation should be formed which will be turned
to yellow, brown and black. Limits for impurities: heavy metals <20 µg/g, As <5 µg/g,
chloride <50 µg/g. Content determination: titrating with iodine measuring solution: 1.00 mL
0.1 N measuring solution is equal to 24.817 mg sodium thiosulphate.
The irradiated container, delivered to the first hot cell, is opened by mechanical cutting. The
tellurium dioxide is crushed and filled into the vessel (1) of the distillation equipment, see
Fig. 1. The equipment, in addition, consists of a quartz bridge (2), acidic washing vessel (3)
and alkaline collectors (4a,b,c) are necessary to the distillation.Before starting glass beads are
filled into vessels (3) and (4c). In vessel (3) 40 mL 90% sulphuric acid is filled, while vessels
(4a,b,c) are filled with 0.05 M NaOH.
After assembling the distillation equipment, heating and vacuum is started. The melting point
of tellurium dioxide is attained within 30–60 minutes. Iodine-131 is collected in a collector
and is registered by the detectors. The distillation can be regarded as completed if the detector
and the recording unit do not indicate any further increase in radioactivity in the collector. pH
value of the collected solution should be higher than 8.
98
FIG. 1. Distillation equipment for 131I production.
Dispensing
The 131I-NaI solution is transferred to the second hot cell. The required radioactive
concentration is adjusted by adding 0.05 M NaOH and 0.01 M sodium sulphate solutions. If
the Iodine-131 solution is for direct human use (for thyroid diagnosis or for therapy),
maximum 2 mg/mL sodium thiosulphate solution is added into it. The activity is dispensed
into vials as required and sterilized by heat in an autoclave in the hot cell at 120oC for
30 minutes.
A vial containing 5-10 MBq I-131 sample is shielded by 0.5 mm lead foil. The detector is
positioned 30 cm far from the sample and the sample measured for 1000 seconds. Main
gamma-peak of I-131: 364.5 keV. Impurity limit: not more than 0,1% of other gamma
emitting impurities. A gamma-spectrum of Iodine-131 can be seen in Fig. 2.
99
FIG. 2. Gamma spectrum of 131I.
Paper-electrophoresis is used. Paper stripes, type Whatman No.3 MM for electrophoresis

having dimensions of 65 × 3 cm. Dropping of 10–20 µl samples takes place in a distance of
10- 13 cm from the end of the stripes. Borate buffer is used, concentration 9 g/l, pH=9 +/–0.1.
Electrophoresis is carried out on a potential of 900 V. Time: 50 min.
Rf values: product, i.e. iodide Rf = 0.7–0.9
impurities: iodate: Rf = 0.4
periodate: Rf = 0–0.1
elemental iod: Rf = 0
131
Product can be accepted if the I-iodide anion content is higher than 95% even on the
expiration date.
1. Physical observation: Clear, colourless solution.

2. Radionuclide identification: Iodine-131 radionuclide is identified by gamma spectrum
(see above characterization).
3. Radionuclidic purity: should be higher than, or equal to 99.9%.
5. Radiochemical purity: Measured by the above detailed electrophoresis, it should be
higher than 95%.
6. Concentration requierements:
The adjusted concentration depends on the application purpose.
a) Preparatum for labelling: >7400 MBq/mL
chemical content: 0.05 M NaOH and 0.01 M Na2SO4, reductant-free.
b) For thyroid diagnosis: 18.5 MBq/mL
chemical content: 0.05 M NaOH, 0.01 M Na2SO4 and 2 mg/mL Na2S2O3.
c) For thyroid therapy: >740 MBq/mL
chemical content:0.05 M NaOH, 0.01 M Na2SO4 and 2 mg/mL Na2S2O3.
100
7. Shelf life and recommended storage conditions:
8. Special comments of waste generated:
As Iodine-131 radionuclide is of relatively short half-life, wastes should be left to decay.
No special prescriptions are given, the normal radioactive waste tretament procedures
described for isotope laboratories should be applied. Do not let iodine-131 to be contacted
with acidic medium!
The distillation equipment is surely contaminated and should be dismounted by
manipulators in the hot cell. Acidic and alkaline solutions should be taken off into
separate vessels. The molten tellurium dioxide should be poured into a steel receiver. The
quartz bridge should be washed in 1 M NaOH and finally rinsed with water.
Dry distillation has been developed around 1980 and 131I has been manufactured by this
method since that time. Purity of products was always found over the given limits (>99.9%).
One of them, 129I may be present only in insignificant quantities (less than 1 × 10-5%). The
ventilated air coming from the hot cells of 131I production should be filtered by using a multilayer
filter that is capable of capturing radioactive aerosols as well.
BIBLIOGRAPHY
DEWANJEE, M.K. RAO, S.A., Principles of radioiodination and iodine labelled tracers,
Radiotracers for medical application, Vol. II, CRC Press, Boca Raton (1983).
FIRESTONE, R.B., Table of Isotopes, CD ROM Edition, (Shirley V.S., Chu S.Y., Eds.)
Version 1.0, Office of High Energy and Nuclear Physics, US Department of Energy (1996).
MONTESA, E., Production of iodine-131 by the wet distillation of tellurium dioxide, Philipp.
Nucl. J. 3 (1) (1975) 262.
MILLER, J., FÁBIÁN, GY., MÁNDLI, J., DORKÓ, GY., SASHEGYI, L., BIRÓ, GY., Dry
distillation method for iodine-131 production, Hungarian Patent No. 34.710 (1984).
SHIKATA, E., AMANO, H., Dry distillation of iodine-131 from several tellutium
compounds, J. Nucl. Sci. Tech., 10 (2) (1973) 80.
101
Iodine-131 (131I53)
E
130
Production scheme : Te (n,J) Te o 131I .
131
Target material : TeO2 99.99% pure, 100 mesh, CERAC incorporated

(treated by washing with distilled water and melting
at 700oC and then reground.).
Amount : 4 × 65 g.
Time of irradiation : 5–6 weeks (reactor working 40 MW-h/week at 1.2
MW).
Average neutron flux : About 1.78 × 1013 n/cm2/s.
Target container : Aluminium container (Japan Industrial standard JIS
grade A-1050 purity 99.5%) sealed by cold welding
(700 kg/cm2).
Production yield : 192 GBq (5.2 Ci).
Production route
1. TeO2 target purification, preparation and testing.

2. Target canning.
- cleaning aluminium container.
- compacted 65 g TeO2 target in aluminium container
- cold welding of aluminium container.
- leak testing by bubble test.
3. Irradiation for 5–6 weeks.
4. Unloading target from reactor core and transfer to production cell.
5. Production process by dry distillation at 700oC.
6. Bulk product collected in 10 mL vial.
7. Transfer bulk product from production cell to dispensing cell and measurement of total
activity.
8. Sampling product for processing of quality control.
9. Processing of dilution and dispensing.
10. Activity measurement from each dispensing.
11. Capping vial with aluminium cap, washing with water and let it dry.
12. Transfer vial of product from dispensing cell into lead pot.
13. Packaging.
14. Final survey of contamination and dose rate exposure.
15. Deliver to customer.

G. Aungurarat,
Isotope Production Division, Office of Atomic Energy for Peace,
Bangkok, Thailand.
102
A flow chart of the operations and 131I production apparatus.
Procedure of 131 I production
1. Charge TeO2 irradiated target in furnace.

2. Fill I-131 trap, T1, T2, with buffer solution.
3. Operate pump 1 for carrying Iodine vapor to T1, T2 trap, releasing air from pump 1,
trapped in bubble counter contained NaOH.
4. Increase temperature of furnace to 700oC.
5. TeO2 trap, trapped some TeO2 powder from furnace.
6. After 1 h. at 700oC lower temperature of furnace to 200oC and operate pump 2 for
carrying Iodine vapor that leak from furnace into containment absorped in process filter
and releasing air from pump 2, trapped in bubble counter.
7. Turn off pump 2, open a containment transfer the spent target out of furnace and make a
new charge of target.
8. Final product in T1, T2 collected in 10 mL vial.
Specify target purity
Specific analysis
TeO2 - 99.99% pure (79.62% Te)
- 100 mesh
X ray diffraction analysis
TeO2 - paratellurite, tetragonal
103
Enrichment factor if applicable
Impurity details
Element Results
Na <1 ppm
Al <0.001%
Ca <0.001%
Cu <0.001%
Fe <0.001%
Mg <0.001%
Sb <0.002%
Se <0.002 5
Si <0.001%
Ti <0.001%
Supplier : Cerac incorporated

P.O. Box 1178, Milwankee, WI 53201-1178
Tel: (414) 289–9800
Fax: (414) 289–9805
Purification of tellurium dioxide
Attention: Tellurium dioxide is a toxic substance!
The quality of the tellurium dioxide from diverse origins varies significantly. A purification as
indispensable due to impurities such as nitric acid and others.
1. Take up to 2 kg. customary TeO2 into a glass-filter funnel and wash it by at least two liters
distilled water until the wash-water shows a pH neutral reaction.
2. Dry the TeO2 in the covered glass-filter funnel over night.
3. Transfer the moderate wet TeO2 into porcelain crucibles, dry it carefully at 100 to 150oC
and then melt it for about 1 hour in order to evaporate any volatile impurity as e.g. Cool
down and repeat the wash procedure if brown nitrous gases are vigorously released during
the melting procedure.
4. After cooling break the TeO2, which often shows green or yellow-brown colour.
5. Remove the crucible fragments.
6. Grind the TeO2 lumps in a ball mill and separate the powder by a sieve (0.100 mm).
7. Test a powder sample for constant weight after heating at 150oC.
8. Test another powder sample by a could test-run in the furnace cell: the absorption solution
in the first winding absorber of the iodine traps must stay at neutral pH.
If the test was satisfactory the TeO2 powder can be used as target material.
1. Reactor used and which assembly (hydraulic tube, etc.)

Facilities for Primary Radioisotope Production
Research Reactor : TRIGA Mark III
Reactor power : 2 MW (Operate at 1.2 MW)
Operating period : 40 MW-h /week. (Wed = 12 h, Thur = 12 h, Fri = 10 h).
104
Irradiation position Thermal neutron flux
n/cm2/s
CT 3.1 × 1013
C8 2.5 × 1013
C12 2.5 × 1013
G5 1.2 × 1013
G6 1.0 × 1013
G32 0.98 × 1013
G33 1.2 × 1013
2. Capsule details (material, dimension, encapsulation method, etc.) any special precautions
for target encapsulation (degassing, low pressure, etc,)
- Material : Aluminium Japan Industrail Standard (JIS)
grade A-1050 purity 99.5%
- Dimension : OD 22 mm, ID 19 mm, L 12.5 cm
- Encapsulation method : Cold welding at pressure 700 kg/cm2.
- Leak testing : Bubble test with acetone.
Note: Special precaution for target encapsulation is the cleaning of Al-container.
Step of cleaning procedure
– Aluminium can.
– Soaking in acetone solvent for removing organic substance (24 h), let it dry.
– cleaning with 10% NaOH (15 min).
– Rinsing with clean water.
– Dipping into 30% HNO3 (1–2 min).
– Rinsing with clean water.
– Rinsing with distilled water.
– Drying at 105oC (1 h).
3. Mass of target per capsule.
65 g. of TeO2/capsule.
4. Preparation of target for encapsulation, reactor irradiation parameters (flux, irradiation
time, etc.).
- Preparation of target for encapsulation. TeO2 in Powder form (100 mesh) is compacted
in Al. Container and sealed by cold welding method (700 kg/cm2).
- Reactor irradiation parameters.;
Reactor Power : Operate at 1.2 MW
Operating period : 40 MW-h/week (wed = 12 h., Thur = 12 h, Fti = 10 h)
Neutron flux : average 1.78 × 1013 n/cm2/s
Irradiation time : average 5 weeks by rotating position of irradiation from
G o C o CT.
5. Specific activity achieved and typical production yield per capsule.
11 GBq (1.3 Ci)/capsule (65 g. TeO2).
6. Any other pertinent information.
– Two cells boxes of stainless steel sheets (x 8 CrNiTi 18.10) of 0.2 mm. thickness,
dimension l 1850 mm. w 855 mm. h 1510 mm. Use for Production cell and dispensing
cell.
– A channel l 200 mm., w 220 mm., h 340 mm. Connects the two cell boxes.
105
– Shielding
Front 100 mm. Pb.
Side 100 mm. Pb.
Back 50 mm. Pb.
Roof 30 mm. Pb.
– Four lead-glass windows 300 × 300 mm. 220 mm. thickness, density 3.6 g /cm3
– 8 Ball tongs.
– Conditional Processing:
negative pressure — 150 Pa.
exhaust fan 48 m3/h (1.7 m /s).
– Special filters in the exhaust line is siliga gel treated with silver nitrate and maintain at
60–90oC.
– Dose rate monitor.
Adjustable alarm threshold 0 to 50 µGy/h.
– Under pressure gauge and under pressure monitor.
The under pressure monitor gives optic and acoustic signals if the actual under pressure in the
cell box drop to less than — 50 Pa.
Analysis of raw material (TeO2)
Method : Polarography
Voltage : - 980 mV
Supporting electrolyte : 0.5 (NH4)2SO4 + 0.004 M Na2EDTA.
Analysis of Te in 131I
Method : Spot Test (see the description on page no. 114)

Limit : Te d 10 ppm.
The irradiated tellurium dioxide is transferred into 50 mL porcelain crucible (65 g of

TeO2/crucible). Put the crucibles into the furnace. Start the furnace an increase the
temperature and maintain at 700oC for 60 minutes. Simultaneously apply a stream of air by
vacuum pump with a flow rate 20–80 l/h pass through the furnace and iodine traps. The
iodine vapor will be absorbed in NaHCO3/Na2CO3* buffer solution which contained in the
iodine traps. The product is drained from the traps into the vial and ready for activity
measurement and dispensing.
Note: * = Buffer solution preparation:
A tenfold concentrated buffer solution can be prepared in a 500 mL batch and stored in a
closed flask for a certain period. The required volume of buffer solution must be freshly
prepared immediately before use by dilution of the tenfold concentrated buffer solution and
succeeding filtration.
1. Take 8.0 g NaHCO3 (AR) and 4.35 g Na3CO3 (AR) into a 500 mL volumetric flask, add
water and shake thoroughly for dissolving.
2. Fill up after complete dissolving to 500 mL with tridistilled water.
106
3. Filter through a glass-filter funnel (fritte G 3 average pore diameter 15 to
40 micrometers) into a clean storage flask. Thus the tenfold concentrated solution is
obtained and can stored in the closed flask for a certain period.
4. Immediately before use dilute the required volume of the concentrated buffer solution by
tridistilled water in a ratio 1: 9 and filter again through a glass-filter funnel G 3 into a
clean 20 mL vial. Close the vial by a rubber stopper and transfer it into the production
cell.
Radiopharmaceutical finished product analytical procedures
Product : Sodium Iodide (I-131).

PH : The pH must be 8.0 to 10.0.
Procedure : The pH of the sample is measured using an appropriate indicator paper.
Appearance : A clear colorless solution.
The radioactive concentration is measured at 1.00 p.m. hours on the date specified on the
label. Sodium iodide (I-131) contains not less than 90.0% and not more than 110.0% at the
date and hour stated on the label. The activities of the product available are not less than
25.0 mCi per mL.
Procedure
The sample in a sealed and capped vial is measured in an ionization chamber detector, the
activity is calibrated using an appropriate factor. Decay factor and volume correction.
Iodine-131 decays by beta and gamma emissions with physical half-life of 8.04 days. The
main photopeaks are 80.02 (2.2%) 284.3 (6.3%) 364.5 (79.0%) 639.9 (9.3%) and 722.9
(2.8%) keV.
Procedure
Using the NBS mixed standard No. 4275C-90 contained with 154Eu, 155Eu, 125Sb and the
OMNIGAM package for calibration of HPGe detector equipped Multichannel Analyser. The
radionuclidic purity is determined by measured the small amount of sodium iodide (I-131) in
the same geometry of the calibrated standard. The quantity is expressed in kBq and the five
photopeaks are presented.
The radiochemical purity is not less than 95.0% of iodide ion.
Reagent
Sodium carbonate solution 0.05 M. Sodium carbonate (AR) 5.29 g is dissolved in 1,000 mL
of distilled water.
Palladium chloride solution 0.1%. Palladium chloride (AR) 0.1 g is dissolved in 100 mL of
methanol.
Instrument.
107
EC Power Supply Model EC-500 and Gelman Electrophoresis Chamber Raytest Scanner
Model Gita-92 Thin-layer Chromatorgraphy Analyser.
Paper
Whatman No. 1 (40 × 300 mm.)
Procedure
1. Whatman paper is dipped in the Sodium carbonate solution.
2. Place a measured volume of solution containing 100 mg of potassium iodide. 200 mg of
potassium iodate and 1 g of sodium bicarbonate in each 100 mL. 50 mm. from one end of
the strip.
3. Add a similar volume of appropriate sodium iodide I-131 solution which count rate about
20,000 counts per sec.
4. Develop the chromatographic strip in electrophoresis chamber using high voltage
240 volts (8 volts/cm.). 60 min. The cathode is at the origin.
5. Dry the chromatogram in air, and determine the radioactive distribution by scanning with
Na (Tl) detector equipped with Raytest Scanner. The radioactivity of the iodide 131I band
is not less than 95.0% of the total radioactivity and its Rf values about 0.7 while the Rf
value of 131IO3 is about 0.4.
6. Confirm the identity of the iodide band by spraying with PdCl2 solution. The
development of a brown color indicates the presence of iodide ions.
Chemical purity
The tellurium content is not more than 10 ppm.

Reagent
Standard tellurium solution 10.0 ppm. Stock solution of tellurium 1,000 ppm. is prepared by
dissolving 125.0862 mg of tellurium dioxide in 100 mL of distilled water. The stock solution
is diluted with distilled water to prepare the standard solution with concentration of 10.0 ppm.
Stannous chloride solution 5.0% (fresh preparation). Stannous chloride dihydrate
(SnCl2.2H2O) 0.25 g is dissolved in 0.25 mL of concentrated hydrochloric acid, heated to the
clear solution and diluted to 5 mL with distilled water.
Sodium hydroxide solution 25.0%. Sodium hydroxide 25 g is dissolved in 100 mL of distilled
water.
Saturated sodium carbonate solution
Procedure
1. Place one drop of standard tellurium solution, water (blank) and sodium iodide (sample)
solution into each hole of spot plate.
2. Add one drop of stannous chloride, saturated sodium carbonate and 25.0% of sodium
hydroxide solution respectively.
3. Compare the black precipitation of Te metal from the sample with standard Te and blank.
(Te4+ is reduced by Sn2+ to give the tellurium metal). If there is preservative such as
sodium thiosulfate (Na2S2O3) in the sample solution, it will give the dark brown
precipitation together with Te metal.
The intened use of the final product is for oral and some labeled compound preparation.
108
Sodium iodide (I-131)
Product specification
Chemical form: Sodium iodide (I-131) in carbonate buffer pH 8.0–10.0.

Appearance: A clear colorless solution.
Radionuclide: Iodine-131 contains not less than 95.0% of the labeled amount of 131I as iodide
expressd in megabecquerels (microcuiries or millicuries) per milliliter at the time indicated in
the labeling.
Chemical purity: For dry distilltion process, sodium iodide (I-131) in carbonate buffer
solution contains not more than 10.0 ppm. of tellurium.
Radionuclidic Purity: 131I decays by beta and gamma emission with a physical half-life of
8.06 days. The principle beta mean energy is 192 keV (90.0%), and the major photopeak of
gamma emission is 364 keV (79.0%).
pH: Between 8.0 and 10.0.
Radiochemical purity: More than 95.0% of the 131I presented as iodide ion.
Radioactive concentration: Not less than 925 MBq (25 mCi) of 131I per mL at hours and date
specified on the label.
Expiry: Two weeks after manufacturing date.
Packaging: Ten mL vial sealed with a rubber stopper and aluminium seal. Package in a
25 mm. thick lead shielding.
Special comments on disposal of waste generated.
The advantage of dry distillation method is less liquid waste from the process. The liquid
waste is only came from water for cleaning cell box, vial, iodine traps and dispensing unit
which can be drained directly to a tank under the cell and leave for decay.
Solid waste of Al container, paper etc. is collected in the cell box for decay and disposed to
the waste management facility.
Spent TeO2 target is collected in 5 litre can, stored for decay. After decay for 3–5 year, it can
be reprocessed and reused.
Preparation and cleanup of the facility and preparation for processing of next production
batch:
– cleaning iodine traps and dispensing unit with distill water.
– clean the floor of cell box which should be free from TeO2 powder.
– check every production system and equipment which should be in the proper function
ready to work.
– The booting of ball tong used in I-131 production cell should be able to resist penetration
of iodocompounds. As some iodo-compounds can penetrate rubber booting and leak into
the operating room.
– The iodine up to three production runs can be absorbed into the same absorption solution
in order to produce a higher concentration of radio-iodine solution.
BIBLIOGRAPHY
BEYER, J.J., ET AL., Isotope Production Technology I-131 Iodine Production Line Part I,
Rossendorf. Dresdren, Germany.
EG & ORTEC, Gamma VisionTM. Gamma ray Spectrum Analysis and MCA Emulation for
Microsoft Windows 3x and Microsoft Windows for Workgroups A66-BI, Software User
Manual, Software Version 2.4, Ortec Part No. 762880, Manual Revision F, USA.
109
EUROPEAN PHARMACOPEIA COMMISSION, Public Health Committee European
Pharmacopeia Commission, Group of Expets No. 14 (Radioactive Compounds). Council of
Europe, 5th revision (1985).
FEIGL, F., Spot Tests in Inorganic Analysis, 5th edition, Elsevier Publishing Company, Rio
de Janeiro (1958) 600.
INTERNATIONAL ATOMIC ENERGY AGENCY, Radioisotope Production and Quality
Control, Technical Report Series No. 128, Vienna (1971) 968.
PHAN, T., WANICH, R., Practical Nuclear Pharmacy, 2nd edition, Banyan Enterprises Ltd.,
Lit Fresenius, Z. Te determination by polarography and CSV., Anal. Chem. 295 (1981) 1–6.
UNITED STATE PHARMACOPEIA CONVENTION, INC., 21st Revision, Mack Printing
Company, Easton, USA (1985).
110
Iodine-131 (131I53)
(Fission product)
235
Production scheme : U (n,f) 131I
Target plate manufacture
Target plate irradiation
Target plate dissolution
Extraction and separation of

molybdenum and iodine
Iodine processing
continued separately
FIG. 1. I-131 Process flow sheet.
The targets for fission I-131 production are the same as for 99Mo, viz. an uranium/aluminium
alloy (containing U enriched to 45% 235U) clad in aluminium. It contains 4.2 g 235U in a 200
mm × 45 mm target plate manufactured by the NECSA of SA. Only very low levels of
impurities which could act as neutron poisons are allowed.
Irradiation parameters
Irradiation is done in in-core irradiation in the 20 MW SAFARI-1 research reactor at

Pelindaba near Pretoria. SAFARI-1 is a tank-in-pool type light water reactor of Oak Ridge
design. Six dedicated positions are equipped with thimble tubes which allow for the insertion
and retrieval of target plates with the reactor on power. A maximum of seven target plates in
an aluminium plate holder can be irradiated per position for a period of up to 200 hours,
depending on customer demand. The average thermal neutron flux is 1.5 × 1014 n/cm2/s at
20 MW. After irradiation the target plates are stored in the reactor pool for up to 24 hours to
allow for the decay in gamma heating and short lived fission products. After 99Mo extraction
the iodine nuclides are stored on a resin column for at least 10 days before being extracted
and purified. The maximum 131I activity available per plate (after storage) for maximum
irradiation conditions is 3.3 × 106 MBq (90 Ci).

W. Van Zyl de Villiers,
The South African Nuclear Energy Corporation, Ltd.,
Bldg. 1900, PO Box 582, Pretoria 0001,
South Africa.
111
Processing facility
A typical production line of four shielded hot cells consists of the following:
– an elution cell in which the first ion exchange column from the 99Mo process is eluted as
well as waste tank under the cell floor for the accumulation of liquid waste. The dissolver
cell of the of the 99Mo process can also be used to elute the 131I from the stored resin
column;
– a purification cell containing the distillation apparatus;
– a dispensing cell containing an ionization chamber for the quantification of the product
and the dispensing thereof according to client needs; and
– a packaging cell where the product bottles are placed into transport containers, labelled
and removed for shipment to the client.
The 131I production hot cells are served by a dedicated ventilation system, keeping the cells
under slight negative pressure relative to the surrounding areas. It is an once-through system
to prevent any build-up of process gases. There is 100% back-up with respect to the extraction
as well as the primary filtration system, and the system is coupled to emergency diesel
generator and uninterrupted power supply standby systems.
Dedicated filtration is provided for aerosols (HEPA filters), iodine (specially impregnated
activated carbon filter beds) and noble gases which are realized during dissolution of the
target plates (activated carbon filter banks). The dissolution rate of target plates, during which
hydrogen is formed, is controlled in such a way that the hydrogen concentration in the
ventilation system is within safety limits. In addition the I-131 purification and dispensing
cells contain in-cell impregnated activated carbon filters to trap volatile iodine at low flow
speeds.
Monitoring systems for noble gases, iodine, alpha and beta/gamma emitters as well as
hydrogen are distributed throughout the ventilation system for process control measures as
well as the quantification of releases to the environment as part of application of the ALARA
principle.
The materials and reagents used in the extraction and purification of 131I are prepared in a
dedicated laboratory consisting of a quarantine holding area, a section for storage of approved
materials and reagents, and a processing area where chemicals and reagents are prepared.
Raw materials received from suppliers are placed in quarantine, and released for further use
only after being tested for compliance with specified requirements. Bulk reagents prepared
from approved raw chemicals are tested (where applicable) for functionality and
concentration. These reagents are also placed in quarantine directly after preparation, and
released only when verified to comply with specification. Process reagents are made up and
transferred to the 131I processing facility in quantities just enough for each production run.
A typical specification for the concentration of process reagents is ±10%. Analytical methods
such as atomic absorption spectrometry, titrimetry and ion chromatography, with precision
and accuracy typically 1–4%, are used in the analysis of process reagents.
112
FIG. 2. Process scheme for I-131 extraction and purification.
Chemical processing
Irradiated target plates are dissolved in concentrated NaOH. A suitable oxidizing agent is
added to ensure that all molybdenum is dissolved, while at the same time leaving the non-
fissioned uranium as a solid residue for recovery at a later stage. Nuclides of only a few
elements are dissolved with molybdenum, and the purification steps following dissolution
have been designed to specifically ensure proper decontamination of Mo and I (in separate
production streams) with respect to these elements, while also giving good product recovery.
Purification of iodine is carried out by means of an anion exchange resin and a distillation
step. The first purification step consists of sorption of I, treating the resin column with a
storage solution and storing it for a suitable decay period, followed by elution of I from the
column. In the second step the eluate is distilled and collected in a solution as specified by the
client, or in a related NaOH solution which is adjusted to the client’s specifications
afterwards.
Apart from the above mentioned control measures regarding process reagents, the distillation
rate as well as the flow rate through ion exchange columns is controlled and monitored.
Progress is monitored through observation of colour changes and by means of analysis of pre-
distillation samples. All actions are carried out according to prescribed work instructions for
the operators.
The 131I product is dispensed according to clients’ requirements based on the bulk activity
measured in the third hot cell and the particular precalibration period. Assaying is done by
means of a frequently calibrated ionization chamber. Radioactive concentration (MBq.cm-3) is
calculated from the product activity and the final volume of product solution. The final mass
is also reported to the client.
113
Quality control testing of the final 131I product is geared to provide a certificate of compliance
within 48 hours of the dispensing of each production run. This demonstrates that the product
is within specifications and is reported in a “less than” format.
Radionuclidic purity of 131I is determined through the following measurements in a separate

dedicated laboratory:
– J spectrometric determination of 131I activity by using a calibrated high purity Ge
detector;
– J spectrometric determination of gamma emitting impurities that are present. From the
pulse height spectrum activities for selected nuclides (based on decay and chemical
criteria) are determined. For nuclides not found in the spectrum minimum detectable
activities are calculated;
– D and pure E emitting nuclides (e.g. 89Sr, 90Sr/Y and 99Tc) are not analysed for an a
routine basis. Information is available on a once-off test of a 110 day decay sample (to
diminish the effect of the E particle from 131I) to verify that the product is free of D and E-
emitting nuclides as well as Sr nuclides.
Radiochemical purity of 131I is determined by means of adsorption chromatography on a silica

gel column. The iodine species are separated due to their different affinities for eluting agents.
The column is washed with carbon tetrachloride, acetone and water and the activity in each
elute is measured by J-spectrometry.
Fission 131I, which is produced as described above, is used for the production of Na131I
capsules and solution. The final 131I product complies with the specifications derived from
European, British and United States Pharmacopoeia specifications for Sodium Iodine-131I:
Not less than 99.9% of the total radioactivity is due to 131I and not more than 0.1% of the total
radioactivity is due to 133I, 135I and other impurities.
Other nuclides
95
Nb:131I <1 × 10-3
95
Zr:131I <1 × 10-3
132 131
I: I <1 × 10-3
133 131
I: I <1 × 10-3
Nuclides not
specified Not detected
>95% as iodine (I).
t1 Ci(3.7 × 1010 Bq)/cm3 at calibration time.
114
Product solvent
0.05 M NaOH, with a client specified reducing agent and buffer solution.
Calibration date
3 to 8 days after production.
Shelf-life
30 days after production.
Waste management
All process consumables such as pipes, ion exchange columns and reagent containers are used
for only one production run. After each run, these are collected and stored to allow for decay
of the short-lived nuclides with which it is contaminated. This is followed by compaction and
disposal as low level waste.
Alkaline liquid waste is accumulated in shielded stainless steel tanks for later immobilization
in a cement-vermiculite or left to decay for treatment with other on-site low-level liquid
waste.
Hot cell off gas is treated by adsorption and filtration as described above.
Being a raw material for medical end use, it is absolutely imperative that all aspects of fission
131
I production are covered by a quality assurance programme. The latter should conform to
an internationally accepted code of practice for quality systems, e.g. ISO 9002, as well as
other requirements such as Good Manufacturing Practice according to 21 CFR Parts 210 and
211. Particularly important aspects are quality control of process consumables, strict control
of the chemical purification process and purity certification of the final product.
Radiological and environmental monitoring as well as thorough waste management practices

are critically important to ensure adherence to the ALARA principle and to minimize the
environmental impact of production activities.
Drug Master Files have to be submitted to the pharmaceutical regulatory authorities in the
countries where the product will be used in Na131I capsules, solution and other products.
115
Iridium-192 (192Ir77)
Half-life : 73.83 d
Metastable 1 (m1): 1.45 min (~100% IT)
Metastable 2 (m2): 241 a
191 192
Production scheme : 77 Ir (n, J) 77 Ir
Target material : Na2 IrCl6 (Koch Light /Fluka) (GR/AR)
Reaction Isotopic Cross Activity of element at Secondary reactions

Abundance Section 1012 n/cm2/s. And properties of
of barn One Four Satu- Nuclide formed
nuclide% week Weeks ration
23
191
Ir (n, J) 192
Ir 37.3 954 ±10 68 250 1 Na (n, J) 24Na
77 77
(Vg = 309 GBq GBq TBq Half-life: 14.95 h
Vm1 = 695 (1.85 (6.73 (28.9 Isotope Abundance 100%
Vm2 = 0.16) Ci)/g Ci)/g Ci)/g V =0.53 b
Ir Ir Ir
35
Cl (n, J) 36 Cl
Half-life: 3.01 × 105Y
Isotope Abundance
75.77%
V =43.6 barns
35
Cl (n, p) 35S
Half-life: 87.5 d
Isotope Abundance
75.77%
V = 0.48 barn
37
Cl (n, J) 38Cl
Half-life: 37.24 minutes
Isotope Abundance
24.23%
V = 0.43 barn
E- 0.259 5.6% Gamma 0.2058 3.34%

0.539 41% 0.296 28.7% IC 2.5%
0.675 48% 0.3084 29.7% 2.5%
EC 4.6% 0.3165 82.71% 5.7%

0.4681 47.8% 1.5%
0.4846 3.19%
0.5886 4.52%
0.6044 8.18%

M. Ananthakrishnan,
116
Target material Koch Light/Fluka Na2IrCl6 10 mg (AR/GR).
Container Standard 1S aluminium can 22 mm dia and 44 mm ht. cold

weld sealed.
Irradiation One week .
Type of facility for Standard glove box 6 feet × 4 feet × 6 feet with 4 inch lead
processing shielding- under negative pressure.
Flux 1-1.5 × 1013 n/cm2/s.
Chemical process
The can is opened and the irradiated target transferred to a 100 mL beaker. 10 mL 0.1 N HCl
is added to it and the solution stirred to complete the dissolution of target.
Radioactive concentration: An aliquot of the product solution is measured for radioactive

concentration in a well type ionization chamber standardized with 226Ra.
Radio nuclide purity is determined by gamma ray spectrometer (MCA) Specific activity is
determined by the known weight of target taken for Irradiation.
Characteristics of solution
Chemical form Na2 Ir Cl6 in dilute HCl solution.
Radiochemical concentration 74–370 MBq/mL.
Specific activity >185 GBq/g Ir.
Acidity Approx. 0.1 N with respect to. HCl.
117
Iron-59 (59Fe26)
Half-life : 44.5 d
58
Production scheme : Fe (n,J) 59Fe V = 1.155 b
Decay energy : E (MeV) J (MeV)

0.273 (45.3%) 0.1923 (3.08%)
0.463 (53.1%) 1.099 (56.5%)
1.566 (0.18%) 1.291 (43.2%)
0.130 (1.31%)
Iron-59 is reactor-produced by the radiative (n,J) reaction on enriched (>60%) iron-58 ferric
oxide targets.
FIG. 1. Calculated production yields of iron-59 by neutron irradiation of nickel targets as a

Enriched iron oxide targets (i.e. only 0.28% natural abundance) are used. The projected
production yields of iron-59 from irradiation of enriched iron-58 as a function of irradiation
time at various thermal neutron flux values are shown in Fig. 1.

Oak Ridge, Tennessee 37830-6229, USA.
118
Processing of iron-59 produced from enriched iron-58 ferric oxide targets (from ORNL
radioisotopes procedure manual, ORNL-3633, 1964)
1. The following equipment should be prepared: 100 mL product bottle, 50 mL Vycor

beaker, 1 liter separatory funnel, 150 mL Pyrex beaker, 250 mL separatory funnel and the
hot off-gas scrubber unit.
2. Open irradiation can and transfer contents to 150 mL Pyrex beaker.
3. Add 10 to 20 mL of 12 M HCI and heat solution on hot plate under hot off-gas scrubber
assembly. Adjust solution to ~100 mL of 9 M HCI solution to prepare for extraction of
54 54
Mn (i.e. from any Fe activation).
4. Equilibrate 500 mL of dichlorodiethyl ether with 9 M HCI by shaking in a 1 liter

separatory funnel for 10 min. Separate the HCI wash and hold the ether for extraction of
59
Fe solution.
5. Transfer the 9 M HCI solution containing the 59Fe into 250 mL separatory funnel and add
an equal volume of HCI-washed dichlorodiethyl ether. Agitate for 10 min and separate
the two phases. Iron-59 is extracted into the organic phase.
6. Repeat the extraction procedure twice.
7. Collect ether fractions and extract with 50 mL of distilled H2O. This step removes all
59
Fe from aqueous solution. Iron-59 is extracted into aqueous phase.
8. Repeat water wash with 10-min agitation periods until all 59Fe is removed from organic
phase. Three extractions are usually sufficient.
9. Collect water wash in a 50 mL Vycor beaker and evaporate to dryness under hot off-gas
assembly.
10. Fuming the product with 16 M HNO3 removes any organic compounds which may be
present.
11. Fume twice with 12 M HCI to completely decompose the HNO3.
12. Dissolve residue in 50 mL of 1 M HCI and transfer to product bottle. Product should be
clear and yellow-colored solution.
Molarity of HCI
Total solids
55
Fe concentration
59
Fe concentration
60
Co concentration.
119
The final product should be analysed by gamma spectroscopy and is provided as the chloride
in HCl solution.

59 55
The product is provided as the chloride in HCl solution — Fe >99% (exlcusive of Fe) and
55
Fe <5%.
Iron-59 had been produced at ORNL with a specific activity of about 16 mCi/mg. A typical
14
production run consisted of irradiation of a 10 mg for 30 minutes at a flux of 2 × 10 . The
processing yields are >95%.
BIBLIOGRAPHY

120
Lutetium-177 (177Lu71)
Half-life : 6.734 d
176
Production scheme : Lu (n,J) 177Lu
Lutetium-177 (maximal beta energy of 0.497 MeV) is an useful lanthanide +3 metal for
various therapeutic application. Because of a rather large cross-section, lutetium-177 can be
directly reactor-produced (Fig. 1) with relatively high specific activity by neutron capture of
enriched lutetium-176. Because of the relatively low 2.6% natural abundance, enriched
lutetium-176 (i.e. >70%) target material is required for this production route. As an alternative
production route, carrier-free lutetium-177 can be obtained carrier-free from beta decay
(indirect production) of ytterbium-177 produced by neutron capture of enriched ytterbium-
176.
For direct production, enriched lutetium-176 oxide targets are used.
The production of lutetium-177 by direct (n,J) activation of enriched lutetium-176 as a

function of irradiation time for various thermal neutron flux values is illustrated in Fig. 1.
FIG. 1. The projected direct production of lutetium-177 from neutron irradiation of enriched
lutetium-176 as a function of irradiation time for various thermal neutron flux values.

Nuclear Medicine Programme
Oak Ridge, Tennessee 37830-6229, USA
121
177 177
FIG. 2. Indirect production of Lu illustrating the theoretical yields of Yb and 177Lu as a
function of irradiation time in hydraulic position of # 5 of the ORNL High Flux Isotope
15 2
Reactor; (Ith = 2.05 × 10 n/cm /s).
These initial irradiation studies conducted at ORNL did not involve chemical processing and
irradiated samples were counted directly. Efficient techniques for the separation of carrier-
free lutetium-177 from the irradiated ytterbium-166 targets would have to be developed.
The product should be analysed by gamma spectroscopy.
The specific activity of lutetium-177 directly produced from enriched lutetium-176 may be
limited by the irradiation periods required to minimize the production of the long-lived
177m
Lu produced by the competing lutetium-176(n,J)lutetium-177m reaction. For these
reasons the indirect route provides the highest radiochemically pure lutetium-177.
122
177m 177
FIG. 3. The ratio of Lu/ Lu as a function of irradiation time in hydraulic position # 4 or
15 2
6 of the ORNL High Flux Isotope Reactor (Ith = 1.76 × 10 n/cm /s).
BIBLIOGRAPHY
OAK RIDGE NATIONAL LABORATORY, Nuclear Medicine Program Progress Report #

ORNL/TM-13107 (1995).
123
Lutetium-177 (177Lu71)
Half-life : 6.734 d (177gLu)

176
Production scheme : Lu (n,J) 177Lu Vg = 1770 b, Vm = 317 b
177m
Lu: 160.4 d
(78.3% E-, 21.7% IT)
Type of decay, and energy (keV)
Beta 176.5 (12.2%) Gamma 71.65 (0.15%)

(E- max. energy) 248.5 (0.053%) 112.95 (6.4%)
384.8 (9.1%) 136.7 (0.05%)
497.8 (78.6%) 208.37 (11.06%)
249.67 (0.21%)
321.32 (0.22%)
177
Decay product : Hf
Production process
Radioactive 177Lu is produced by the 176Lu (n,J) 177Lu reaction in a Lu2O3 target and is
prepared as 177LuCl3 in HCl solution. After irradiation, the target is decayed for 3 days for
reduction of activity of 176mLu (half-life 3.664 h) produced by the side reaction.
Procedures
Capsuling, Neutron irradiation, Cooling, Decanning, Gross-activity measurement, Chemical

treatment, Inspection, Stock.
Target purity
Lu2O3 99.99%
Enrichment factor if applicable
(None)
Impurity details
Y2O3 < 5 ppm, CeO3 < 5 ppm, Pr2O3 < 5 ppm, Nd2O3 < 5 ppm, Sm2O3 15 ppm,
EuO3 < 5 ppm, Gd2O3 14 ppm, Tb2O3 < 5 ppm, Dy2O3 < 5 ppm, Ho2O3 < 5 ppm,
Er2O3 < 5 ppm, Tm2O3 < 7 ppm, Yb2O3 22 ppm, La2O3 < 5 ppm, CaO 30 ppm,
Fe2O3 < 5 ppm, SiO2 30 ppm.

H. Takahashi,
Isotope Division, Japan Atomic Energy Research Institute,
Tokai, Ibaraki, Japan.
124
Natural abundance
Rare Metallic Co., Ltd., Japan
White powder of Lu2O3 99.99%.
Reactor used and which assembly
JRR-3M, Hydraulic tube.
Capsule details
The target is sealed in a quartz ampoule (outer diameter: 10 mm, inner diameter: 8 mm,
length: 50 mm) which is in a cold-pressure-weld type cylindrical aluminium can (Outer
diameter: 30 mm, inner diameter: 25 mm, length: 150 mm) with aluminium foil as shock
absorber.
Weight of the target is measured precisely by a microbalance

Lu2O3 : ~10 mg
Preparation of target for encapsulation, reactor irradiation parameters
Neutron flux : ~1 × 1014 n/cm2/s

Irradiation time : 1d
Specific activity achieved and typical production yield per capsule
Specific activity : ~2 T Bqg-1Lu

Production yields : ~90% (~18 G Bq)
A 5 cm thick lead hot cell equipped with tongs, lead glass windows and apparatus inside is
used to treat the irradiated target. The apparatus consists of cutter, dissolving vessel, hotplate-
stirrer unit, reagent feeding pipe, trap for exhausted fumes, remote pipette, etc. Absolute
filters are in the exhaust line of cell.
All reagents are high pure grade and guaranteed.
125
Hydrogen peroxide
Concentration 35%, Residue on evaporation 0.05%, Heavy metals 0.0001%.
Hydrochloric acid
Concentration 35.0 ~ 37.0%, Residue on evaporation 0.001%, Heavy metals 0.000005%.
Pure water
Purified by Milli-QSP ultra pure water production system, Electric resistance >18 M:.
After irradiation, quartz ampoule is broken off carefully. Target is drawn out from it to
dissolving vessel with 2 mL 6M-HCl, then added 2 mL H2O2. The vessel is put on a hotplate-
stirrer unit and connected to trap.
The target is dissolved at room temperature (~25oC) by stirring with a magnetic rod. After
dissolution, the solution is heated and evaporated to dry.
The dried LuCl3 is dissolved in 30 mL of 1 M-HCl as product.
Target material used must be guaranteed more than 99% for radionulidic purity of the product
by activation analysis. Radioactivity of target in ampoul is measured with a calibrated well-
type ionization chamber. A small quantity of the product is spent for assay. Radionuclidic
purity is checked by gamma-spectrometry using a germanium detector system. Chemical
assay performed is the determination of acidity and heavy metal impurities.
Physical observation
Final product is colourless and clear aqueous solution. The colour of the solution and
presence of suspended particles are confirmed by an appearance test used a microscope.
Radionuclide identification
177
Lu product is checked by J ray spectrometry using HPGe detection system. Gamma
spectrum is shown in Fig. 1.
>99%.
126
127
Acidity
Acidity is determined by titration of an aliquot of product solution with 0.1 M sodium

hydroxide solution using 0.2% methyl-red solution as an indicator.
(None).
~300 M Bq mL-1
Storage conditions
The product is dispensed into glass storage bottle and stored till next production.
Disposal of waste generated
The radioactive 177mLu waste, after 177Lu has decayed, is stored.
BIBLIOGRAPHY
FIRESTONE, R.B., SHERLEY, V.S., Table of Isotopes, 8th Edition, Vol. II (1996).
128
Mercury-197 (197Hg80)
Half-life : 64.13 h
196 197
Production scheme : 80 Hg (n,J) 80 Hg
Target material : HgO powder

197
Decay product : Au
Nuclear reactions and yield:

Abundance Section 1012 n/cm2/s and properties of
of nuclide% (barns) Nuclide formed
198
1 week Saturation Hg (n,J) 199mHg
196
Hg (n,J) 197m Hg 0.15 Vm = 385 386 Half-life: 42.6 min.
IT 23.8 109±6 MBq MBq Abundance: 9.97%
93.5% h. (14.3 (14.4 V = 0.018 ± 0.04 b
mCi)/g mCi)/g
Hg Hg
196
Hg (n, J) 197gHg 0.15 Vg+m = 12.3 14.5 202
Hg (n,J) 203Hg
3080± MBq MBq Half-life: 46.61 days
180 (334.5 (396.5 Abundance: 29.86%
Vg = mCi)/g mCi)/g V = 4.9 barns.
2970 b Hg Hg
EC 100% Gamma 0.07735 18.7% IC 80.7%

197m
Hg Half-life: 23.8 Hours
IT 93.5% Gamma 0.1339 33.5% IC 85.5%

EC 6.5% 0.2790 6.1% 0.9%
Target HgO (GR/AR) 500 mg sealed in quartz ampoule.

Target purity >99.9% pure. (E. Merck/Fluka).

weld sealed.

M. Ananthakrishnan,
129
Irradiation 72 hours.
Flux 1013 n/cm2/s.
Type of facility for Standard glove box 1.5 m × 1.2 m × 1.5 m. with 5 cm lead
processing shielding with HEPA filters.
Reagents used: All the reagents used are of AR/GR grade.
Chemical processing
The irradiated can is opened and quartz ampoule broken inside a teflon tube and HgO
transferred to a 100 mL beaker. A few mL of con. HNO3 is added to it and HgO completely
dissolved. The solution is diluted with double distilled water to required volume and
transferred to a storage bottle.

226
Activity is assayed in a well type ionization chamber standardized with Ra. Radionuclide
purity is determined by gamma spectrometry using MCA.
Radiochemical form Hg (NO3)2 in HNO3 solution.
Radioactive concentration Approx. 185–370 MBq (5–10 mCi)/mL.
Radionuclide purity 203 Hg < 5%.
Specific activity >400 MBq/g Hg.
Preparation of 197Hg in elemental form for industrial applications
The irradiated can is opened and the quartz ampoule is crushed inside a tygon tube. Mercuric
oxide is transferred to a 100 mL beaker and dissolved in 30 mL concentrated HCl. The
solution is decanted into a 250 mL beaker. The dissolution vessel is washed with 20 mL
double distilled water and washings transferred to the 250 mL beaker and solution warmed on
hot plate. 10 mL solution of 10% hypophosphorous acid is added to the hot solution of HgCl2
and stirred. Reduction of HgCl2 to elemental mercury is completed in a few minutes and Hg
separates out. The supernatant liquid is separated and mercury washed with hot double
distilled water thrice. Traces of moisture from mercury are removed and beaker warmed to
dry the mercury and then transferred to a vial.
A measured quantity, 50–100 mg, of metallic mercury is taken in a vial and mercury
dissolved in minimum quantity of hot concentrated HNO3 which is then diluted with double
130
distilled water to 5 mL. Radioactive concentration of this solution is measured in a
precalibrated well type ion chamber.
Radionuclide purity is determined by gamma ray spectrometry.
Specific activity is determined by the knowledge of quantity of metallic mercury taken in the
sample for ion current measurement.
Characteristics of final product
Radioactive form Metallic mercury.
Radioactive concentration 3.7 MBq/g Hg.

197 m
Radionuclide purity Hg + 197 Hg > 95%
203
Hg < 5%.
Specific activity 3.7 MBq/Hg.
131
Mercury-203 (203Hg80)
Half- life : 46.61 d

202
Production scheme : 80 Hg (n,J) 203
80 Hg
Target material : HgO powder

203
Decay product : Tl

Abundance Section 1012 n/cm2/s And properties of
of barn One Four Satu- Nuclide formed
nuclide% week Weeks Ration
196
202
Hg (n,J) 203 29.86 4.9 410 1.5 4.1 GBq Hg (n,J) 197m Hg
80 80 Hg
MBq GBq (116.54 Half-life: 23.8 h.
(11.6 (39.97 mCi)/g Isotope abundance 0.15%
mCi)/g mCi)/g Hg V = 109 barns
Hg Hg
196
Hg (n, J) 197gHg
Half-life: 64.1 h.
Isotope abundance 0.15%
Vg+m = 3080 barns
198
Hg (n,p) 198Au
Isotope abundance 10%
199
Hg (n,p) 199Au
Isotope abundance 16.84%
E- 0.2126 100% Gamma 0.2792 81.5% IC 18.5%
Target HgO (E. Merck/JM (AR/GR) – 2 g.
Container Quartz ampoule in Standard aluminium can 22 mm dia and

44 mm ht. cold weld sealed.
Irradiation 3 months.

M. Ananthakrishnan,
132
Flux Approx. 5 to 6 × 1013 n/cm2/s.
Usual yield 4 curies after a period of one month cooling.
Type of facility for Standard glove box 1.5 m × 1.2 m × 1.5 m

processing Under negative pressure (2–3 cm WG).
Chemical process
The target is stored for one month to allow the decay of 197Hg. Can is opened and quartz
ampoule crushed in a tygon tube. HgO is transferred to a dissolution flask and 10 mL
concentrated HNO3 is added to it. The dissolution is completed by warming. The solution is
concentrated to minimum volume and diluted with required volume of 1N HNO3, filtered and
Radioactive concentration is measured in a well type ion chamber standardized with 226Ra.
Radionuclide purity is determined by gamma spectrometry. Specific activity is calculated
from the known weight of the target taken for irradiation.
Chemical form Mercuric nitrate in nitric acid solution.
Radioactive concentration 74–740 MBq/mL

197
Radionuclide purity Hg < 1%.
Radiochemical purity >99%.
Specific activity >10 GBq/g Hg.
Acidity Approx. 1 N with respect to HNO3.
Preparation of 203Hg in elemental form for industrial applications
After irradiation, the can is opened and quartz ampoule crushed in a tygon tube. HgO is
transferred to a 100 mL beaker and dissolved in 30 mL concentrated HCl. The solution is
warmed to complete the dissolution and decanted into a 250 mL beaker. The dissolution
vessel is washed with 30 mL concentrated HCl and washings added to the Hgcl2 solution. The
solution is warmed. 20 mL 10% solution of hypophosphorous acid is diluted to 50 mL with
double distilled water and is added to hot solution of Hgcl2 in HCl and stirred for a few
minutes. Mercury globules separate out. The supernatant solution is removed by decantation
and mercury washed thrice with hot double distilled water. Washings removed and trace of
moisture in the beaker containing Hg is removed. Beaker warmed to completely dry the
mercury and the active mercury transferred to a storage vial. Recovery is 98 to 100%.
133
Radioactive concentration: A known quantity 100–200 mg metallic mercury from the stock is
taken in a vial and dissolved in minimum quantity of a hot solution of concentrated HNO3.
The solution is diluted to 5 mL with double distilled water and radioactivity measured in a
well type ion chamber standardized with 226Ra.
Radionuclide purity is determined by gamma spectrometer.
Specific activity is calculated from the quantity of metallic mercury taken for assay.
Characteristics of final product
Chemical form Metallic mercury.
Radioactive concentration <200 MBq/g Hg.

197
Radionuclide purity Hg <1%.
134
Molybdenum-99 (99Mo42)
(Fission product)
Half-life : 65.94 h
235
Production scheme : U (n,f) 99Mo
99m
Decay products : Tc (t1/2 6.01 h) and 99Tc (t1/2 2.11 × 105 a)
E 1.2145 (82.4%) J 0.7395 (12.13%)

0.4366 (16.4%) 0.181 (6.0%)
0.1405 (4.52%)
0.7779 (4.26%)
Production : thermal neutron induced fission of 235U;

fission products contains 6.1 mass-% 99Mo
FIG. 1. Mo-99 process flow sheet.

W. Van Zyl de Villiers,
The South African Nuclear Energy Corporation, Ltd,
Bldg. 1900, PO Box 582,
Pretoria 0001, South Africa.
135
The targets for fission Mo-99 production consist of a uranium/aluminium alloy (containing U
enriched to 45% 235U) clad in aluminium. It contains 4.2 g 235U in one 200 mm × 45 mm
target plate manufactured by NECSA. Only very low levels of impurities that could act as
neutron poisons are allowed.
Irradiation
Irradiation is done in in-core irradiation positions in the 20 MW SAFARI-1 research reactor at

Pelindaba near Pretoria. SAFARI-1 is a tank-in-pool type light water reactor of Oak Ridge
design. Six dedicated positions are equipped with thimble tubes which allow for the insertion
and retrieval of target plates with the reactor on power. A maximum of seven target plates in
an aluminium plate holder can be irradiated per position for a period of up to 200 h,
depending on customer demand. The average thermal neutron flux is 1.5 × 1014 n/cm2/s at
20 MW. After irradiation the target plates are stored in the reactor pool for up to 24 hours to
allow for the decay in gamma heating and short-lived fission products. The 99Mo activity per
plate at the end of a 50 h–200 h irradiation varies from 200 to 500 Curies (8 × 106 – 18 ×
106 MBq).
Processing facility
A typical production line of five shielded hot cells (shielding capacity of 200–250 mm lead
equivalent) consists of the following:
– As dissolver cell containing the dissolution vessel for irradiated target plates, the first ion
exchange column, as well as waste tanks under the cell floor for the accumulation of
liquid waste for further processing after sufficient decay;
– A purification cell containing the second and third purification columns;
– A filtration cell containing the evaporator and sundry equipment for the filtration,
redissolution, sampling and bottling of the 99Mo containing solution;
– A dispensing cell containing an ionization chamber for the quantification of the product
and the dispensing thereof according to client needs; and
– A packaging cell where the product bottles are placed into transport containers, labelled
and removed for shipment to the client.
The 99Mo production hot cells are served by a dedicated ventilation system, keeping the cells
under slight negative pressure relative to the surrounding areas. It is a once-through system to
prevent any build-up of process gases. There is 100% back-up with respect to the extraction
as well as the primary filtration system, and the system is coupled to emergency diesel
generator and uninterrupted power supply standby systems.
Dedicated filtration is provided for aerosols (HEPA filters), iodine (specially impregnated
activated carbon filter beds) and noble gases. During target plate dissolution the latter gases
are trapped on activated carbon in large stainless steel columns, which are then closed off and
left for a period long enough to allow for sufficient decay of the relevant isotopes. The
dissolution rate of target plates, during which hydrogen is formed, is controlled in such a way
that the hydrogen concentration in the ventilation system is within safety limits.
Monitoring systems for noble gases, iodine, alpha and beta/gamma emitters as well as
hydrogen are distributed throughout the ventilation system for process control measures as
136
well as the quantification of releases to the environment as part of application of the ALARA
principle.
The materials and reagents used in the extraction and purification of 99Mo are prepared in a
dedicated laboratory consisting of a quarantine holding area, a section for storage of approved
materials and reagents, and a processing area where chemicals and reagents are prepared.
Raw materials received from suppliers are placed in quarantine, and released for further use
only after being tested for compliance with specified requirements. This includes analysing
raw materials for a selected constituent. Bulk reagents prepared from approved raw chemicals
are tested (where applicable) for identity and concentration. These reagents are also placed in
quarantine directly after preparation, and released only when verified to comply with
specification. Process reagents are made up and transferred to the 99Mo processing facility in
quantities just enough for each production run.
A typical specification for the concentration of process reagents is ±10%. Analytical methods
such as atomic absorption spectrometry, titrimetry and ion chromatography, with precision
and accuracy typically 1–5%, are used in the analysis of process reagents.
FIG. 2. Process scheme for Mo-99 extraction and purification.
Chemical processing
Irradiated target plates are dissolved in concentrated NaOH. A suitable oxidizing agent is
added to ensure that all molybdenum is dissolved, while at the same time leaving the non-
fissioned uranium as a solid residue for recovery at a later stage. Nuclides of only a few
elements are dissolved with molybdenum, and the purification steps following dissolution
137
have been designed to specifically ensure proper decontamination of Mo with respect to these
elements, while also giving good product recovery.
Purification is carried out by means of two anion exchange resins and one chelating resin, all
commercially available. Each purification step consists of sorption of Mo, washing to remove
any residual source solution, and elution of Mo under conditions suitable for separation from
any impurities which might still be present at the particular stage. The eluate from the third
column is filtered, evaporated to dryness, and redissolved in 0.2 M NaOH to convert the
product into sodium molybdate. Sodium hypochlorite is normally added at this stage to ensure
that Mo is maintained in the molybdate form.
Apart from the above mentioned control measures regarding process reagents, the process or
solution temperature as well as the flow rate through ion exchange columns are controlled
with predefined parameters. All actions are carried out according to prescribed checklists for
the operators.
The 99Mo product is dispensed according to clients’ requirements based on the bulk activity
measured in the fourth hot cell and the particular precalibration period. Assaying is done by
means of a frequently calibrated ionization chamber. Radioactive concentration (MBq.cm-3) is
calculated from the product activity and the final volume of product solution.
Quality control testing of the final 99Mo product is geared to provide a preliminary certificate
of compliance within 24 hours of the completion of each production run. This demonstrates
that the product is within specifications and is reported in a “less than” format. Samples from
each production run are also analysed 10 weeks after production for final certification. This
demonstrates the extent to which the product is within specifications.
Radionuclidic purity of 99Mo is determined through the following measurements in a separate

dedicated laboratory:
– J spectrometric determination of 99Mo activity by using a calibrated high purity Ge
detector;
– J spectrometric determination of 131I after separation by distillation with the aid of a
carrier and tracer;
– J spectrometric determination of 103Ru after separation by ion-exchange with the aid of a
carrier and tracer;
– E counting of 89Sr and 90Sr on a calibrated gas-flow proportional counter after separation
by ion-exchange and precipitation with the aid of a carrier;
– D spectrometric determination of the total D activity with a calibrated low background D
spectrometer after separation by ion-exchange and precipitation; and
– J spectrometric measurement of a sub-sample to identify and quantify any possible J
emitting impurities at low levels.
Radiochemical purity of 99Mo is determined by means of paper chromatography with a

mixture of hydrochloric acid, water, ether and methanol as mobile phase. The distribution of
activity on the paper is determined with a scanner, and the specific nuclide content of the
relevant areas is measured by J spectrometry.
138
Fission 99Mo, which is produced as described above, is used for the production of 99mTc
generators. The final 99Mo product complies with the following specifications, which have
been derived from European, British and United States Pharmacopoeia specifications for
Sodium Pertechnetate-99mTc:
131 99
I: Mo < 5 × 10-5
103
Ru:99Mo < 5 × 10-5
89
Sr:99Mo < 6 × 10-7
90
Sr:99Mo < 6 × 10-8
6D:99Mo < 1 × 10-9
Other 6E/J:99Mo < 1 × 10-4
>95% as molybdate (MoO4-2).
>1 Ci(3.7 × 1010 Bq)/cm3 at calibration time.
Product solvent
0.2 M NaOH, normally containing NaOCl to stabilize Mo in the molybdate form.
Calibration date
3 to 7 days after shipment to the customer.
Shelf-life
7 days after the calibration date.
Waste management
All process consumables such as pipes, ion exchange columns and reagent containers are used
for only one production run. After each run, these are collected and stored to allow for decay
of the short-lived nuclides with which it is contaminated. This is followed by compaction and
disposal as low-level waste.
Alkaline liquid waste is accumulated in shielded stainless steel tanks for later immobilization
in a cement-vermiculite mixture. Other liquid waste, which is slightly acidic, is left to decay
and is then treated with other on-site low-level liquid waste.
Hot cell off-gas is treated by adsorption and filtration as described above.
139
Being a raw material for medical end-use, it is absolutely imperative that all aspects of fission
99
Mo production are covered by a quality assurance programme. The latter should conform to
an internationally accepted code of practice for quality systems, e.g. ISO 9002, as well as
other requirements such as Good Manufacturing Practice according to 21 CFR Parts 210 and
211. Particularly important aspects are quality control of process consumables, strict control
of the chemical purification process and purity certification of the final product.
Radiological and environmental monitoring as well as thorough waste management practices

are critically important to ensure adherence to the ALARA principle and to minimize the
environmental impact of production activities.
Drug Master Files have to be submitted to the pharmaceutical regulatory authorities in the
countries where the product will be used in 99mTc generators and radiopharmaceuticals.
140
Molybdenum-99 (99Mo42)
(By neutron irradiation)
Half-life : 65.94 h
98
Production scheme : Mo (n,J) 99Mo V =0.13b
Target material : MoO3 (Fluka grade)
Target MoO3 (90–120g per batch)

Container Standard 1S aluminum cans, 22mm dia & 44mm ht cold
weldable.
Target purity >99.5%.
Enrichment nil.
Impurities Chloride, nitrate, phosphate, arsenate, silicate, sulphate to be
less than 0.0115%.
Calcium, cadmium, cobalt, chromium, copper, iron, potassium,
magnesium, manganese, sodium, to be less than 0.0195%.
Suppliers Fluka, E Merck.
Irradiation details
Reactor 100MW DHRUVA reactor.

Neutron flux 1.6 × 1014 n/cm2/s.
Duration of Irradiation 1 week.
Cooling if applicable nil.
Yield of 99Mo at EOI 1.48 GBq (40Ci) per batch.
Processing procedure
Facility: The radiochemical processing of molybdebnum-99 is carried in sealed tong boxes

kept under negative pressure (2–3 cm water gauge) and provided with 100 mm lead shielding.
The boxes are connected to high efficiency particulate air filters (HEPA) fixed at the top of
the boxes.
Procedure: Irradiated MoO3 cans are opened using specially designed can cutters and the
target is transferred to a dissolution flask containing 4N NaOH solution. The solution is
heated to 60 degrees centigrade to facilitate complete dissolution. The solution is also
simultaneously stirred by passing compressed air. The solution is then allowed to cool and
passed through a filter to remove any undissolved impurity.
Radiochemical purity Sodium molybdate in sodium hydroxide solution.

Radionuclide identification By photo peaks corresponding to 99Mo.

M. Ananthakrishnan,
141
Radioactive concentration 2.2–2.6 GBq (60–70 mCi)/mL
Radionuclide purity No other extraneous gamma emitters should be detectable in
the gamma spectrum.
Specific activity 11–15 GBq (300–400 mCi)/g.
Appearance A clear colorless solution.
Dispensing
99
Mo as sodium molybdate on sodium hydroxide solution is dispensed in 10–15 mL vials for
supply to users directly or in 100 mL vials for shipment to Radiopharmaceutical labs for use
as raw material for conversion into medical grade product for supply to hospitals for
extraction of 99Tcm.
The radioactivity is measured in a well type ionization chamber calibrated against a standard
source. The radionuclide purity is checked by taking a gamma spectrum.
142
Nickel-63 (63Ni28)
Half-life : 100 a
62 63
Production scheme : 28 Ni (n,J) 28 Ni
Target material : Ni powder (J.M. – Sp.pure)
Type of decay and energy : E(MeV) 0.066 (100%)

63
Decay product : Cu
Reaction Isotope Cross Activity of element at Secondary reactions

Abundance Section 1012 n/cm2/s And properties of
of barns 1W 1M 1 Year Nuclide formed
nuclide%
58
62
Ni (n,J) 63
Ni 3.63 14.5 670 2.7 35 Ni(n,J) 5 9Ni
28 28
KBq MBq MBq Half-life: 7.6 × 104 years
(18.3 (73.17 (0.95 Abundance: 68.08%
µCi) µCi)/g mCi)/g V = 4.6 barn
/g Ni Ni
Ni 58
Ni(n,D) 55 Fe
Half-life: 2.73 years
V = < 1 mb
62
Ni(n,D) 59 Fe
V = 0.002 mb
64
Ni(n,J) 65Ni
Abundance: 0.926%
Half-life: 2.517 h
V = 1.52 b
Target 10 g J.M.Spec Pure Ni powder.
Container 1S aluminium can 22 mm dia and 44 mm ht. cold weld

sealed.
Irradiation 8 to 12 weeks.
Flux 4 × 10 13n/cm2/s.
Type of facility Standard glove box with 5 cm local shielding. Box is

For processing maintained under negative pressure (2- 3 cm WG).

M. Ananthakrishnan,
143
Reagents
All the reagents used are of GR/AR quality and all dilutions are carried out using double
distilled water.
Chemical process
The irradiated can is opened and nickel powder transferred to a dissolution flask. 60 mL
concentrated HCl is added to it and the solution refluxed under heating for one hour to
complete the dissolution. Acidity of the solution is adjusted to 9.5 N with reference to HCl by
addition of concentrated HCl. The solution is then passed through an anion exchange column.
Dowex 1 × 8 (50 to 100 mesh) (1 cm × 15 cm) conditioned with 200 mL 9.5 N HCl. The flow
rate is maintained at 0.3 mL/minute. (The column is separately treated to recover 58Co). The
effluent is collected and concentrated to approx. 50 mL and once again the ion exchange
procedure is repeated to eliminate trace quantities of gamma emitting impurities like 58Co,
60
Co, 59Fe etc.
The effluent from the column is concentrated to minimum volume and the solution is diluted
with 0.1N HCl.
The activity assay is done by liquid scintillation counting. Radionuclide purity is controlled
by beta absorption analysis and gamma spectrometry.
Chemical form Ni Cl3 in dil. HCl solution.
Radioactive concentration 4 to 40 MBq/mL
Specific activity >200 MBq/g Ni.
144
Osmium-191 (191Os76)
Half-life : 15.4 d
190
Production scheme : Os (n,J) 191Os
Osmium-191 is used as the parent for the osmium-191/iridium-191m generator system

(Brihaye, et al., 1986a; Brihaye, et al., 1986b). The ultra short-lived iridium-191m (t1/2 4.96s)
has been used for firstpass ventriculography (Franken, P.R., et al., 1989).
FIG. 1. Production and decay scheme for osmium-191.
E 0.1424 (100%)
J 1.29.43 (29%)
1. Highly enriched and highly purified osmium-190 is generally used as the metallic powder
for production of osmium-191 to minimize any radionuclide impurities in the final
product. Depending on the desired activity yield, 10–30 mg of enriched osmium-190 are
sealed in evacuated quartz tubes.
2. Enrichments greater than 96% will provide the highest purity osmium-191.
3. Although highly enriched osmium-190 target material is used, decay of the metastable
iridum-191m in the reactor during the irradiation process forms iridium-191 which
captures a neutron with formation of low levels of iridium-192 (t1/2 73.8 days) as an
induced radionuclide impurity (Brihaye, et al., 1989; Butler, et al., 1985).
4. Highly enriched osmium-190 (>95%) is available from Isotope Distribution Office (IDO)
the Oak Ridge National Laboratory (ORNL).

F.F. Knapp, Jr., C. Brihaye,
Oak Ridge National Laboratory, Cyclotron Research Centre,
Oak Ridge, Tennessee 37830-6229, USA Sart Tilman, B-4000, Liege, Belgium
145
The calculated specific activity values for production of osmium-191 at various thermal
neutron flux values are illustrated in Fig. 2.
FIG. 2. Predicted specific activity values for reactor production of osmium-191 at various
thermal neutron flux values (from Brihaye, et al., 1989).
A highly shielded hot cell is required for processing any significant levels of osmium-191. An
apparatus similar to the one shown in Fig. 3 is required for removal of the iridium-192
impurity.
A zirconium crucible is required for the oxidative dissolution of the irradiated osmium-190
target (Brihaye, et al., 1989; Butler, et al., 1985). All other reagents and chemicals should be
analytical grade.
146
FIG. 3. Processing of reactor-irradiated osmium-191 target.
The procedure for the chemical processing of reactor-produced osmium-191 has been
described in detail earlier (Brihaye, et al., 1989; Brihaye, et al., 1986a) and is based on the
sequential oxidative dissolution of the irradiated target as summarized in Fig. 3.
The iridium-192 radionuclide impurity is always present in reactor-produced osmium-191. It

is formed by neutron capture of the iridium-191 formed via i someric decay of the metastable
iridium-191m formed by decay of osmium-191 (Fig. 1). The iridium-192 can be readily
removed by acidification of the processed solution and distillation of osmium-191 as osmium
tetroxide. The non-volatile iridium-192 remains behind in the vessel as described in detail
earlier (Brihaye, et al., 1989), and can be a source of carrier iridium-192 (Fig. 4a).
FIG. 4a. Chemical transformations used for purification of osmium-191 and removal of
iridium-192 impurity (from Brihaye, et al., 1989).
Following dissolution and distillation, the sodium perosmate solution probably has a definite
shelf-life and should be used for generator fabrication within a few days after formation,
although the effects of long-term storage on stability and decomposition have not been
evaluated and reported.
147
The required specifications for the final osmium-191 product depend upon the intended
application. For medical use for fabrication of the osmium-191/iridium-191m generators, it is
important that the iridium-192 impurity be removed. The levels of iridium-192 formed will of
course depend upon the particular reactor used for the irradiation. A gamma spectrum should
be provided to document the radionuclidic purity.
In our experience, the shelf-life of the processed osmium-191 solution may be limited.
FIG. 4b. Apparatus used for purification of osmium-191 and removal of iridium-192 impurity
(from, Brihaye, et al., 1989).
BIBLIOGRAPHY
BRIHAYE, C., BUTLER, T.A., KNAPP, F.F., JR. “The 191Os/191mIr Generator for Clinical
Use. I. Evaluation of Potential Adsorbants”, J. Radioanalyt. Nucl. Chem., 102 (1986) 399–
411.
BRIHAYE, C., BUTLER, T.A., KNAPP, F.F., JR., GUILLAUME, M., WATSON, E.E.,
STABIN, M.G., “New Osmium-191/Iridium-191m Radionuclide Generator System Using
Activated Carbon”, J. Nucl. Med., 27 (1986) 380–387.
148
BRIHAYE, C., DEWEZ, S., GUILLAUME, M., CALLAHAN, A.P., RICE, D.E.,
KNAPP, F. F., JR., “Reactor Production and Purification of Osmium-191 for Use in a New
191
Os/191mIr Radionuclide Generator System”, Appl. Radiat. Isot., 40 (1989) 183-191.
BUTLER, T.A., BUYER, C.E., KNAPP, F.F., JR., “Production of Osmium-191 in the Oak
Ridge High Flux Isotope Reactor” (Proc. International Symposium on Single-Photon Ultra-
Short Lived Radionuclides, PARAS, P., THIESSEN, J.W., Eds.), U. S. Department of
Energy, DOE Symposium Series, No. 57, Office of Scientific and Technical Information,
Oak Ridge, TN, USA (1985) 195–201.
FRANKEN, P.R., DOBBELEIR, A.A., HAM, H.R., BRIHAYE, C., GUILLAUME, M.,
KNAPP, F.F., JR., VANDEVIVIERE, J. “Clinical Usefulness of Ultrashort-Lived Iridium-
191m from a Carbon-Based Generator System for Evaluation of the Left Ventricular
Function”, J. Nucl. Med., 30 (1989) 1025–1031.
149
Osmium-194 (194Os76)
Half-life : 6.0 ± 0.2 a
E-
192
Production scheme : Os (n,J) 193Os (n,J) 194Os o 194Ir V1 = 2.0 ± 0.1 b
V2 = 38 ± 10 b
Type of decay and energy : E 2.246 MeV (85.4%)
1.918 MeV (9.3%)
1.625 MeV (1.28%)
The target material is enriched metallic osmium-192.
Because of the relatively low thermal neutron cross-sections of the osmium-192(n,J)osmium-

193 (2 barn) and for the second osmium-193(n,J)osmium-194 neutron capture (250 mb;
estimated, see Mirzadeh, et al., 1992), and the long 6-year half-life of osmium-194,
production yields are low (Fig. 1), even at high thermal neutron flux values. As an example,
2
even at a thermal neutron flux of about 2.5 × 1015 n/cm /s, a 60-day irradiation in the ORNL
HFIR provides osmium-194 is only about 18.5 MBq (0.5 mCi)/mg enriched osmium-192
(Fig. 1).
FIG. 1. Projected reactor production yields of osmium-194.

S. Mirzadeh and F. F.Knapp, Jr.,
150
An efficient method involving the thermographic conversion of the metallic osmium-192

target material to osmium tetroxide (Fig. 2) which is removed in a stream of air and
subsequently trapped as potassium osmate (Mirzadeh, et al., 1992).
FIG. 2. Apparatus for the gas-thermochromatographic system for purification of reactor-

produced osmium-194 (From Mirzadeh, et al., 1992) — 1. Metering Valve; 2. CHIMINERT
glass/Teflon connector (See exploded view); 3. Air volume flow meter; 4. Chromatographic
tube assembly; 4a. Quartz tube (2.8 cm o.d., 2.4 cm i.d., 20 cm long); 4b. Chromatographic
tube (quartz, 6 mm o.d., 12 cm long) containing 60 mesh quartz powder held in tube by quartz
wool; 5. Split tube furnace; 6. Quartz boat containing osmium target; 7. Thermocouple; 8.
Sliding ring (PVC); (c) bed support (Teflon), (d) nut (PVC), (e) bushing (PVC), (f) washer
(SS), (g) tube end fitting (PVC), (h) Teflon tubing (0.6 mm i.d.) With flanged end.
Thermochromatography separation of osmium
1. The thermochromatography apparatus is of a conventional design (Fig. 2). A quartz tube

(2 cm i.d. and 10 cm long) from one end is attached to a ball joint and the other end (the
exit end) is reduced in orifice and attached to a 4 mm i.d. chromatographic column. This
column (12 cm long) is packed with 60 mesh acid-washed quartz powder. The cold end
of the chromatographic column is attached in series to two KOH traps and one activated
carbon trap.
2. The chromatography tube assembly is placed into a split tube furnace. The boat
containing the irradiated osmium-102 sample is introduced into the tube from the ball
joint end and centered at the position of the maximum temperature at the center of the
furnace.
151
3. The furnace temperature is monitored with a thermocouple placed close to the center of
the oven and a Variac is used to control the furnace temperature. The volume flow rate of
the carrier gas (air) is monitored by a flow meter. An evolved version of the above
apparatus that is currently used for routine hot-cell operations is shown in Fig. 2.
4. For ease of remote handling connections between the chromatographic assembly and air
supply line, the traps are made with Teflon tubing (0.6 mm i.d.). The glass/Teflon-tubing
connections can conveniently be made by the use of Cheminert connectors (Valco
Instruments Co., Houston, TX). The exploded view of this connector is also shown in
Fig. 2.
5. The irradiated 192Os (50 mg or less) target is transferred to a quartz boat which is then
placed in the chromatography tube assembly. While maintaining an air flow rate of 10–
20 mL/min the furnace is turned on.
6. As OsO4 forms, it is carried by the air and trapped in 2 mL of 0.1 M KOH placed down
stream (Fig. 2). The first evidence of conversion of metallic Os to OsO4 usually occurs at
~300(C within the first 30 min of start of distillation, as indicated by the slight yellowish
color in the first trap.
7. Distillation is continued for the next 2 h where the furnace temperature is increased to
~500(C. At this point, conversion is usually complete, and the furnace is turned off. The
air flow is continued for an additional 3 h to insure quantitative transport and recovery of
the OsO4.
The gamma spectrum of the product is used to determine the purity of the distilled/trapped
osmium-194 by analysis of the 328 keV (13% abundance) gamma photon of the iridium-194
daughter after equilibrium is attained.
The final product can be stored as a solution of potassium perosmate and used for subsequent
reduction to the Os(IV) species for preparation of the activated carbon-based osmium-
194/iridium-194 generator system as described in detail for preparation of the osmium-
191/iridium-191m generator system (Brihaye, et al., 1986).
The quantitative conversion of 50 mg of Os to OsO4 within 2.5 h and under the above
conditions is demonstrated by analysis of the mass of the boat before and after distillation in
several cold runs employing natural Os metal. Consistently, a light-weight black residue (~1%
of the Os mass) remains in the boat after distillation. By spectrographic analysis, the residue
is found to be primarily graphite.
152
BIBLIOGRAPHY
BRIHAYE, C., BUTLER, T. A.,KNAPP, F.F., JR. GUILLAUME, M., WATSON, E.E.,
STABIN, M.G., “New Osmium-191/Iridium-191m Radionuclide Generator System Using
Activated Carbon”, J. Nucl. Med., 27 (1986) 380–387.
MIRZADEH, S., KNAPP, F.F., JR., CALLAHAN, A.P., Production of Tungsten-188 and
Osmium-194 in a Nuclear reactor for New Clinical Generators, Nuclear Data for Science and
Technology (QAIM, S., Ed.), Spinger Verlag Pub. (1992) 619–620.
194 194 194
MIRZADEH, S., RICE, D.E., KNAPP, F.F., JR. “Carrier-free Ir from an Os/ Ir
Generator — A New Candidate for Radioimmunotherapy,” Appl. Radiat. Isot., 43 (1992)
689–692.
153
Palladium-103 (103Pd46)
Half-life : 16.99 d
102
Production scheme : Pd (n,J) 103Pd V=3b
EC 100%
J (MeV) 0.04 (2%)
0.02 Rh X rays
IC 10%
108
Secondary reactions : Pd(n,J)109Pd (Half-life-13.46 h).
E
110
Pd(n,J)111Pd o 111Ag (Half-life-7.5days).
Target material : Palladium sponge.
Specifications and preparation target
Palladium sponge spec pure, J.M (100 mg).
Irradiation container
Standard aluminum container of dimensions: 22 mm dia × 46 mm ht and cold-welded.
Irradiation period : 4 weeks.
Neutron flux : 4 × 1013 n/cm2/s.
Yield : 370 MBq (10 mCi) (approx.).
Standard glove box of dimensions 2 × 1 × 2 m provided with lead shielding wall of 5 cm.
Chemical processing
The irradiated target palladium is allowed to cool for about a week before chemical
processing for decay of short-lived contaminants. The target is dissolved in 5 mL of aqua
regia. Excess HNO3 is destroyed by repeated treatment with small quantities of concentrated
hydrochloric acid. The solution is evaporated to small volume and 10 mL 9.5 N HCl is added
to it. Then the solution is passed through an ion-exchange column (1 cm dia × 15 cm long)
Dowe × 1 × 8, 50–100mesh conditioned with 9.5N HCl at a flow rate of 0.25 mL/minute. The
column is washed with approximately 100 mL of 9.5 N HCl. The effluent is collected for
recovery of an important by-product 111Ag.

M. Ananthakrishnan,
154
The column is washed free from HCl by passing double distilled water. Palladium is eluted
with 25 mL of concentrated ammonia solution followed by 100 mL of 1N ammonium
hydroxide. The eluate is collected and evaporated to a small volume and treated with 5 mL
concentrated HNO3. A small quantity of concentrated HCl is also added to the solution and
boiled to remove excess HNO3. The solution is diluted with 10 mL of 1N HCl.
Radioactive concentration and activity yield are calculated based on activation data such as,
period of irradiation, neutron flux and mass of the target.
This is determined by gamma ray spectrometer.
Specific activity
The quantity of palladium in the solution is estimated spectrophotometrically and the activity
is calculated from irradiation data.
Characteristics of the solution
Chemical form: PdCl3 in dilute hydrochloric acid.
Radioactive concentration: ~37 MBq (1 mCi)/mL
155
Palladium-109 (109Pd46)
Half-life : 13.7012 ± 0.0024 h

108
Production scheme : Pd (n,J) 109Pd V = 8.5 ± 0.5 b
Type of decay and energy : E- (MeV) J (MeV)

1.028 (99.9%) 0.088 (3.6%)
Palladium-109 is reactor-produced by the radiative (n,J) reaction on palladium metal targets.
Enriched high purity palladium metal targets are used. The projected production yields of
palladium-109 from irradiation of palladium-108 as a function of irradiation time at various
thermal neutron flux values are shown in Fig. 1.
FIG. 1. Calculated production yields of palladium-109 by neutron irradiation of palladium

targets as a function of irradiation time at various thermal neutron flux values.

156
An adequately shielded hot cell or other shielded facility (>3 inches of lead), for processing
the irradiated targets equipped of an off gas system is required.
Processing of palladium-109 from palladium metal targets (from ORNL radioisotopes

procedure manual, ORNL-3633, 1964)
1. Prepare equipment which includes the hot off-gas scrubber unit, 150 mL Pyrex beaker
and 100 mL product bottle.
2. Open irradiation can and transfer target into beaker under a hot off-gas scrubber
assembly.
3. Cover target material with aqua regia and heat to near boiling. Add fresh aqua regia as
required until the target material is completely dissolved.
4. Evaporate target solution to 3 to 4 mL during which time the excess acid is expelled.
5. Dilute to 50 mL with distilled H2O and transfer to product bottle. Product solution should
be clear and reddish brown in color.
Molarity of HCl
Total solids
109
Pd concentration
Radiochemical purity.
The final product should be analysed by gamma spectroscopy.
The product is supplied as the chloride in HCl solution. The radiochemical purity should be
>95%, exclusive of the silver-109m daughter activity.
The final yields of palladium-109 are usually >80%. At ORNL at a thermal neutron flux of
13 2
about 1 × 10 n/cm /s, the optimal irradiation time was about 60 hours, with an average
target mass of 50 mg, and a yield of 12.95 GBq (350 mCi).
BIBLIOGRAPHY

157
Phosphorous-32 (32P15)
Half-life : 14.26 d
32
Production scheme : 16 S (n,p) 1532 P

Abundance Section 1012 n/cm2/s. and properties of
of nuclide% barns One Four Satu- Nuclide formed
week Weeks ration
31
31
P (n,J) 32P 100 0.17 950 2.5 3.26 P (n,p) 31 Si
MBq GBq GBq Half-life: 2.62 h.
(25.6 (66 (88.2 (threshold 732 keV)
mCi)/ mCi)/g mCi)/g
g
32
S(n,p) 32 P 95.02 0.065 330 860 1.15 34
S (n,J) 35 S
MBq MBq GBq Half-life: 87.51 days
(9 (23.2 (31 Abundance=4.21
mCi)/ mCi)/g mCi)/g
g V = 0.227 b
33
S (n,p) 33P
Abundance: 0.75%
E- 1.71 MeV (Emax) 0.6949 MeV (Eav).
32
Decay product : S
Target material : Elemental sulphur (S)- redistilled.
Target Elementary sulphur (EM) GR highly purified by many cycles of

distillation purity greater than 99%, used as target for irradiation.
Container Standard 1S aluminium can (22 mm dia and 44 mm ht.) each is filled
with 18 g of sulphur. The capsules are sealed by cold welding process
and tested leak proof in boiling water. 14 capsules are normally
processed per run.

M. Ananthakrishnan,
158
Irradiation A typical irradiation of 250 g of purified sulphur at a flux of 1 × 1014
n/cm2/s. For 8 weeks produces ~100 GBq (2.5 to 3 Ci) of 32P with sp.
activity in the HE range of 185 TBq (5000 Ci)/m.mole.
Flux 1014 n/cm2/s.
Extreme care is taken in cleaning the buffed surface of irradiation container to prevent any
impurity coming in contact with the target.
Reagents
All the reagents used are of GR/AR grade.

32
P is classified as a class 3 (moderate toxicity) isotope and has an effective half-life of 14.26
days. The maximum beta energy value being 1.71 MeV. The bremsstrahlung spectrum has
maximum at 100–300 keV. The practical system of shielding 32P consists of a sheet of
perspex followed by lead. The processing plant set up in A type of radioactive laboratory
consists of a tight aluminium glove box 1.5 m × 1.2 m × 1.5 m feet size with 5 cm lead wall
on all four sides. The front and back sides of the box are fitted with 150 mm dia glove port
rings to mount gloves, gaiters, can openers, panthograph etc. A cut out 60 cm × 30 cm on
front and back side of the box is fitted with 10 mm perspex. A pair of 100 mm × 150 mm inch
× 100 mm inch lead glass on both sides provides the necessary view inside the box. Sufficient
number of glands fitted with nozzles on top as well as bottom side of box are connected to
service lines such as reagents, compressed air, suction, electric supply, cooling water etc. A
fume hood 1.2 m × 1 m × 1.5 m feet is attached to the glove box through a tunnel door of the
glove box which opens into the fume hood. An aluminium rail with a trolley runs through the
entire length of the box and ends at the tunnel box to facilitate movement of the material
inside the box. An exhaust pump connected through a HEPA filter to the plant provides the
necessary negative pressure inside the plant which is maintained at about 2 to 3 cm WG less
than atmosphere.
The process equipment consists of a distillation flask, receiver, ion exchange (cation) column,
evaporating flask and storage bottle all made of corning glass with standard joints.
Chemical process
The irradiated cans are decapped and transferred to a funnel on the distillation flask and
heated to 130 degrees C when all the sulphur melts and collects in the distillation flask. The
distillation assembly is connected to a vacuum pump and pressure reduced to 1 to 5 mm Hg.
Distillation of sulphur takes place between 180 to 200o C and is completed in 1–2 h. The
vacuum is released and flask allowed to cool. 32P activity is leached out in 100 mL 0.1 N pure
HCl heated to approx. 60–700 as H332PO4 and purified free from impurities by passing
through a cation exchange column. Dowex 50 (1 × 8). Excess HCl is removed by evaporation
under infrared lamp and then pH of product brought to 1 to 2 with respect to HCL.
The distilled sulphur collected in a receiver is found suitable for reuse as target after a period
of six months.
159
The stock solution is assayed for radioactivity in ion chamber by measuring the ion current
produced by bremsstrahlung radiation (or by E- counting in a GM counter). Specific activity is
determined by spectrophotometric method measuring the absorption maxima at 660 nm of the
malachite green molybdophosphate complex containing 32P.
The radionuclide purity is determined by finding the range of beta by beta absorption using
GM Counter and absence of any gamma emitting impurities in gamma spectrum (MCA).
Radiochemical purity is determined by paper chromatography using a solvent mixture
consisting of isopropanol, ammonia and trichloroacetic acid.
Rf of orthophosphate 0.76
Rf of metaphosphate 0.00
Rf of pyrophosphate 0.40.
Radiochemical form H3PO4 in dilute HCl.
Radioactive concentration 1.11 to 2.96 GBq (30–80 mCi)/mL.
Radiochemical purity Orthophosphate content >95 per cent.
Radionuclide purity >99%, no extraneous gamma emitting impurities

noticeable.
Specific activity >110 TBq (3000 Ci)/mM of P (>111 TBq).
Appearance A clear colourless solution turns the colour of container

glass vial brown.
Intended use H3 32PO4 is used in the preparation of 32P labelled

nucleotides. It is also used for bone pain palliation in
metastasis. Phosphatic fertilizers with labelled 32P are
prepared using H332PO4.
160
Phosphorus-32 (32P15)
32
Production scheme : S (n,p) 32P
Sublimated sulphur in the form of fine powder is used as a target material. It is obtained by
evaporation and sublimation condensation of sulphur in the inert gas atmosphere.
Trade name: Sulphur sublimated for analysis Chemical specification:
assay of sulphur >99.96%
sulphated ash <0.02%
arsenic absence
water <0.10%
acids (as H2SO4) <0.005%
organic matter <0.015%
solubility in NaOH complete
Supplier: Research and Development Centre of Sulphur Industry (“SIARKOPOL”), 39–405

Tarnobrzeg, Poland.
Sulphur is melted and poured to the aluminium capsules which are immersed in the cooling
water bath. After cooling down the capsules are sealed and transferred to the irradiation site.
Irradiation parameters, specific activity and total yield
Irradiation site: MARIA reactor SM-3 reactor

IEA, Swierk, Poland NIIAR Dymitrovgrad,
Russia
Assembly: vertical irradiation channel in aluminium block
Capsules: aluminium, I 15, length 88 mm aluminium, I 8, length 80
mm
Sealing: cold rolling welding
Mass of target: about 19 g about 3 g
14 2
Reactor flux: 10 n/cm /s 1.37 × 1014 n/cm2/s
Irradiation time: 5–6 cycles of 100 hours 20 days
The average activity obtained (calculated at the activation end) is about 8.15 GBq (220 mCi)
32
P/g of sulphur.
The hot cell of 100 mm lead wall equipped with manipulators and connected to the separate
ventilation system. Filters on the air outlet: paper-charcoal. Standard under pressure inside the
hot-cell is 20 mm H2O.

K. Chrustowski
Radioisotope Centre, OTWOCK
Swierk, POLATOM, Poland.
161
Sulphuric acid 96% : Ultrapur, supplier Merck.

Ethyl alcohol 96% : pure for analysis, supplier: Polish Chemicals.
Hydrochloric acid 36% : reagent Ph.Eur., supplier Merck.
Purified water : deionized water, Elix 10 system, Millipore.
The irradiated target material is melted and poured into water. Dispersed material is dried out
and grind to the fine powder. The leaching process is carried out in diluted sulphuric acid
solution with addition of ethyl alcohol and continuous agitation. Phosphorus-32 is separated
from the residual sulphur by filtration. The obtained solution is evaporated to about 5 mL
volume, transferred to the glass vial and autoclaved for about 1h at 131oC. The obtained
product solution is purified by chromatography. First on the column filled with Dowex 50W ×
4 (cation exchanger) eluted with water and then on the column with cellulose DE-11 (anion
exchanger) eluted with 0.01 M HCl. The obtained solution of H332PO4 is diluted with 0.01 M
HCl to the desired activity. Schematic diagram of the production process is presented on the
next page.
Parameters of the obtained solution are controlled: pH, radiochemical purity, specific activity,
radioactive concentration and radionuclidic purity.
Natural sulphur consists mostly of 32S but it contains also other isotopes of sulphur like 33S,
34
S and 36S. Due to possible reactions: 33S (n, p) 33P and 34S (n, J) 35S phosphorus-33 and
sulfur-35 can be present in the product.
33
P has a half-life of 25,3 days and decays by E- with the energy of 250 keV.
35
S has a half-life of 87,5 days and decays by E- with the energy of 167 keV.
Test for radionuclidic purity
Gamma radiation impurities
The measurement is performed by gamma-spectrometry (HPGe detector with the volume of

70 cm3 and resolution of 0.8 keV at 122 keV from 57Co and 1.8 keV at 1332 keV from 60Co).
The spectrum is recorded by multichannel analyser ND-76 (The Nuclear Data, Inc.) 1 mL of
the solution in a standard glass vial is measured. J-radionuclidic impurities are detected at the
lowest limit of 5 × 10-5%. In most of the produced batches J impurities were not exceeding
0.001%.
Beta radiation impurities
The measurement is performed on anthracene crystal detector (I 15 × 8 mm) and spectrum is

recorded by multichannel analyser ND-76 (The Nuclear Data Inc.). The sample is prepared in
the form of point source on mylar foil. In most of the produced batches the results of 35S
determination in the product were far below 0.1%
162
Test for radiochemical purity
The impurities in the form of pyrophosphate and polyphosphate are removed from the product
at the chromatographic purification step. The efficacy of this process is controlled by paper
chromatography (radiochemical purity control) in the system presented below:
Whatman 1 and the mixture of isopropyl alcohol: water: 50% trichloracetic acid: 25%
NH4OH (75:15:10:0.3 v.v.) as a mobile phase, developing time: 12–17 h.
At the starting point of the paper strip the drop of carrier mixture is placed prior to analysis
which contains in 5 µl of solution phosphorus in the form of: orthophosphate — 5 µg
pyrophosphate — 10 µg
metaphosphate — 10 µg
At these conditions the phosphoric acid, H332PO4 migrates with a solvent (Rf = 0.64–0.67)
Radiochemical impurities: in the form of pyrophosphate migrate to the Rf = 0.35–0.38
in the form of polyphosphate migrate to the Rf = 0.0–0.22.
Test for radioactive concentration
Activity of the known volume of the solution is measured in 4S ionization chamber (the
overall uncertainty of the measurement ± 3%) which was previously calibrated using 32P
standard source.
Test for specific activity
The content of phosphorus in the solution is determined by spectrophotometric method. In the

acidic media phosphoric molybdate complex is formed which maximum absorbance can be
measured at O = 620 nm.
Description of the method
Reagent A: prepare the mixture of one volume of 4.2% ammonium molybdate in HCl with
three volumes of 0.0045% malachite green and stir well for about 20min.
Blank: 20 µl of 0.01N HCl, 60 µl of 1.33M HCl and 320 µl of reagent A.
Test solution : 20 µl of H332PO4 solution, 60 µl of 1.33 M HCl and 320 µl of reagent A.
Each solution is mixed gently and its absorbance measured against blank at l = 620 nm.
The content of H332PO4 is read of the calibration curve.
Specific activity, rs of the H332PO4 solution is determined on the basis of its radioactive
concentration according to the formula:
C
rs = R
CP
where: CR — radioactive concentration of the solution [GBq/mL]
CP — concentration of phosphorus in the solution [ngP/mL]
The specific activity (theoretical) of the carrier free H332PO4 solution is over 9 TBq/mL.
Test for chemical purity
Chemical impurities in the H332PO4 solution are determined by DC spectrography. This

method is not applicable to sulphur determination. The drop of the solution is placed on the
graphite electrode, evaporated to dryness and the dry residuum is excited in the electric spark.
163
Intensities of the emitted lines in the recorded spectrum are evaluated. The limits for
impurities in 32P- solution are as follows:
Element Concentration Element Concentration Element Concentration

[µg/mL] [µg/mL] [ µg/mL]
Fe 0.2 As 0.5 Cd. 0.3
Cu 0.1 Al. 0.5 Si 0.2
Ca 0.1 Ba 0.1 Mg 0.2
Pb 0.2 B 0.2 Mn 0.1
Te 0.5 Zn 0.5 Ni 0.1
Test for pH
Potentiometric pH determination of the radioactive H332PO4 with a glass electrode immersed

in the solution is not possible. Therefore pH of the solution is determined by colorimetric
relative method (paper strips). The strips are covering the pH range specified for the H332PO4
Sensitivity of the strips is controlled periodically.
TESTS SPECIFICATIONS
Identification:
beta -spectrum absorption curve of maximum energy 1.71MeV
Characters Clear, colourless liquid
pH 1.0–2.2
Radionuclidic purity >99.5%
Radiochemical purity >99.0%
Radioactive concentration t 14.8 GBq/mL
Specific activity t 9 TBq/mg P.
Chemical purity t 99.9%
32
P in the form of ortho-phosphoric acid is used for production of nucleotides labeled with 32P
etc. and for production of radiopharmaceutical: Sodium ortho-phosphate -32P for injection,
destined for therapy of polycythemia vera and polythrombocythemia.
Shelf-life: four weeks from the calibration date.
Disposal of generated waste: The residual sulphur which still contains some not leached
phosphorus-32 is melted and poured to the metal containers and then disposed as a solid
waste.
Preparation and cleanup of the facility and preparation for processing of next
production batch: The processing is performed in single steps which are performed in the
destined cells of a hot cell. Therefore there aren’t any special requirements for cleanup of the
facility. Glass vials for final product dispensing are washed and heated in 250oC prior to use
and closures are washed and autoclaved.
164
The glass beakers and other vials used during processing of carrier-free 32P must be made of
good quality glass (high hydrolytic resistance). This prevents washing out of cations which
may contaminate the product and reduces adsorbance of carrier-free phosphorus-32 on glass
walls which may influence the yield of the process.
Preparation of target material in the form of melt and then melting of residual sulphur for
waste disposal make the handling of sulphur easier, its volume is reduced and contamination
of laboratory space and inside a hot-cell is avoided.
FIG. 1 Beta spectrum of P-32 on the antrancene detector.
FIG. 2. Gamma spectrum of P-32 on HPGe detector.
165
BIBLIOGRAPHY
NOWAK, K., PANASIEWICZ, J., DOMARADZKI, M., Production of ortophosphoric acid

H332PO4 of chromatographic purity, Patent No. 289923 (1993).
166
Phosphorus-33 (33P15)
Half-life : 25.3± 0.12 d

36
Production scheme : Cl (n,D) 33P V = 0.59 mb
33
S (n,p) 33P V = 1.6 mb
Type of decay and energy : E 0.2485 MeV (max)
Phosphorus-33 is a useful radioisotope for medical research and has a longer half-life and less
energetic beta emission than phosphorus-32. Phosphorus-33 had been routinely produced at
the Oak Ridge National Laboratory (ORNL) by the (n,D) reaction by neutron irradiation of
chlorine-36-enriched potassium chloride targets (Brown, et al.; Nuclear Medicine Group
Procedure #2). Phosphorus-33 can also be produced by the enriched sulfur-
33(n,p)phosphorus-33 reaction, since the natural abundance is only about 0.75%. (Lewis, et
al., 1965; Lewis, et al., 1967).
The target material for the (n,D) route is chlorine-36-enriched potassium chloride and
enriched sulfur-33 for the (n,p) route.

36 36
As an example of production yields, 66 day irradiation of 3 grams of K Cl (60% Cl) in the
ORNL High Flux Isotope Reactor (HFIR) provided 2 Curies of phosphorus-33 after
33
processing. Using the (n,p) route, irradiation of 275 mg of enriched S (68%) in the CP-5
Reactor at the Argonne National Laboratory (ANL) at Ith = 2.66 × 1013 n/cm2/s for 23 days,
32
gave a phosphorus-33 yield of 90 MBq (2.44 mCi) at reactor discharge (7.7 )Ci of P
impurity). At the Missouri University Research Reactor (MURR) irradiation of recycled
14
enriched sulfur-33 (From Russian source) for 69 days at Ith = 3 × 10 n/cm2/s gave a yield of
74 GBq (2 Ci)/2 g.
An adequately shielded hot cell is required for opening the irradiated reactor target but the
phosphorus-33 can be processed in a glove box or fume hood with adequate shielding.
The following procedure has been tested and proven satisfactory for the preparation of
carrier-free products of 33P in the form H333PO4. Phosphorus-33 is produced by neutron
irradiation of K36Cl (~60% 36CL) sealed in quartz ampuls which are in turn sealed in
aluminum RB tubes for insertion in the High Flux Isotope Reactor (HFIR). The nuclear

167
reaction is 36Cl(n,D)33P. A typical target containing 3.0 grams of K36Cl will yield ~74 GBq
(2000 mCi) of 33P product after a 66-day irradiation period.
The processing of the irradiated enriched chlorine-36 targets and recovery of the chlorine-
36-enriched target material are described below
1. In the hot cell, open the target unit over a plastic tray and remove the quartz ampoules.
Insert the quartz ampoules in the plastic break-tube, stopper the end, and crush the
ampoules.
2. Transfer the contents of the break-tube to a 150 mL beaker, rinse the break-tube with
pure water and transfer rinses to the 150 mL beaker. Stir the solution to dissolve the KCl
and then decant the solution to the 500 mL product bottle.
3. Continue additions of pure water to the 150 mL beaker containing the broken quartz
followed by stirring and decantations to the 500 mL product bottle until ~ 300 mL of
solution has been accumulated.
4. Cap the 500 mL product and transfer to the glove box. Proceed with glove-box operations
within 3 hours or less.
The following procedure can be conducted in a glove box
1. Filter the hot-cell product solution through a medium-frit glass filter using vacuum and
wash the filter with pure water and discard the filter
2. Transfer the K36Cl solution to a 500 mL beaker. Rinse the suction flask with pure water
and add rinses to the beaker.
3. Add the 150 mg of Fe2(SO4)3 solution to the beaker and adjust the solution pH to ~10
with NH4OH.
4. Heat the solution to ~80(C to form a flocculent brick-red precipitate which carries the
33
P activity. Cool to ambient temperature.
5. Filter the slurry through a medium-frit glass filter using a suction flask. Rinse beaker with
pure water containing a few drops of 1 M NH4OH and add to the filter. Let filter pull dry
and read at 6–8 inches with a Cutie Pie inserted in the glove port. Reading should be ~10
R/h directly above the filter cake.
6. Transfer the filtrate and washings, which contain the valuable K36Cl target material to a
clean bottle, cap, and save for subsequent recovery operations.
7. Break vacuum on suction flask. Add ~20 mL of 1 M HCl to the filter funnel and allow to
stand until the Fe(OH)3 dissolves. Add vacuum and pull the solution into the suction
flask. Check to make sure all of the precipitate dissolved, if not repeat the
8. HCl addition. Otherwise, wash the filter thoroughly with pure water.
9. Transfer the filtrate to a beaker, wash suction flask with pure water and add washings to
the beaker.
168
10. Adjust the pH to ~10 with 1 M NH4OH, heat to ~80(C and cool to ambient temperature
to reform the Fe(OH)3 precipitate and carry the 33P recovery has been obtained.
11. Repeat steps 7, 8, and 9 three more times using clean glassware each time. The filtrates
from the Fe(OH)3 precipitations are accumulated and held until it has been determined
that a satisfactory 33P recovery has been obtained.
12. Dissolve the final Fe(OH)3 precipitate in 6 M HCl, rinse filter with 6 M HCl. Hold total
volume of 6 M HCl to 25 mL or less. Note: Further processing can be deferred until the
next day if desired.
Extraction of Fe3+ from 33P solution
1. Transfer 6 M HCl solution from II, 11 to a 100 mL separatory funnel along with 6 M HCl
rinses of the vessel.
2. Add an equal volume of methylisobutyl ketone (MIBK) and shake for 2 minutes. Let
phases separate completely.
3. Drain the acid phase (lower) into the second 100 mL separator funnel and ~0.5 mL of the
organic phase (upper). Add an equal volume of MIBK, shake 2 minutes, and let phases
separate completely.
4. Drain almost all of the acid phase (lower) into a 150 mL beaker. Leave ~0.5 mL of the
acid phase in the separator funnel. Dilute out the small acid heel by addition of three
1 mL portions of 6 M HCl with draining of ~1 mL after each addition. Do not shake the
separator funnel and do not let any organic phase enter the beaker.
5. Evaporate the 6 M HCl solution to a damp-dry solid using a hood and NaOH scrubber
solution to trap the HCl vapor.
6. Dissolve the solids in ~5 mL of 0.01 M HCl and pass through a clean AG-50W-X8
column and catch effluent in a 150 mL beaker. Wash original beaker with pure water and
pass through the ion-exchange column. Wash column with ~15 mL of pure water.
7. Evaporate the solution to damp-dryness and dissolve the solids in 25 mL of 1 M HCl.
8. Pass the solution through a Millipore-Millex (0.22 µ) filter into a labeled, 100 mL product
bottle.
9. Remove ~2 mL of the solution for local assay of 33P and 32P concentration and submit a
sample for complete assay.
The isolation of carrier-free phosphorus-33 from neutron irradiated enriched sulfur-33

targets is, as follows:
Solvent extraction method
1. Following irradiation the sulfur target is dissolved in dichloroethylene and the

phosphorus extracted with an equal volume of 1.0M HCl. By gently heating the solution
169
to reflux temperature, the rate of extraction is accelerated and more complete during
33 33
which the P2O5 is converted to H3 PO4.
2. The enriched sulfur-33 target material is recovered by simple evaporation of the

dichloroethylene solution following extraction of the phosphorus.
Distillation method
o
1. The irradiation enriched sulfur-33 target is heated at 450–475 C and the distilled sulfur
recovered.
o
2. The residue containing the phosphorus-33 as P2O5 is leached with 1 M HCl at 80 C.
33
3. The solution is heated at for 4 hours for conversion to H3 PO4.
The relative phosphorus-33/phosphorus-32 content is determined by beta liquid scintillation

counting. From an aliquot of the acidic phosphorus solution, phosphomolybdic acid is
extracted with n-butanol and the sulfur-35 content of the aqueous solution is analysed by
liquid scintillation counting. The sulfur-35 levels are usually <0.5% and not other
radiocontaminates are usually detected.
Both methods work well for the reactor production of phosphorus-33 but the enriched sulfur-
33 target material for the (n,p) reaction is more widely available.
BIBLIOGRAPHY
BROWN, L., CALLAHAN, A.P., Taken from ORNL Nuclear Medicine Program Procedure
#2, Phosphorus-33 Processing Procedure, ORNL, Tennessee (1979).
LEWIS, R.E., REYNOLDS, S.A., Preparation of Phosphorus-33 by Irradiation of Enriched
Sulfur-33 in Highly Thermalized Flux, Isotopes Development Center, Oak Ridge National
Laboratory (1967).
LEWIS, R.E., BUTLER, T.A., Reactor Neutron Cross-Sections for Production of
Phosphorus-33 from Clhorine-36 and Enriched Sulfur-33 in the Oak Ridge Research reactor,
Isotope Development Center, Oak Ridge National Laboratory (1967).
170
Platinum-195m (195mPt78)
Half-life : 4.02 ± 0.01 d

194
Production scheme : Pt (n,J) 195mPt
Type of decay and energy : J (MeV) 0.12979 (2.83%)

0.1295 (0.084%)
0.0989 (11.4%)
0.03089 (2.28%)
Target material : 95% enriched 194Pt (metal) from ORNL

or ISOTEC Inc., and 95.54% enriched 194Pt (metal)
from ICON, USA
Flow chart of procedure
See Fig. 1.
1. Reactor used and which assembly: KUR (Kyoto Univesity Reactor) and Hydraulic Tube
(Fig. 2).
2. Capsule details as per Fig. 3, weight 69.5 g made of Al. Silica tube: 1.8 g.
3. Mass of target per capsule: 10–100 mg.
4. Preparation of target for encapsulation, reactor irradiation parameters: 194Pt-metal powder
is packed into a silica tube and sealed at 1 × 10-5 mm Hg pressure. The sample is
irradiated at a flux of 8.15 × 10-13 n/cm2/s for a period of 75 hours.
5. Specific activity achieved and typical production yield per capsule: Sp. Act.
11.1 MBq/mg-Pt and Prod. Yield: 111–1110 MBq/capsule.
6. Properties of various 195mPt-compounds are given in Table 1.
TABLE 1. CHEMICAL AND PHYSICAL PROPERTIES OF VARIOUS Pt-COMPOUNDS

SYNTHESIZED
CDDP TDDP DWA2114R CBDCA

Chemical yield (%) 61.0 62.3 65.5 59.1
Chemical purity (%) 99.7 98.5 99.2 99.3
Radionuclidic purity (%) c.a. 100 100 100 100
Specific activity (MBq/mg) 7.4 7.4 5.0 6.7

Mitsuhiko Akaboshi,
Research Reactor Institute, Kyoto University, Japan.
171
FIG. 1. Synthesis route map of various 195mPt-labelled compounds.
172
FIG. 2. Capsule handling station.
FIG. 3. Irradiation capsule.
173
See Fig. 4 indicating intermediate and final product.
FIG. 4. Platinum-195m compounds.
From right 1. Irradiated sample (Pt) dissolved in aqua regia.

2. after evaporation the sample (Pt(IV)) was dissolved in H2O.
3. The sample (Pt(II)) after reduction with hydrazine.
4. Product (195mPt-CDDP) after reaction with NH4OH and evaporated.
195m
5. Pt-CDDP dissolved in physiological saline.
As the final concentration, in the case of CDDP, is higher than 1 mg/mL in physiological
saline, a long time (overnight) storage in a refrigerator makes the CDDP precipitate.

195m
An HPLC Unit along with an Automatic synthesizer is used in synthesize of various Pt
compounds and the same is shown in Fig. 5.
The gamma spectrum of the irradiated 194Pt target and synthesized finished product 195mPt-
CDDP is taken to ensure the purity of the product. Figs. 6 and 7 shows the gamma spectra
obtained. Figs. 8 and 9 indicate the results of HPLC analysis carried out on labeled CDDP and
chromatogram on the CDDP fraction.
174
FIG. 5. Automatic synthesizer and HPLC-apparatus inside a hot-cell.
FIG. 6. J ray spectrum of irradiated 95% enriched 194Pt.
175
FIG. 7. J ray spectrum of 195mPt labeled CDDP.
FIG. 8. HPLC analysis of 195mPt labeled CDDP (Sample: 20 µl specimen taken out at the final
step of the synthesis; Elution: H2O, at 4.0 mL/min).
176
FIG. 9. Re-chromatogram of the CDDP fraction (from Fig. 8).
BIBLIOGRAPHY
AKABOSHI, M. et. al., Annu. Rep. Res. Reactor Inst. Kyoto Univ., 23 (1990) 64–69.
– Int. J. Radiat. Biol., 66 (1994) 215–220.
– J. Radioanal. Nucl. Chem, 217 (1997) 179–183.
– J. Radioanal. Nucl. Chem., 236 (1998) 145–148.
– Jpn. J. Cancer Res., 83 (1992) 522–526.
– Jpn. J. Cancer Res., 87 (1996) 178–183.
– Jpn. J. Cancer Res., 88 (1997) 506–511.
– Nucl. Med. Biol., 20 (1993) 389–393.
– Nucl. Med. Biol., 21 (1994) 953-958.
– Toxicol. Environ. Chem., 38 (1993) 51–60.
– Jpn. J. Cancer Res., 85 (1994) 106–111.
AKABOSHI, M., et. al., Annu. Rep. Res. Reactor Inst. Kyoto Univ., 20 (1987) 150–154.
EHDICH, W., et. al., Annu. Rep.Res. Reactor Inst. KyotoUniv., 22 (1989) 97–101.
177
KATAOKA, M., et. al., Radiat. Med, 11 (1993) 247–250.
– Radiat. Med., 11 (1993) 173–176.
KAWAI, K. et al., J. Radioanal. Nucl. Chem Letters, 136 (1989) 67–74.

– Annu. Rep. Res. Reactor Inst. Kyoto Univ., 19 (1986) 42–47.
– Annu. Rep. Res. Reactor Inst. Kyoto Univ., 25 (1992) 78–82.
– J. Labelled Compd. Pharmaceut., 36 (1994) 65–71.
– J. Radioanal. Nucl. Chem. Letters, 164 (1992) 123–130.
– J. Radioanal.Nucl. Chem. Letters, 199 (1995) 207–215.
MIYAHARA, T., et. al., Japan J. Cancer Res., 84 (1993) 336–340.
178
Rhenium-186 (186Re75)
185
Production scheme : Re (n,J)186Re V = 112 b
Type of decay and energy : EC o 186W; E- o 186Os
Decay Scheme
The 137 keV J-ray energy (9.42%) provides an excellent tool for calibration and activity
measurement.
Operations and procedures flow chart
1. Target preparation 7. Total volume/activity-calibration

1–12 mg metal; 185Re >94% weighing/ionization chamber
2. Irradiation-HFR 8. Dilution/filtration
5–10 days 0.9% NaCl/0.22 µm filter
3. Target dissolution 9. Final calibration
200 µl 30% H2O2; 40ºC; 25 min. Radioactive concentration
4. H2O2 evaporation-low press. 10. Dispensing/assay 186Re
150–250 Pa; 40ºC; 70 min.
5. Residue dissolution 11. Quality control
isoton. saline-6 mL certificate
6. 0.22 µm filtration/collection 12. Packaging/shipment
186
Re-NaReO4-concentrate-6 mL ART 64 h. AEI
Material: Re-powder, metal Isotopic composition: 185Re 187Re

Isotopic enrichment: min. 94% 185Re Supplier: US-DOE or: Campro-Scientific
Total metallic impurities: d0.1% Manufacturer: ORNL-Tennessee

H. Panek Finda,
Mallinckrodt Medical B.V.,
Weserduinweg-3,
NL-1755 LF Petten, Netherlands.
179
Irradiation parameters, specific activity, total yield at EOI
Reactor: HFR-Petten (NL) operated by JRC Eur. Comm. in operation since 1962.
Type – pressurized tank-in – pool, light water-cooled and moderated, operated at 45 MW.
Facility – TIRO: Thermal Flux Irradiation Device for Radioisotope Production in-core
reloadable during reactor cycle
Capsule: Desiccator-dried target material 1–12 mg is encapsulated under N2 in clean and
depyrogenated synthetic quartz-“Spectrosil”-ampoule I.D. 9.3mm, max L=55 mm.
Irradiation: Time: 240 h.; Flux: 2.2–3 × 1014n/cm²/s
EO1 yield: 65–88 GBq (1750–2390 mCi)/mg for 97.4% 185Re enrichment
Typical spec. activity EOI: 68 GBq (1840 mCi)/mg
Processing facility
Standard hot cell provided with 1 activated charcoal and 1 absolute filter in the exhaust-
line. Required: negative pressure 150–250 Pa; max. dose/rate 1 µSv/h at 1m distance from the
cell.
Analysis of raw material, reagents and chemicals required for processing
Target material 185Re-metal : isotopic composition and 185Re enrichment-ICP/MS min.

94% metallic impurities-ICP/MS max. 0.1%.
30% H2O2 anal. Grade : Pharmacopoeia Eur.
0.9% NaCl for injections : Pharmacopoeia Eur.
The irradiated ampoule is removed from the aluminium can, behind the shield of a hot
cell. The ampoule is then properly cleaned by sonication in Re-processing cell. The tip of the
ampoule is removed by means of electrical ampoule opener (2) and the ampoule is transferred
into a glass ampoule holder (1). After addition of magnetic mini-bar into the ampoule, the
holder is crimp-sealed and positioned on second production panel where a required micro-
volume of 30% H2O2 (e.g. 200 µl/ 4 mg target) is added. After 5 minutes on still-standing, the
ampoule holder is locked in the miniature low pressure distillation apparatus (3) provided
with off-gas trap (4) and hot-water jacket (5). Re is then completely dissolved under constant
stirring at elevated temperature (+ 40°C; 20 min.). The excess of H2O2 is removed from
residing HReO4 by means of low pressure distillation (–40 kPa; +40ºC; 70 min.).
Any escape of vapours to the pump is prevented by incorporation of a system of 2 Re-
traps and 2 moisture traps in the vacuum exhaustion line. The dry Re-residue (6) is dissolved
in portions of isotonic saline (7) and quantitatively transferred via 0.2 µm filter into a sterile
crimp-sealed collection vial (8) on the 3rd production panel. All operation steps in this
validated process are computer controlled and all additions of solutions are conducted by
means of the electronic pipette system. The vial, containing 6 mL of (186Re)-NaReO4-
Concentrate is transferred into a dedicated hot cell system in the Radiopharmacy, where after
the volume/activity calibration in well-type ionization chamber and weighing on electronic
balance, the concentrate is diluted to required radioactive concentration (0.9% NaCl) by
means of positive N2-pressure. The finally calibrated solution is dispensed into the transport
vials where each of the vials is again assayed for total vial activity prior to packaging and
shipment.
180
FIG.1. In cell equipment for Re186 processing
The final product is dispensed according to the internationally recognized method, where
the nominal value of the dispensed activity lies between 90–110%. All vials are assayed in
well-type, standard-calibrated ionization chamber where the ionization current is corrected for
present 188Re-impurity and the vial geometry at the time of measurement. Radionuclidic
purity is determined by means of Ge-detector combined with multichannel analyser and
computer system where all J-energies originated from other radionuclides than 186Re are
subtracted and computed as radionuclidic impurities. 188Re impurity is individually
determined and evaluated in relationship to 186Re activity.
Description: clear, aqueous, slightly yellow-orange solution, free of visible impurities,

contained in labelled 10-mL moulded vial
Chem. composition per mL of Final Solution: approx. 0.4 mg NaReO4; 9.0 mg NaCl
pH: 2.5–5.0
Radiochem. Purity: t98% as ReO4- [PC (Whatman 3MM; 20–25ºC; 15 cm;
25 g Na2 HEDP/100 mL 0.9% NaCl; RF 0–0.25 hydrolysed, reduced Re)]
Radioact. concentration: =8,5 GBq/mL at ART (=230 mCi/mL)
H2O2: d5 µg /mL [Merckoquant 10011]
Specific activity: =29.6 GBq/mg Re at ART (=800 mCi/mg) – [ICP/AES and ionization
chamber]
Radionuclid. purity: 99.9% [Ge-detector]
188
Re assay: max. 6.2 kBq/MBq 186Re [Ge-detector]
Comments
1. Activity reference time (ART) is on Wednesday 8.00 CET (max. 56 h after EOI).
2. (186Re) NaReO4 Radiochemical is not a sterile solution – therefore it is supplied as: not
for direct human application.
3. The product can be used for preparation of sterilized pharmaceuticals and for research.
4. The radioactive waste generated during processing and Q.C., can be handled as a short
half-life radioactive waste.
5. All glassware and small accessories that come in contact with the product, such as:
needles and tubing used for transfer of fluids are disposed after every production run.
181
– Target material is hygroscopic – should be protected from moisture.

– To prevent violent reaction during dissolution, the 1st five minutes of contact with 30%
H2O2 should be motionless.
– All free H2O2 in dissolved target solution must be evaporated. Presence of H2O2 in
perrhenate can be detrimental to all labelling reactions – based on reduction of ReO4- to
lower oxidation state.
– High specific activity and chemical purity are essential for labelling of monoclonal
antibodies and peptides [3].
– High radionuclidic purity is essential for human applications.
– Relative proportion of 188Re-impurity to 186Re is dependent on irradiation time. Longer
irradiated (e.g. 5 days or more) results in lower 188Re-impurity.
BIBLIOGRAPHY
COURSEY, B.M., et al., The Standardization and Decay Scheme of Rhenium-186Re,

Appl. Radiat. Isot. Vol. 42, No. 9 (1991) 865–869.
GOLDENBERG, D.M., GRIFFITHS, G.L., Radioimmunotherapy: arming the missiles. J.
Nucl. Med. Vol. 33, (1992) 1110–1112.
KARLSRUHER NUKLIDKARTE 6, Auflage (1995).
182
185
Production scheme : Re (n,J) 186Re
Rhenium-186 is of broad interest for the preparation of a variety of rhenium-186-labeled

therapeutic agents for applications in nuclear medicine and oncology (Knapp, et al., 1999),
and is produced in a nuclear reactor by the neutron irradiation of enriched rhenium-
185 targets (Figure 1). An alternate accelerator route is by proton or deuteron irradiation of
186 186
enriched tungsten-186 targets via the W(p,n) Re (Shigetha, et al., 1996) and
186 186
W(d,2n) Re reactions, respectively (Szelecsenyi, et al., 1999).
Although the reactor route can produce relatively high specific activity rhenium-186 even
at low to moderate thermal neutron flux values, for many applications, such as for the
radiolabeling of peptides and antibodies where receptors are present at very low
concentrations and can be easily saturated, requires the availability of a very high thermal
neutron flux or production of carrier-free rhenium-186 in an accelerator.
Highly enriched rhenium-185 (>99%) targets are required for reactor production.
The projected specific activity of rhenium-186 as a function of irradiation time for

various thermal neutron flux values is shown in Fig. 1.
FIG. 1. Projected production yields of rhenium-186 at various thermal neutron flux values.

A.L. Beets and F.F. Knapp, Jr.,
183
The chemical processing of reactor-irradiated enriched rhenium-185 targets is the same

as described for the production of rhenium-188 by neutron irradiation of enriched rhenium-
187 targets:
1. The target (i.e. aluminum and/or quartz tube) is opened and if a quartz tube is used, the
tube containing the irradiated rhenium-187 target material is carefully opened with a
break tube or cut open, etc. The target material and crushed quartz glass are transferred
into a conical 3–5 mL Pierce processing vessel placed in a heating block. About 2 mL of
30% hydrogen peroxide solution is then added.
2. The processing vessel is sealed with a Teflon-lined cap. For processing at ORNL, a
sidearm attachment (evaporation head) is also used and vented through a coarse charcoal
trap to cell vacuum line. The rhenium metal is allowed to react at room temperature for
30 min to insure complete dissolution.
3. The vial is then heated at <80oC until dry (2–4 hours) to insure decomposition of excess
peroxide and removal of all moisture until sample has evaporated to dryness.
4. To prepare stock solution of processed sample, add 2 mL of sterile saline solution (0.9%
NaCl) to the processing vessel for an expected final concentration (i.e. based on target
size and irradiation period and HT position) of > 10 Curies per 0.5 mL.
5. The solution is filtered through a 0.22 micron Gelman hydrophobic/hydrophilic filter.

Filtered solution must be colorless and clear, and free of any visible impurities. Record
any comments.
6. Peroxide levels in the stock solution are determined with the peroxide colorimetric test
strip. Peroxide solution must be less than 2 )gm/mL. Record peroxide ppm on Check
Sheet (Note — Because of thickness of leaded glass cell window, it will be difficult to
accurately assess light colors).
7. The pH of processed stock solution should also be determined with pH paper or a pH

meter.
8. For radioassay, take 100 microliters (for example) of sample from stock solution and
dilute with 50 mL of distilled water (Dilution # 1). After making a second dilution of
100 microliters of Dilution 1 with 50 mL of water, take aliquot from Dilution # 2
(100 microliters) out of hot cell for assay of rhenium-186 and rhenium-188 and any
radionuclide contaminants by gamma spectroscopy.
9. Dispense required level of the product into product bottle for shipment.
The saline rhenium-186 perrhenate solution is stable indefinitely.
184
The specific activity and specific volume requirements are specified by the customer.
BIBLIOGRAPHY
KNAPP, F. F., JR., BEETS, A.L., PINKERT, J., KROPP, J., LIN, W.-Y., WANG, S.-Y.,
“Rhenium radioisotopes for radiopharmaceutical development”, (Proc., International Seminar
on Therapeutic Applications of Radiopharmaceuticals, Hyderabad, 1999), IAEA-SR-209,
Vienna.
OAK RIDGE NATIONAL LABORATORY (ORNL), Nuclear Medicine Procedure # 60,
Rhenium-186 Hydrogen Peroxide Processing Procedure, Tennessee.
SHIGETA, N., MATSUOKA, H., OSA, A., KOIZUMI, M., IZUMO, M., KOBAYASHI, K.,
HASHIMOTO, K., SEKINE, T., LAMBRECHT, R.M., J. Radioanalyt. Nucl. Chem. Articles,
205 (1996) 85.
SZELECSENYI, S., TAKACS, S., TARKANYI, F., SONCK, M., HERMANNE, A., Study
186 186 186
of Production Possibility of Re via the W(d,2n) Re Nuclear Reaction for Use in
Radiotherapy, J. Lab. Cmpds, Radiopharm., 42, Suppl. 1 (1999) S912-S914.
185
Half-life : 17.005 ± 0.004 h

187
Production scheme : Re (n,J) 188Re V = 76.4 b
Type of decay and energy : E (MeV) 2.120 (71.1%)

1.965 (25.6%)
Rhenium-188 is a very attractive radioisotope for a variety of therapeutic applications in

nuclear medicine, oncology and interventional cardiology (Knapp, et al., 1997,1998,1999).
Although carrier-free rhenium-188 is conveniently and inexpensively available from the
tungsten-188/rhenium-188 generator system, production of tungsten-188 from irradiation of
enriched tungsten-186 requires a very high thermal neutron flux, which for practical purposes
to provide tungsten-188 with a specific activity >18.5 MBq (0.5 mCi)/mg must exceed about
14 2
5 × 10 n/cm /s (Knapp, et al., 1994; Mirzadeh, et al., 1992). However, neutron activation of
enriched rhenium-187 can also provide rhenium-188 with relatively high specific activity.
Thus, even research reactors with relatively modest thermal neutron flux can be used to
directly produce this important therapeutic radioisotope.
Highly enriched rhenium-187 (97%) metallic targets are usually used for production of
rhenium-188 since they are easily directly oxidized to Re(VII) perrhenic acid. The
concomitant production of rhenium-186 (i.e. from the rhenium-185 impurity) is minimized by
use of highly enriched rhenium-187.
The projected production of rhenium-188 from the radiative (n,J) reaction on enriched
rhenium-187 at various thermal neutron flux values is shown in Fig. 1.
The chemical processing of reactor-irradiated enriched rhenium-187 targets is the same

as described for the production of rhenium-186 by neutron irradiation of enriched rhenium-
185 targets,
1. The target (i.e. aluminum and/or quartz tube) is opened and if a quartz tube is used, the
tube containing the irradiated rhenium-187 target material is carefully opened with a
break tube or cut open, etc. The target material and crushed quartz glass are transferred
into a conical 3–5 mL Pierce processing vessel placed in a heating block. About 2 mL of
30% hydrogen peroxide solution is then added.

A.L. Beets and F.F. Knapp, Jr.,
Nuclear Medicine Programme, Oak Ridge National Laboratory,
186
FIG. 1. Projected reactor production of rhenium-188 from enriched rhenium-187 as a
2. The processing vessel is sealed with a Teflon-lined cap. For processing at ORNL, a
sidearm attachment (evaporation head) is also used and vented through a coarse charcoal
trap to cell vacuum line. The rhenium metal is allowed to react at room temperature for
30 min to insure complete dissolution.
3. The vial is then heated at <80oC until dry (2–4 hours) to insure decomposition of excess
peroxide and removal of all moisture until sample has evaporated to dryness.
4. To prepare stock solution of processed sample, add 2 mL of sterile saline solution (0.9%
NaCl) to the processing vessel for an expected final concentration (i.e. based on target
size and irradiation period and HT position) of > 370 GBq (10 Ci) per 0.5 mL.
5. The solution is filtered through a 0.22 micron Gelman hydrophobic/hydrophilic filter.

Filtered solution must be colorless and clear, and free of any visible impurities. Record
any comments.
6. Peroxide levels in the stock solution are determined with the peroxide colorimetric test
strip. Peroxide solution must be less than 2 )gm/mL. Record peroxide ppm on Check
Sheet (Note — Because of thickness of leaded glass cell window, it will be difficult to
accurately assess light colors).
7. The pH of processed stock solution should also be determined with pH paper or a pH

meter.
8. For radioassay, take 100 microliters (for example) of sample from stock solution and
dilute with 50 mL of distilled water (Dilution # 1). After making a second dilution of
100 microliters of Dilution 1 with 50 mL of water, take aliquot from Dilution # 2
(100 microliters) out of hot cell for assay of rhenium-186 and rhenium-188 and any
radionuclide contaminants by gamma spectroscopy.
9. Dispense required level of the product into product bottle for shipment.
187
The saline rhenium-188 perrhenate solution is stable indefinitely. The product should be
analysed by gamma spectroscopy.
The specific activity and specific volume requirements are specified by the customer.
Although the availability of carrier-free rhenium-188 from the tungsten-188/rhenium-188

generator is the most cost-effective are readily available source, the direct production of
rhenium-188 from irradiation of enriched rhenium-187 targets has the advantage that the
approach can be used with even moderate thermal neutron flux research reactors.
BIBLIOGRAPHY
KNAPP, F.F., JR. Use of Rhenium-188 for Cancer Treatment, Cancer Biotherapy and
Radiopharm., 13 (5) (1998) 337–349.
KNAPP, F.F., JR., BEETS, A.L., GUHLKE, S., ZAMORA, P.O., BENDER, H., PALMEDO,
H., BIERSACK, H.-J., Development of the Alumina-Based Tungsten-188/Rhenium-188
Generator and Use of Rhenium-188-Labeled Radiopharmaceuticals for Cancer Treatment,
Anticancer Research, 17 (1997) 1783–1796.
KNAPP, F.F., JR., BEETS, A.L., PINKERT, J., KROPP, J., LIN, W.-Y., WANG, S.-Y.,
Rhenium Radioisotopes for Radiopharmaceutical Development, (Proc. International Seminar
on Therapeutic Applications of Radiopharmaceuticals, IAEA-SR-209, Hyderabad, 1999),
IAEA, Vienna.
KNAPP, F.F., JR., CALLAHAN, A.P., BEETS, A.L., MIRZADEH, S., HSIEH, B.-T.,
188
Processing of Reactor-Produced W for fabrication of Clinical Scale Alumina based
188 188
W/ Re Generators, Appl. Radiat. Isot., 45 (1994) 1123–1128.
MIRZADEH, S., KNAPP, F.F., JR., CALLAHAN, A.P., Production of Tungsten-188 and
Osmium-194 in a Nuclear reactor for New Clinical Generators, Nuclear Data for Science and
Technology (QAIM, S., Ed.) Spinger Verlag Pub., (1992) 619–620.
188
Samarium-153 (153Sm62)
Half-life : 46.27 h
152
Production scheme : Sm (n,J) 153Sm V = 206 b
Target material : Sm2O3 (152Sm > 98%)
Type of decay and energy (MeV):
beta (E) 0.808 (17.5%) gamma (J) 0.103 (29.8%)

0.705 (49.6%) 0.069 (4.85%)
0.635 (32.2%)
Preparation of target Irradiation

for irradiation
Preparation of Processing Calibration Quality Dispensing

EDTMP solution in hot cell control
Specific target purity: samarium oxide (Sm2O3) 99.999%.

Target purity: samarium oxide (Sm2O3), enriched in Sm-152: 98% or greater.
Target material supplier: ISOTEC INC cat. no. 77–68901.
Target solution: prepared with 10 mg of samarium oxide (Sm2O3) in 2 mL of nitric acid 1%
(HNO3 1%).
1. Reactor used: RA-3, 5 MW pool type research reactor. Thermal fluxes from 2 × 1013 to
1 × 1014 n/cm2s, 4 irradiation boxes with 14 places each one, and 120 hours of continuous
operation per week.
2. Capsule details: the samarium oxide is irradiated in a quartz ampoule; dimensions are 40–
50 mm long, 6–8 mm diameter; oxygen/gas blowpipe is used to seal the ampoule.
3. Mass of target per capsule: 1 mg of samarium oxide.
4. Preparation of target for encapsulation: 0.2 mL of target solution is placed in the quartz
ampoule, taken to dryness in nitrogen atmosphere by heating up to 100–120ºC on a
heating plate. The quartz ampoule, sealed with a blowpipe, is then placed with quartz
wool into an aluminium can (70 mm long, 20 mm diameter), which is cold welded.
Reactor irradiation parameters: neutron flux 4 × 1013 n/cm2/s; irradiation time: 48–54 h.
5. Specific activity achieved at EOI: 14.8–16.8 GBq (400–450 mCi)/mg oxide. Total
activity achieved at EOI: 14.8–16.8 GBq (400–450) mCi.

Alberto Manzini,
Ezeiza Atomic Centre, Comisión Nacional de Energía Atomica,
Camino Borlenghi S.N, Agencia Mimpost 1842, Buenos Aires, Argentina.
189
Flux Irradiation time (days)
(n/cm2/s) 1 2 3 4 5
1,00E+13 56 95 123 142 156
2,00E+13 112 191 246 285 312
3,00E+13 168 287 370 428 468
4,00E+13 225 382 493 570 625
5,00E+13 281 478 616 713 781
6,00E+13 337 574 740 856 937
7,00E+13 393 670 863 998 1093
8,00E+13 450 765 986 1141 1250
Total activity at EOI (mCi/mg oxide)
The hot cell is a sealed box under reduced pressure (15–20 mm of water-reduced
pressure), with remote handling tong, and 10 cm of lead thickness as biological shielding.
Viewing windows are made of lead glass (20 cm thick). The windows are mounted in frames
fitting the interlocking lead brick system, and the space between the glass and the lead frame
is packed with lead yarn. The tong used has a detachable head to enable to change the types of
jaws without removing the tong from the box. A flexible plastic sleeve is attached to the tong
shaft to prevent contamination being carried into the laboratory when the tong is drawn
outwards. In addition there are a few special tools: for opening cans, cutting quartz ampoules,
rigid support for the glass material and a sealing machine for glass vials.
For dispensing a sealed glove box working at reduced pressure is used. The equipment
placed inside consist in a remote operated pipette (5 mL syringe) connected by means of a
plastic tube to a hypodermic syringe, a glass vial containing the radioisotope solution (storage
bottle) placed in a lead pot, a crimper for opening the vial, millipore filters and needles fitting
the pipette for sterilization of the solution when dispensing.
Reagents and chemicals required for processing
EDTMP (ethylene diamine tetramethylene phosphonic acid) .

NaOH (sodium hydroxide, 1 N solution).
H2O (bidistilled water).
EDTMP solution: 150 mg of EDTMP, dissolved in bidistilled H2O (1.5 mL) with NaOH 1N
(2.5 mL) up to pH=8–9. Final volume is 4 mL.
After irradiation the aluminium can and the ampoule are opened in the hot cell.
The active target is dissolved in the EDTMP solution. After 15–20 minutes bidistilled H2O
(2 mL) is added. Final volume is 6 mL. The solution is heated for 45–60 minutes at 75–80ºC.
Total activity calibration is carried out, and bidistilled H2O is added to achieve an activity
concentration of 1.1–1.3 GBq (30–35 mCi)/mL.
190
FIG. 1. Hot cell for the production of 153Sm-EDTMP.
The final solution of Sm–153-EDTMP (act.conc. 1.1–1.3 GBq (30–35 mCi)/mL) is filtered
through Millipore filter 0.22 µm for dispensing. For quality control a 3 mL fraction is
separated.
Radionuclidic purity: determined by J-spectrometry with a GeHp semiconducting detector
associated to a multichannel analyser.
Alcalinity: determined by pHmeter.
Radiochemical purity: determined by thin layer chromatography, using ITLC-SG/H2O. Rf
(Sm3+) = 0. Rf (Sm-EDTMP) = 0.8–1.0.
Sterility: by millipore filter 0,22 µm.
Pirogenity: test on animals. Three rabbits are injected in the ear vein.
Toxicity: test on animals. A lot of five NIH mice are injected with 0.1 mL of the final
solution. The animals remain under observation during 5 hours.
Biodistribution: test on animals. Wistar rats, weigth 200–250 g, i.v. injected (0.2 mL).
Isotonicity: determined by conductimetry.
Radioactive concentration: determined by comparative method in a well-type ionization
chamber.
According to the required activity, a determined volume of Sm-153-EDTMP solution
from the storage bottle is dispensed into a steril evacuated penicillin-type glass vial, sealed
with a rubber stop and an aluminium cap crimped on.
1. Limpid, colorless, water solution.

2. Radionuclide identification: 153Sm.
3. Radionuclidic purity: > 99%.
5. Radiochemical purity: >95%.
191
6. Concentration activity at date of calibration: 740–925 MBq (20–25 mCi)/mL.
7. Specific activity: 14.8–16.8 GBq (400–450 mCi)/mg oxide.
8. Storage conditions: at room temperature.
9. Disposal of waste generated: all the solid material used during the process in the hot cell
is discarded to a polyethylene container placed under the box of the hot cell. A small
quantity of liquid waste is generated in the process. Remaining liquid after dispensing in
the glove box is stored for decay. All the solid material used is discard to a shielded
recipient, and stored for decay.
Intended use of the final product: pain palliation of bone metastases.
Labelling is better carried out when solid target is irradiated and dissolved with the
EDTMP solution. Colloid is formed when liquid solution of target (nitric solution) is
irradiated and diluted with EDTMP solution.
A remarkable difference is noticed when EDTMP concentration is modified in the final
solution. When this concentration is increased, hepatic uptake of the complex diminishes. For
EDTMP concentration a minimum of 10 mg/mL was established.
BIBLIOGRAPHY
COLLINS, C., EARY, J.F., et al., J. Nucl. Med., 34 (1993) 1839–1844.

EARY, J.F., COLLINS, C., et al., J. Nucl. Med., 34 (1993) 1031–1036.
FARHANGHI, M., HOLMES, R.A., et al., J. Nucl. Med., 33 (1992) 1451–1458.
FARMACOPEA NACIONAL ARGENTINA, 6° Edición.
GOECKELER, W.F., EDWARDS, B., VOLKERT, W.A., et al., J. Nucl. Med., 28 (1987)
495–504.
KETRING, A.R., Nucl. Med. Biol., 14 (1987) 223–232.
LEDERER, C.M., SHIRLEY, V.S., Table of Isotopes, 7th Ed., Manual of Radioisotope
Production, Tech. Rep. Series Nº 63, IAEA, Vienna (1966).
VERA RUIZ, H., Boletin OIEA, 1, IAEA, Vienna (1993) 24–27.
192
Scandium-46 (46Sc21)
Half-life : 83.77 ± 0.04 d
45
Production scheme : Sc(n,J)46Sc V = 27 b
Type of decay and energy : E (MeV) 0.3566 (99.996%)
J (MeV) 0.889 (99.98%)
1.120 (99.98%)
Target material : Scandium oxide
Target specifications and peparation

Spec pureSc2O3 (10 mg) (JM Grade) .
Irradiation container
Standard high purity aluminium can of dimensions 22 mm dia × 46 mm ht., cold welded.
Neutron flux : 3 × 1013 n/cm2/s approx.
Irradiation time : 1 month
Yield at EOI : 9.25 GBq (250 mCi)

Standard glove box of dimensions 2 M × 1M × 2 M fitted with 100 mm of lead shielding

wall.
Chemical processing
The irradiated Sc2O3 is transferred to a dissolution flask and 10 mL of 3N HCl is added to it.
The solution is heated to boiling and dissolution of the target is completed. 20 mL of 0.1N
HCl is then added to it and the solution transferred to a storage bottle.

The radioactive concentration is determined by measuring the ion current produced by a
known volume of the solution in a calibrated ion chamber. The specific activity of the product
is calculated from the known quantity of the target irradiated and the activity yield.
Characteristics of the final product

Chemical form ScCl3 in dilute hydrochloric acid.
Radioactive concentration 37–370 MBq/mL.
Radionuclidic purity >99%.
Specific activity >20 GBq/g of Sc .

M. Ananthakrishnan,
193
Scandium-47 (47Sc21)
Half-life : 3.35 d
47
Production scheme : Ti (n,p)47Sc
Type of decay and energy : E-(MeV) 0.4407 (68.4%)

0.6001 (31.6%)
J (MeV) 0.15938 (68.3%)
47
Decay product : Ti (stable)
Target Purity: Enriched 47Ti (94.53% 47Ti, 4.74% 48Ti, 0.35% 46Ti, 0.2% 49Ti, and 0.18%
50
Ti) purchased from Oak Ridge National Laboratory (ORNL). Stable scandium in the target
material shall be kept low to maximize specific activity.
Irradiation parameters, specific activity and total yield at EOB
Reactor : The V-15 or V-16 thimble positions at High Flux Beam

Reactor (HFBR) at Brookhaven National Laboratory
(BNL) (In = 1.5 × 1014 n/cm2/s, En > 1 MeV) and the
HT-5 hydraulic tube position at High Flux Irradiation
Reactor (HFIR) at ORNL (In= 4.6 × 1014 n /cm2/s, En >
1 MeV).
Capsule details : 0.5 cm ID × 5 cm Suprasil (purchased from Heraeus)
quartz ampules.
Target mass : 50–250 mg of oxide.
Irradiation length : 3–5 days.
Specific activity, production yield:
BNL Specific activity: >285 MBq (7.7 mCi)/µg in the “in-
core” positions (V-15 or V-16 thimble positions,
located 13 cm from bottom).
47
Production yield: Sc saturation yield =
47
25.23 MBq/mg Ti.
ORNL Specific activity: >1.23 GBq (33.3 mCi)/µg in the HT
#5 position.
47
Production yield: Sc saturation yield =
47
109.41 MBq/mg Ti.

L.F. Mausner,
Office of Isotope Production,
Medical Department, Brookhaven National Laboratory,
Upton, New York 11973, USA.
194
Processing shall be performed in a shielded hot cell with HEPA filtration in the hot cell
exhaust line.

All reagents used in processing were of analytical grade without further testing or
purification.
Reagents
Dowex AG 50W-X4 cation-exchange resin was purchased in 100–200 mesh size from BIO-
RAD. All glassware was acid washed with HNO3 before use.
Preparation
Dowex AG 50W-X4 resin was purified as follows. Batches of resin were purified by washing
seven times with H2O, each time decanting the fines, twice with 95% ethanol, twice with
H2O, four times with KOH, followed by a H2O rinse to neutrality, and four times with 2 N
HCl followed by a H2O rinse to neutrality. Ion-exchange columns were poured using a H2O
slurry containing the resin. After allowing time for the resin to settle, a quartz wool plug was
placed on the top of the resin bed and the columns were eluted with 5 column volumes of
H2O. Columns were then preconditioned with the same solution containing the sample.
Target dissolution
Enriched 47TiO2 targets were dissolved slowly (t ~ 1–2 h) in very hot H2SO4 (heated to
copious fuming) containing a 10:1 mass ratio of (NH4)2SO4 to Ti. Volumes were reduced with
heating to 10–15 mL and diluted with H2O and H2O2 to obtain a solution (Vf ~ 750 mL)
approximately # 0.15 M in ammonium sulphate, # 3 N in H2SO4 and 0.3% in H2O2. Addition
of peroxide is necessary to oxidize all Ti species in solution to Ti(IV).
Separation procedure
Tests were made with irradiated targets ranging from 50–200 mg of irradiated 47TiO2 or 1.2 g
of Ti metal. The separation procedure is shown schematically in Figure 1. The target solution
was passed over a large column (2 cm ID × 11 cm) containing 35 mL of the cation exchanger
that was previously conditioned 0.2 N HCl. Both Ti and Sc were retained, the Ti appearing as
a large orange band whose width was dependent on the solution acidity. The column was then
washed with 4 column volumes of 0.2 N HCl to further elute traces of the ammonium
sulfate/sulfuric acid solution, followed by 5 column volumes of 1.5 N HCl to elute the
majority of the Ti. More Ti was then eluted with 3 column volumes of 2.5 N HCl along with
trace impurities of Cu, Zn, Co, Pb, or Fe+3. Sc-47 was eluted in nearly quantitative yield with
5 column volumes of 4 N HCl/0.1 N HF., 47Sc was eluted in nearly quantitative yield with 5
column volumes. The 4 N HCl/0.1 N HF fraction containing 47Sc from the first column was
evaporated to near dryness and taken up with 2–3 mL aqua regia to destroy organic residue
which may have eluted with 47Sc from the first column. This solution was evaporated to near
dryness and redissolved in 2–3 mL of 12 N HCl to convert 47Sc to the chloride, followed by
another evaporation to dryness. The residue was taken up in 2–3 mL 0.2 N HCl and this
195
solution was passed over a smaller column (1.1 cm ID × 6 cm, 5.7 mL, Dowex AG 50W-X4
cation-exchange resin). Sc and Ti were again retained, the column was washed with 5 column
volumes of 0.2 N HCl, and Ti was eluted with 5 column volumes of 2.5 N HCl. Scandium-47
was then eluted with 5 column volumes of 4 N HCl/0.1 N HF. This solution was evaporated
to near dryness and the residue was first taken up with ~ 0.3 mL 30% H2O2 and evaporated
with heat to ~ 0. 1 mL, and then treated as described above with aqua regia and HCl. After the
final evaporation with HCl, the solution was transferred with 2–3 mL of 0.5 N HCl from the
beaker to a small rotovap tube. An aliquot was removed for determination of recovery yield
and stable metal analysis (Fe, Zn, Co, Cu, Pb, Sc), and the remaining solution was evaporated
to dryness under vacuum using a rotavapor and redissolved in 0.01 N HCl.
FIG. 1. 47Sc Separation from Ti Targets: Cation exchange with Dowex AG 50W-X4 resin.
Final products are assayed with regard to yield and radionuclidic purity.
Radioactivity measurements
Radioactive samples were assayed by direct J counting on an intrinsic germanium detector
(50 cm3, FWHM 2.0 keV at 1332 keV) connected to a 8192 multichannel analyser. The
196
detector was calibrated against a known mixed gamma solution standard traceable to NIST.
Counting samples were prepared in a plastic vial by dilution of the sample aliquot to 1 mL.
All samples were counted at distances >8 cm from the detector face where coincident
summing corrections are negligible.
Stable elemental Analysis is made with and ICP-AE. From this data, the specific activity may
be determined. Chemical purity limits: <30 µg each of Pb, Mn, Zn, Cu, or Ti (though actual
impurity levels should be kept as low as possilbe).

The final product is intended for use in radiopharmaceutical development by attachment of
47
Sc to the 4-ICE-anti-CEA F(ab’)2 MAb conjugate (4-ICE:MAb = 1.7–3.4) where 4-ICE is
4-isothiocyanatocyclohexyl EDTA.
Physical observations : The final product should be clear and colorless.

Radionuclide identification : by the 159 keV photon (68% abundant).
Radionuclide purity : Radionuclide impurity limits should total <2% of 47Sc
activity.
Solution pH : pH =5 for 47Sc to be conjugated.
Radiochemical purity : The radiochemical purity of 47Sc is determined using
HPLC.
Concentration requirements : Requires 3-fold molar excess of 4-ICE-Mab conjugate
relative to total metals content, requires >185 MBq
(5 mCi)/µg 47Sc.
Shelf life and recommended storage conditions: Shelf life depends on specific activity
requirements of final preparation of antibody conjugate.
If not used immediately, the radionuclide should be
stored at pH < 2.
Waste disposal : Waste disposal is similar as waste disposal for other
radionuclides. Presence of small amounts of 46Sc
extends time period when waste is radioactive.
Preparation and cleanup considerations: Ion-exchange columns are poured fresh for each
production run. Peroxide is stored in a refrigerator and
disposed after its expiration date (generally 6 mo. after
bottle is opened).

To achieve dissolution of target material requires very high heat (vigorous fuming of H2SO4)
and at least a 10-fold excess of ammonium sulphate. Ion-exchange column fractions
containing 47Sc must be rigorously digested with peroxide and aqua-regia to remove organic
residues that co-elute with 47Sc from the columns. Failure to follow these steps can lead to
disappointing labeling results. Further details are given in the references sited below.
BIBLIOGRAPHY
MAUSNER, L.F., et al, Radionuclide Development at BNL for Nuclear Medicine Therapy,
Appl. Radiat. Isot. 49 (1998) 285.
197
Silver-111 (111Ag47)
Half-life : 7.45 d
E
110
Production scheme : Pd (n,J) 111Pd o 111Ag
111
Decay product : Cd
Production process
Ag-111 is a radionuclide with potential application in the field of radioimmunotherapy. It can
easily be prepared by neutron irradiation of palladium according to the nuclear reactions
depicted in scheme 1. Natural palladium consists of a mixture of 6 stable isotopes but only the
upper three neutron capture processes are relevant. For the production of Ag-111 from natural
palladium, the neutron capture of Pd-108 to Pd-109 with subsequent decay to stable Ag-109 is
the most important parallel reaction, since this isotope limits the final specific activity after
the separation of silver (Ag-109 and Ag-111) from target palladium. Therefore, preparation of
Ag-111 from natural palladium results always in carrier added Ag-111 according to the datas
given in Table I.
To yield n.c.a. Ag-111, enriched Pd-110 has to be used instead of natural Pd. 98% isotopically
pure Pd-110 is commercially available, however it is rather expensive. For the processes
described below it has to be recycled, which might cause problems due to long lived
contamination in the original sample (i.e. Ir-192, Hg-203 etc.) which are always present as
impurities in the targets. The specific activities achieved with natural Pd are usually
sufficiently high for the labelling of therapeutically useful biomolecules, the studies have
been performed with nat. Pd only.
Scheme 1. Neutron irradiation of nat. Pd, Pd-102 (1.02%); Pd-104 (11.14%); Pd-105
(22.33%); Pd-106 (27.33%); Pd-108 (26.46%); Pd-110; 11.72%
*111mPd : 5.5 h, 73% IT, 27% E-

111g
Pd : 23.4 min, E-
111m
** Ag: 64.8 s, 99.3% IT, 0.7% E-
111g
Ag : 7.45 d, E-
R. Alberto and P. August Schubiger,
Centre for Radiopharmaceutical Sciences, Paul Scherrer Institute,
CH-5232 Villigen PSI, Switzerland.
198
TABLE I. ACTIVITIES AND AMOUNTS OF AG-109 AND AG-111 PRODUCED UPON
IRRADIATION OF 0.1 G NAT. PD AT A NEUTRON FLUX OF 5 × 1013 n/cm2/s
Irradiation ActEOB ActEOB Amount Amount Aspec.

[h] Pd-109 Ag-111 Ag-109 Ag-111 [mCi/mg]/
[mCi/GBq] [mCi/MBq] [µg] [µg] [GBq/mg]
24 1706/62.9 3.4/125 1.4 0.02 2430/90
48 2217/82 6.5/240 2.84 0.04 2290/85
72 2360/85 9.4/344 4.3 0.06 2190/80
96 2400/89 12.0/440 5.75 0.075 2051/76
144 2400/89 16.5/510 8.6 0.1 1896/70
192 2400/89 20.3/750 11.4 0.13 1760/65
240 2400/89 23.4/860 14.3 0.15 1620/60
480 2400/89 32.7/1200 28.5 0.21 1140/42
960 2400/89 37.7/1380 57.0 0.24 658/24
Principle of the separation process
Since the purification process is special it will be explained in detail. Liquid/liquid extractions
are usually applied for the separation of a component from bulk material, which forms with
high selectivity and stability only compounds with the desired radionuclide. If the process is
repeatedly performed, high purity material can be yielded.
Such specific ligands or phase transfer carriers do not exist for palladium and silver, since
their chemistry is very similar in terms of preferred ligand atoms or ligands. Comparing the
few thermodynamic stability constants reveals, that log K are larger for Pd2+ by about 1–
2 orders of magnitude. Consequently, Pd2+ could be extracted into an organic layer with a
versatile ligand, however, very high accumulation of Ag-111 can obviously not be achieved
by this method. A very slight excess of ligand would transfer Ag+ as well.
Pd2+ and Ag+ differ significantly in their kinetic behaviour Pd2+ is very slowly reacting while
Ag+ is a very fast. The basis of the seapration is, thus, different kinetic behaviour rather then
thermodynamics.
The phase transfer ligand is triphenyl-phosphine (TPP) which forms stable complexes with
Ag+ and Pd2+.
Pd2+ is extracted slower to a concentration which corresponds to about 1 eq. Pd2+ per
TPP. This process can easily be monitored by external radioactivity measurement, since Pd-
109 decomposes to short-lived Ag-109m. After all TPP are coordinated to Pd2+, the TPP
ligands coordinated to Ag+ are slowly released by competition of [Pd(TPP)]2+. The remaining
Ag+ is then again phase transferred back into water.
199
[Pd(TPP)]2+ + [Ag(TPP)n]+ o Ag+ + [Pd(TPP)2]2+
aqueous organic
The original acidic layer is exchanged by a slightly acidic fresh solution Ag+ can be collected
after reextraction in quantitative yield and very high purity. The Pd-TPP complexes are
almost insoluble in aqueous solution. After a certain period of time, Ag-111 is reexctracted
into the fresh aqueous solution.
Detailed experimental procedure

In a typical standard experiment, 0.4 g of Pd metal was irradiated at the Seibersdorf research
reactor over 72 h. After a decay period of about 2–3 days, the material contained about 1.48
GBq (40 mCi) of Ag-111 and still 7.4 GBq (200 mCi) of Pd-109.
Dissolution of Pd to Pd(NO3)2
The irradiated capsule was broken and the aluminium packages transferred to a round bottom
flask. The metallic Pd powder was dissolved in conc. HNO3 (20 cm3) over 12 h at 130oC,
resulting in a dark brown but clear solution. The Pd must completely be dissolved, otherwise
catalytic decomposition of TPP might occure. The solution was then diluted to a final volume
of a 50 cm3 with bidistilled water.
Extraction of Ag+/Pd2+ into Tolune
The aqueous nitric acid solution was transferred nto a round bottom flask equipped with stir
bar and overlayered with 150 cm3 of toluene. The stirring rate was adjusted to a value, where
the two layers did not mix and no toluene drops in water (and vice versa) formed. For
reproducibility of the procedure, this rate should be kept constant. 5 cm3 of a 0.1 M solution
of TPP in toluene were added by means of a syringue. The activity in the organic layer was
monitored either by a J-counting tube focused on the organic layer or by a bypass attached to
the flask continuously flushed by a means of peristaltic pump. The activity in the organic
layer steadily increased. Maximum was reached after about 20 min depending on the tirring
rate. The organic layer turned yellow. At the maximum, about 95% of Ag-111 was in the
organic layer.
Reextraction of Ag-111/Ag-109 into 10-4 M HNO3
After the maximum was achieved, stirring was stopped and the organic layer transferred into
a separation funnel, containing about 10 cm3 of 10-4 M HNO3. For the purity of the product
carefull separation was crucial. Remaining toluene fractions and the 10-4 M HNO3 were
mixed by dropping the aqueous layer continously through the organic layer for about 2h.
After this time period, about 80% of Ag-111 were reextracted into the aqueous solution,
which was separated through the lower end of the funnel. The solution was completely
colourless and even UV/VIS spectroscopy did not show the presence of any Pd2+. Pd2+
contamination was checked by means of ICP-MS, which gave usually less than 1% of Pd
relative to Ag+.
Apparatus and flowchart
A schematized drawing of an apparatus for routine use is given in Scheme 2. In general,

teflon tubes have been chosen for the transfer from one bottle to another. The flask can be
200
normal glass ware with the exception of the last separation funnel, which has to be either from
teflon or better quartz glass. Ag+ has the tendency to adsorb very well on normal glass
probably by ion exchange with Na+ or K+. As long as the aqueous solution was acidic, no
problem with adsorption were encountered since competition of H+ was strong enough.
However, when changing to more physiological buffer solution or to slightly acidic medium,
a steadily growing amount of Ag-111 was found to bind irreversible to glass. In any case,
rubber should be omitted, since any sulfur containing material will adsorb Ag+ very
efficiently.
0.1 g of Pd powder was packed in a aluminium foil. Two of these packages were placed in a
quartz glass ampule and sealed under vacuum. Pd was pruchased in puriss quality from Fluka
AG Buchs/Switzerland.
201
Irradiation parameters and facility of processing
In general, the Seibersdorf Astra research reactor was used for irradiation, in a few exceptions
also the Dutch research reactor at Petten. The amount of target and its quality are described
above. The targets were usually irradiated during a 72 h time period at a neutron flux between
7.7 and 8.3 × 1013 n/cm2/s. The specific activities achieved after the separation process
corresponded in general the data given in Table I. For the processing of the target, hot cells
with negative pressure and charcoal filters were used.
BIBLIOGRAPHY
ALBERTO, R., BLAEUENSTEIN, P. SMITH, A., SCHUBIGER, P.A., An Improved

Method for the Separation of Ag-111 from Irradiated Natural Palladium. Int. J. Appl.
Radiat.Isot., 43 (7) (1992) 869–872.
202
Sodium-24 (24Na11)
Half-life : 14.959 h
23
Production scheme : Na (n, J) 24Na V = 0.53 b
Type of decay and energy : E-(MeV) 1.3907 (99.94%)

J (MeV) 1.369 (100%)
2.754 (99.94%)
Target material : Anhydrous sodium carbonate
Decay product : Magnesium-24
Target Purity : Meets British Pharmacopoeia 1998 requirements.

Enrichment factor : Nil.
Impurity details : Contains 98.5–101.5% Na2CO3 with reference to the
dried substance.
Isotopic composition : Non-enriched material is used.
Supplier : BDH or Merck.
Grade : Suprapur grade.
Reactor used : HIFAR, Lucas Heights, Australia.

Assembly : Hydraulic tube with conveyor unload.
Capsule details : Anhydrous Sodium Carbonate starting material is
placed in a screw top aluminium or titanium inner can,
which in turn is placed in a screw top aluminium or
titanium outer can.
Target mass : 100 mg Na2CO3/capsule.
Target preparation : Dry at 200°C for 4 h.
Reactor neutron flux : ~ 6 × 1013 n.cm-2.s-1 (thermal).
Irradiation time : 8h
Cooling period : N/A.
Expected activity : 9.25 GBq (250 mCi) 24Na, > 5 GBq/g Sodium element.
Processing facility
This material is processed inside a hot cell.

203
This material is prepared by dissolving sodium hydroxide in Water for Injections BP. The
solution is filtered through a 0.22 µm membrane filter into sterile clinbritic vials. The solution
is standardized by titrating against standardized 0.1 M hydrochloric acid, using
phenolphthalein as an indicator. The solution is approved for use with a concentration of
0.18–0.22 M NaOH. Material approved for use is stored under refrigeration, and has an expiry
period of 3 months.
0.2 M Hydrochloric acid solution
This material is prepared by diluting concentrated Hydrochloric Acid AR grade with Water
for Injections BP. The solution is filtered through a 0.22 µm membrane filter into sterile
clinbritic vials. The vials are then autoclaved for 6 minutes at 132°C. The solution is
standardized by titrating against standardized 0.1 M sodium hydroxide solution, using
phenolphthalein as an indicator. The solution is approved for use with a concentration of
0.18–0.22 M HCl. Material approved for use is stored under refrigeration, and has an expiry
period of 6 months.

2. To a 30 mL beaker, add 3 mL of 0.2 M hydrochloric acid, 15 mL of Water for Injections
BP and a teflon coated magnetic stirrer bar.
3. Place beaker on a hot plate-stirrer and with stirring, slowly add the irradiated sodium
carbonate powder. Tap to ensure all powder is removed.
4. Heat until all CO2 evolution has ceased and remove from hot plate and allow to cool for
5 min.
5. Adjust pH to 6–8 with either 0.2 M hydrochloric acid or 0.2 M sodium hydroxide, added
dropwise with constant stirring. Check pH by placing a drop onto pH paper without
touching the pipette to the paper. Repeat until pH is correct.
6. Make up to 20 mL with water for injections BP.
7. Dispense 1 mL into a serum vial, and measure the activity at calibration time and date, in
an ion chamber.
8. Dilute the stock solution to the required activity concentration and mix well.
9. Dispense solution into sterile vials, then cap and seal vials.
Place vials into lead pots of thickness appropriate to activity concentration.
The radioactive concentration must be within 90–110% of the required concentration at the
calibration time and date. Measure a sample in an ionization chamber that has been calibrated
to measure sodium-24.
204
The radionuclidic purity is acceptable if a gamma spectrum analysis identifies 24Na as >99%
of the total gamma emitters
pH
The pH must be between 6.0–8.0. Measure the sample on a pH meter or using a suitable
narrow pH range paper.

Physical form : A clear, colourless aqueous solution contained in a
serum vial.
Chemical form : An aqueous solution of sodium(24Na) chloride.
PH : 6–8.
Specific activity : >5 GBq/g sodium element at calibration.
Radionuclidic purity : >99% 24Na at calibration.
Radioactive concentration : A specified by customer, typically 40 MBq/mL at
calibration.
in the cell is allowed to decay prior to cleaning the cell.
The cell surfaces are then cleaned by swabbing with
lint free cloths liberally doused with isopropanol or
ethanol.
205
Strontium-89 (89Sr38)
Half-life : 50.53 d
88
Production scheme : Sr (n,γ) 89Sr σ = 0.058 b
89
Decay product : Y
Type of decay and energy : β− (keV) 586.1
1495.1

Strontium-88 carbonate, isotopic enrichment 99.0%.
Supplier: Cambridge Isotope Laboratories, USA.
Cat. Number: SRLM-3825.

Irradiation site: MARIA reactor SM-3 reactor
IEA, Swierk, Poland NIIAR Dymitrovgrad, the
Russian Federation
Assembly: vertical channel in berylium block no data

Capsules: quartz ampoule in aluminium quartz ampoule in aluminium
capsule, φ 25 mm, length 88 mm capsule, φ 9 mm, length 60
mm
Sealing: cold welding welding
Mass of target: about 1 g about 6g
Reactor flux: 2.5×1014 n/cm2/s 1.37×1014 n/cm2/s fast neutrons +
1015 n/cm2 /s thermal neutrons
Irradiation time: 5–6 cycles of 100 hours 20 days
The average activity obtained at Maria reactor (calculated at the activation end) was about
110 mCi (4.0 GBq)/g of Sr. Currently the irradiation is not possible; installation of thermal
neutrons converter is planned.
The average activity obtained at SM-3 reactor (calculated at the activation end) is about
900mCi (33 GBq) per target i.e. 0.15–0.2 Ci (5.5–7.4 GBq)/g of strontium.

The hot cell of 100 mm lead wall equipped with manipulators and connected to the separate
ventilation system. Filters on the air outlet: paper-charcoal. Standard under pressure inside the
hot-cell is 20 mm H2O.
The above procedure was provided by

R. Mikloczak
Radioisotope Centre, OTWOCK Svierk, POLATOM, Poland.
206
Irradiated target
Dissolving of target
in 1M HCl
Evaporation
Dissolving in water
and filtration 0.22um
radionuclidic
purity chemical No cooling of short lived
assay radionuclides
Yes
strontium
chloride
Adjustm ent of specific
sodium activity
chloride
class C
determ ination
Labels Distribution to the glass

vials
Vials and
stoppers
Autoclaving
QC on final
product
No Rejected
Y es
Labels T ransport packaging
M Sr-1
FIG. 1. Schematic flow chart of the production process.
207
Hydrochloric acid 36% : reagent, European Pharmacopoeia, supplier Merck
Sodium chloride : reagent, European Pharmacopoeia, supplier Merck
Water for injection : European Pharmacopoeia, supplier POLATOM

The irradiated target material is dissolved in 1 M HCl, evaporated to dryness and dissolved in
water (bulk solution). After in-process control the isotonicity of the solution is adjusted by
addition of NaCl. The solution is filtered on 0.22µm filter and dispensed into glass vials,
sealed and autoclaved.

Parameters of the obtained solution are controlled: pH, assay of strontium and sodium
chlorides, specific activity, radioactive concentration and radionuclidic purity.
Test for radionuclidic purity
Gamma radiation impurities
The measurement is performed by gamma-spectrometry (GC 1520 detector with the volume
of 70 cm3 and resolution of 0.8 keV at 122 keV from 57Co and 1.8 keV at 1332 keV from
60Co). The spectrum is recorded by multichannel analyser AccuSpecA (Canberra) and
Genie2000 software. The volume of 1 ml of the solution in a standard glass vial is measured,
J-radionuclidic impurities are detected at the lowest limit of 5 × 10–5%. In most of the
produced batches J impurities were not exceeding 0.001%.
Beta radiation impurities
Beta radiation impurities are measured by LSC (liquid scintillation count) method in
WALLAC 1411 (LKB) spectrometer with application of liquid scintillator Ultima Gold
(Hewlett Packard). Measured spectrum is identified against theoretical spectrum of 89Sr
available in the spectrometer’s software.
The measurement of the strontium-90 impurity is based on separation of ytrrium-90 (in

equilibrium with Sr-90) from the tested sample by solid phase extraction chromatography.
Test for radioactive concentration
Activity of strontium-89 in the known volume of the solution was measured by Liquid
Scintillation Method. Liquid scintillator Ultima Gold from Packard was used. The results
were calculated by TDK method (the overall uncertainty of the measurement ±3%).
Test for assay of chlorides
Determination of chlorides assay is performed by potentiometric titration with 0.01 N silver

nitrate.
208
Test for specific activity
Determination of strontium assay in the strontium chloride, 89SrCl2 is performed by

complexometric method. In acetone solution Sr2+ and arsenazo III form a complex which
maximum absorbance can be measured in the visible region at O= 640 nm.
89
Specific activity, rs of the SrCl2 solution is determined on the basis of its radioactive
concentration according to the formula:
CR
rs =
C Sr
where
CR is radioactive concentration of the solution [GBq/mL]

CSr is concentration of strontium in the solution [ngSr/mL]
Test for chemical purity

Chemical impurities in the 89SrCl2 solution are determined by ICP-OES spectrometry. In the
inductively coupled plasma optical emission spectrometry (ICP-OES) the liquid sample is
transformed into aerosol in the nebulizer. The very small drops of liquid are injected into the
plasma by a stream of carrier gas. In the plasma the atoms are excited and form ions of the
analytes. Characteristic radiation is emitted and analysed on a polichromator. Each line
intensity is measured on a semiconductor detector SCD. Intensities of the emitted lines in the
recorded spectrum are evaluated. Quantitative measurement needs calibration of the
spectrometer using standard solutions of the analytes. According to European Pharmacopoeia
(monograph 01/2002:1475) the limits for chemical impurities in the 89SrCl2 solution are:
Al < 2 ppm
Fe <5 ppm
Pb < 5 ppm
The detection limits (LDL) for impurities in 89SrCl2 solution are, as follows:
Element LDL Element LDL Element LDL

[µg/ml] [µg/ml] [µg/ml]
Fe 0.30 As 3.90 Cd. 0.23
Cu 0.51 Al 0.36 Si 0.58
Ca 0.25 Ba 0.09 Mg 1.91
Pb 0.73 B 0.28 Mn 0.08
Te 3.18 Zn 0.67 Ni 1.36
Test for pH
Potentiometric pH determination of the radioactive 89SrCl2 with a glass electrode combined

electrode or colorimetric relative method (paper strips). The strips are covering the pH range
specified for the 89SrCl2. Sensitivity of the strips is controlled periodically.
209
Tests Specifications
Identification:
beta-spectrum absorption curve of maximum energy 1.49 MeV
gamma-spectrum Emax = 909 keV
Characters: Clear, colorless liquid
PH: 4.0–7.0
Radionuclidic purity: >99.6%
total beta impurities <0.2%
Assay of strontium chloride: 10.8–19.4 mg/ml
Assay of sodium chloride: 0–3.0 mg/ml
Radioactive concentration: 37.5 MBq/ml
Specific activity: 3.5–6.3 MBq/mg Sr
Chemical purity: overall t 99.9%
Al < 2 ppm
Fe <5 ppm
Pb < 5 ppm
Sterility: sterile
Radiopharmaceutical is delivered in portions (a single patient dose) containing about 4 ml of

solution with total activity of 150 MBq of strontium chloride, 89SrCl2 (certified on 1200 CET
of the day of calibration). The preparation is delivered in glass vials of 10 ml volume sealed
with rubber stopper and aluminum cap. The shielding container is made of lead.
89
Sr-strontium chloride is a radiopharmaceutical used for palliative therapy of multiple
malignant metastases to the skeleton, mainly from prostate and breast cancer.
Shelf-life: 4 weeks from the calibration date.
batch: the processing is performed in single step, which is performed in the destined cells of a
hot cell. Therefore there aren’t any special requirements for cleanup of the facility. Glass vials
for final product dispensing are washed and heated in 250oC prior to use, vials and closures
are autoclaved. The product is administered intravenously after final sterilization. The
requirements of GMP apply to the manufacturing process.
Sr-89
35000
30000
Counts in CPM
25000
20000
15000
10000
5000
0
1 101 201 301 401 501 601 701 801 901 1001
Chanel
FIG. 2. Beta spectrum of Sr-89 recorded in the Wallac 1411 spectrometer.
210
15000
10000
Intensity
5000
0
-5000
0 2000 4000 6000 8000 10000
Energy (keV)
FIG. 3. Gamma spectrum of Sr-89 on GC 1520 detector.
BIBLIOGRAPHY
DEPTULA, C.Z., CHMIELOWSKI, K., KEMPISTY, T., et al., Method of preparation and
application of strontium chloride-89SrCl2 for palliative treatment of painful bone metastases,
Part I. Production method of strontium -89Sr chloride, Problemy Medycyny Nuklearnej
10 (19) (1996) 161–168.
DEPTULA, C.Z., KEMPISTY, T., MARKIEWICZ, A., et al., Quality control methods of
strontium chloride 89SrCl2, radiopharmaceutical for palliative treatment of bone metastases
(Proceedings of the 2nd International Conference of Isotopes, Sydney) (1997) 196–199.
211
Strontium-89 (89Sr38)
Production technological flowchart

Sr-89 is produced by the natural yttrium oxide irradiation (Y-89–100%) in the fast neutron
reactor as result of (n,p) reaction.
The technological flow-cart of Sr-89 radionuclide production:
Yttrium oxide
p
The pellets fabrication, their loading into irradiation device (ID)
p
Irradiation in BR-10 reactor (SSC RF IPPE)
p
Cutting, drying, pellets unloading
p
The yttrium oxide pellets dilution
p
Sr-89 purification from yttrium is carried out by sorption on cationite out of EDTA solution
of pH=4.0
p
Sr-89 final purification is carried out by sorption on cationite out of hydrochloric medium
p
The produced Sr-89 analysis, preparation for fabrication, radiopharmaceutical fabrication out
of Sr-89.

The raw material for Sr-89 production is the natural yttrium oxide, the chemical impurity
content of which is not more than 10-3–10-4% of mass, and the fissile uranium content is not
more than 10-5% of mass. The uranium concentration in the initial product is controlled by the
method of glass track detectors during its brief irradiation in reactor. The method of Sr-89
production does not require the enrichment of the target initial material.
Due to the fact that (n,p) nuclear reaction cross-section is not large it is necessary to load a
significant amount of yttrium oxide into ID with maximally possible density in order to
accumulate the economically acceptable amount of Sr-89.
The process of the pellets pressing and caking in vacuum at t ~ 1600°C has been developed.
The yttrium oxide pellets are put into irradiation device (ID). The pellets are of 18.6mm
diameter, 4.6 – 10.7mm height, 4.16 – 4.44g/cm3 density. The yttrium oxide amount in ID is
330–340g. (Up to 1kg for BOR-60 reactor in Dimitrovgrad).

Institute of Physics and Power Engineering,
Department of Research Reactors, Isotopes and Radiopharmaceuticals,
Obninsk, Kaluga Region, Russian Federation.
212
In order to prevent the irradiated yttrium oxide contamination with fission products (FP)
during the ID unloading and transportation the pellets are put into the quartz ampoules which
are brought into ID after their sealing (3 ampoules into ID). The ID outer diameter is
26.0 mm, length is 832.0mm. ID is made of stainless steel of 06X18H10T. Its tightness is
provided and controlled. That ID is put into the fast neutron reactor core. Sr-89 yield per
ampoule is 150 mCi.

The yttrium oxide irradiation takes place in BR-10 reactor during 45–50 days in the fast
neutron flux of (5 ÷ 8)*1014n/sec.*cm2, the neutron fluence is (2 ÷ 4)*1021n/cm2.
In the chain of nuclear transformations during the Y-89 irradiation by fast neutrons the
probability of Sr-89 accumulation is negligible, Sr-90 accumulation is less than 10-5%,
rhubidium-89 accumulation is about 1% of Sr-89 activity, the strontium stable accumulation
(mainly of Sr-88 >88%) reduces the Sr-89 specific activity from theoretic value–2.9*104C/g
up to (1.6–1.7)*104Ci/g (according to the calculation).

All the operations of the irradiation device unloading out of reactor, its transportation, cutting
and chemical processing have to be remote-controlled ones. The cutting and chemical
processing take place in the hot cells with double air refinement system and the refined air
exhaust through the 100m height pipe. The cell biological shielding has to provide the
standard operation conditions for the personnel. The pressure difference between the
operation room and the hot cell has to be kept not less than 20mm of the mercury column.
The final operations of purification and control and packing are to be carried out in the
shielded sealed box (with 50 mm of lead) with the same pressure difference between the inner
box space and the operation room (20 mm of the mercury column).
That operation section infrastructure has to provide the personnel clothes entire changing, the
possible collection and disposal (storage) of the solid and liquid radioactive waste.
Analysis of the raw material, reagents and chemicals needed for processing
The following materials have to be subjected to the inlet analysis:
– yttrium dioxide — for the chemical admixture content, uranium especially;
– quartz and stainless steel (pipe) — for their certificates compliance;
– chemical agents: nitric acid, EDTA, ammonia solution, hydrochloride acid have to be of
“X4” model and their compliance have to be controlled;
– tributylphosphate of “technical” model is used after washing by soda solution and
saturation with nitric acid.

The technological flow chart of Sr-89 production consists of the following operations:
– the external surface of the quartz ampoules with yttrium oxide is decontaminated by
boiling in 12 M nitric acid with 0.1M hydrofluoric acid, rinsed by distillate; the ampoules
are broken; the pellets with the fragments of quartz glass are put into the basket of the
device-dissolver;
– the pellets are dissolved in 3–4M nitric acid at ~110°C during 22–24 hours; as the acid is
consumed in the process of dissolving 12M nitric acid is added at ~25–30 mL/h flow
rate; the dissolving results in 2.5–2.81 of yttrium nitric acid solution of 120–130 g/L
213
concentration containing 450–500 mCi of Sr-89 and 120–150 mCi of Y-88 (by the end of
irradiation);
– separation of the main part of yttrium (>99%) from Sr-89 is carried out by the yttrium
extraction by 100% tributylphosphate previously saturated with nitric acid. Extraction
takes place from the nitric acid solution of not less than 12–13M acidity. Sr-89 is kept in
liquid phase in these conditions; yttrium is re-extracted from 100%TBP by distillate and
kept in a vessel in the form of nitric acid solution (~2M) during 2.5–3.0 years up to full
Y-88 decay (T1/2 = 100 days); after that yttrium can be used again; Sr-89 purification
from Y-88 factor is not less than 5*103; the further operations of Sr-89 purification are
carried out in the glove boxes of work premises with the use of local shielding;
– Sr-89 further purification from macro (Y) and micro (Rb-86, Fe, Cr, NiO) admixtures is
carried out by the sorption method with the use of cation exchange resins (KU-2, KU-23,
Dawex-50) in NH4+ form, from solution out of 0.1M, EDTA at pH=+4,0; the solution for
Sr-89 sorption on the cationite is prepared by the nitric acid sublimation by the solution
evaporation up to moist salts, dilution in 0.1M nitric acid, the yttrium hydroxide fallen
sediments dilution in EDTA solution at slight warming and the solution bringing up to
pH=4.0 by ammonia at pH-meter device;
– Sr-89 sorption final purification takes place on cationite in NH4+ form with the solution
flow rate ~ 1 mL/min*cm2;
– Sorption column is washed first by 0.1M EDTA solution of pH=4.0 which amount equals
to 5–6 column free volumes and then it is washed out of EDTA by the distillate which
flow rate is 3–5mm/min;
– the column washing by 0.25–0.3M hydrochloride acid takes place in order to put the
sorbent into H+ from which amount equals to 6-8 free volumes (Vfree);
– Sr-89 is desorped into small volume (70–100 mL) by 7M hydrochloride acid of 0.2–
0.3 mL/min*cm2 rate;
– Sr-89 desorbent obtained is gathered into the quartz vessel and analysed regarding Sr-89
content by beta-accounting and regarding radionuclide admixtures at gamma-
spectrometer. As for radionuclide admixtures at that purification phase as a rule only Rb-
86 tracks can be detected in Sr-89 solution;
– Sr-89 final purification is also carried out on the cationites with preliminary sublimation
of 7M hydrochloride acid, the solution acidity correction up to 0.15–0.2M, Sr-89 sorption
on cationite out of that acidity, column washing by 0.2M hydrochloride acid first with
amount equal to 5 free column volumes and then column washing by 0.4–0.45M
hydrochloride acid in order to refine from Rb-86. Rb-86 content is controlled by gamma-
spectrometric method during the washing; Sr-89 desorption is carried out by 4–5M
hydrochloric acid at ~0.1mm/min*cm2 rate into 30–4-mL volume; all the operations of
that phase of Sr-89 purification are carried out in the quartz dishware with the use of
quartz distillate and hydrochloric acid obtained by isothermal method;
– Sr-89 desorbent obtained is carefully boiled down up to the moist salts, diluted by the
hydrochloric acid solution of pH~4,5 and put into injection vials; the product obtained is
the final product, i.e. strontium-89 radionuclide solution.

The sampling and the volume measurements are carried out with the help of calibration
pipette with not more than 2% error.
The product appearance is visually controlled.
The product total activity and concentration activity are defined as follows:
214
The sources are fabricated out of the purified strontium-89 chloride solution by sampling the
definite amount of the liquid, putting it on to the substrate and drying. Sr-89 activity is
defined according to beta-emission at the beta-radiometer. The measurement are carried out
by relative method by comparison with beta-emission of the reference source made of
reference solutions of the first grade.
The result processing is carried out according to the special method. The relative value of the
measurement result total error is not more than ±5%.
The activity of gamma-emitting admixtures is defined with the help of semi-conduction

gamma-spectrometer.
The beta-emitting admixtures (Sr-90, Y-90) content is defined by measuring the activity of Y-
90 recovered out of the solution which acid concentration is 0.4mol/L by the method of
ascending chromotography on the paper impregnated by di-2-ethyl-gexyl-phosphoric acid.
That operation is carried out after ~7 days storage for the yttrium accumulation. Activity is
defined with the help of scintillation beta-spectrometer. Beta spectrometer energy and
efficiency calibration is carried out with the help of the reference Cs-137 sources.
The product Sr-90 activity will correspond to Y-90 activity calculated by the moment of its
recovering according to the formula: A0 = At/e-OT
Chemical admixture determination: The chemical admixture content in Sr-89 product is

defined by atomic-emission method. The reference solutions 50mkl each containing 18
elements-admixtures (Al, As, Ba, Be, Cd, Cr, Cu, Fe, Hg, Mn, Ni, Mg, Pb, Sb, Sn, Tc, Zr) and
the samples 50mkl each are put on the electrodes impregnated by polystyrene with the help of
pipettes. The arc of direct current from the ɂȼɋ-22 spectrum exciting source is used as the
source for the spectrum excitement. ɂɋɉ-30 spectrograph is used for that operation The
spectral lines blackening ('S) is measured with the help of ɂɎɈ-463 micro-photometer.

“Strontium-89 Chloride Carrier-free”
1. Appearance — transparent colorless solution.
2. Concentration activity is not less than 0.5–2.5 mCi/cm3 on delivery day.
3. Radionuclide admixture content on delivery day in% per Sr-89 content:
- beta particles energy from P-32 up to S-35 < 0.2
- Sr-90 <2.3 * 10-4
- gamma-emitting radionuclides <0.4
3
4. Chemical admixture content, mkg/cm :
- Al <2.0
- Fe <5.0
- Pb <5.0
5. Molar concentration of hydrochloric acid, m/L: 0.05–0.5
6. Useful life, days: 50.

After a set of scientific research and calculation and experimental work the target processing
technology has been developed, the Sr-89 produced amounts have been defined in the fast
neutron reactors and the product quality has been defined in several batches. This product has
215
been tested at the US NIST and certified. A number of other foreign companies have tested it
too.
Sr-89 carrier-free production according to the given technology has a number of advantages:
– there is no need to use the enriched Sr-89 target;
– high specific activity of Sr-89 and the low Sr-90 content allow longer
radiopharmaceutical shelf-life;
– the synthesis of the radiopharmaceuticals with the optimal specific activity is possible;
– there are more preferable economical parameters of the process.
216
Sulphur-35 (35S16)
Half-life : 87.51 d
35
Production scheme : Cl (n, p) 35S
Type of decay and energy : E (MeV) 0.167 (100%) Emax
0.049 (Eave)
35
Decay product : Cl

abundance section 1012 n/cm2/s And properties of
of nuclide% barn 1 week 4 weeks Saturation Nuclide formed
32
34
S (n,J) 35S 4.21 0.227 11.5 MBq 42 MBq 212 MBq S(n,p) 32P
(0.31 (1.16 (5.77 Half-life: 14.26 days
mCi)/g S mCi)/g mCi)/g Abundance: 95%
S S
35
Cl (n,p) 35 S 75.77 0.49 338 MBq 1.23 6 GBq 33
S (n,p) 33P
(9.11 GBq (167.2 Half-life: 25.34 days
mCi)/g Cl (33.6 mCi)/g Abundance = 0.75%
35
mCi)/g Cl Cl (n,J) 36 Cl
Cl Half-life: 3.01 × 105 a
35
Cl (n,D) 32P
Target material : KCI

Target EM (GR/AR grade KCl with SO42- content less than 0.001%.
Container Standard 1S aluminium can 22 mm dia and 44 mm ht. cold welded.
Irradiation Heavy water moderated 100 MW DHRUVA or 40 MW Cirus

reactor provides the necessary irradiation facility.
Flux 2 × 5 g KCl irradiated for 3 months at 4 × 10 13n/cm2/s yields

370 GBq (10 Ci) 35 S activity,with Sp.Act.> 9.25 TBq (250
Ci)/mmole of S.

M. Ananthakrishnan,
217
REAGENTS SO4 content
HCl <0.001% All the reagents used

HNO3 <0.001% are of GR/AR
NH4OH <0.001% Grade
KCl Mg, Ca, Fe < 0.001%
PO4 3- < 0.001%
SO 4 2- < 0.001%

The processing is carried out in a glove box 6 feet × 4 feet × 6 feet with Perspex sheets as
wall on two sides and fitted with gloves. Exhaust line connected through a pair of HEPA
filters to the fox provides the required negative pressure in the box which is maintained
slightly below atmosphere.
The process equipment consists of distillation unit, ion exchange alumina column, filter
assembly with G-2 filter and concentration flask.
The process
The irradiated potassium chloride is allowed to cool for a week to allow the decay of 42K
formed. The can is decapped and irradiated KCl powder transferred to a 250 mL beaker,
100 mL 0.1 N HCl (purified by repeated distillation) is added to it and KCl is completely
dissolved. Ion exchange column (1 cm dia and 12 cm height) prepared with chromatography
grade alumina is washed with double distilled water and conditioned with 200 mL 0.1 N HCl.
KCl solution is passed through the column at a flow rate of 0.15 mL per minute and effluent
is collected in a receiver to recover 36Cl isotope. The column is washed with 100 mL 0.1 N
HCl and then with 100 mL double distilled water. 35S activity is eluted with 25 mL 1N
NH4OH followed by 50 mL 0.1 N NH4OH. The eluate is collected and concentrated to
approx. 10 mL and neutralized with 1N HCl. It is passed through a filter assembly (G-2) and
filtrate is collected in a concentration flask. Filtrate is concentrated to near dryness and treated
with 10 mL concentrated HNO3 to remove ammonia. The residual activity is treated with
concentrated HCl (5 mL) twice to remove traces of HNO3 followed by 10 mL double distilled
water. 25 mL double distilled water is added to the flask, solution warmed and allowed to
cool and then 35 S activity is transferred to storage bottle.

Activity assayed in liquid scintillation counter with respect to a known reference sample of 35
S. Specific activity is determined by spectro photometric analysis.
Radionuclitide purity is determined by the aluminium absorption curve for the test sample
compared with that of standard and by absence of any gamma emitting radionuclide.
Acidity is determined by titration against standard alkali.
Radiochemical purity is determined by paper chromatography.
218
Radiochemical form H2 35 SO4 in 0.1 N HCL.
Radioactive concentration 3.7–7.4 GBq (100–200 mCi)/mL.
Radiochemical purity >95% as sulphate.
Specific activity >9.25 TBq (250 Ci/mMole).
Appearance A clear colourless solution.
219
Tellurium-123m (123mTe52)
Half-life : 119.7 ± 0.1 d
122
Production scheme : Te (n,J) 123mTe V = 1.1 ± 0.5 b
Type of decay and energy : J (MeV) 0.159 (84%)

Natural tellurium contains only about 2.59 per cent of tellurium-122 so highly enriched
targets are required for production of tellurium-123m. Enriched tellurium-122 powder is used
as the target material.

Tellurium-123m is reactor-produced by neutron irradiation of enriched tellurium-122.
Although low specific activity of about 37 MBq (1 mCi/mg) is obtained for even long
irradiations (23–24 days; 1 Cycle in the ORNL High Flux Isotope Reactor, HFIR) at high
15 2
neutron flux (2–3 × 10 n/cm /s), the high abundance of the 159 keV (84%) gamma photon
emitted makes tellurium-123m an attractive candidate as a SPECT transmission line source
(Wang, et al., 1995) and a variety of organometallic tellurium-123m-labeled
radiopharmaceuticals have been developed and evaluated (Knapp, et al., 1980; Knapp, et al.,
1981).
Detailed production yields of tellurium-123m in comparison to the estimated production

yields at various time periods as a function of the thermal neutron flux are not available since
122
detailed irradiation studies have not been reported and the cross-section data for Te are not
well known.

123m
An adequately shielded hot cell or shielded glove box, dependent upon the levels of Te
handled, is required for processing the irradiated target.

Reactor irradiation of the metallic tellurium-122 target material can often result in the
formation of a molten target mass that solidifies hard when cooled. The typical chemical
processing of reactor-irradiated enriched tellurium-122 target involves oxidation to telluric
acid. For many chemical reactions involving initial chemical dissolution, the tellurium is
usually required as a fine powder followed. Tellurium-123m powder is thus obtained from the
telluric acid solution by reduction of the tellurium with sulfur dioxide to the tellurium
precipitate which is recovered by centrifugation or filtration as described below.

M. Du, C., A.P. Callahan and F.F. Knapp, Jr.,
220
1. The irradiated tellurium-122 target is dissolved in concentrated HNO3 by heating in a
o
sand bath at a temperature of 90-100 C. Aliquots are taken for counting to accurately
determine the production yield.
2. The solution is then taken to incipient dryness, and the product dissolved in 5 mL of HCl
and the solution taken to dryness again.
3. At incipient dryness, 5 mL of concentrated HBr is added.
4. The deposit is dissolved by adding two 5 mL alquots of 3M HCl.
5. Small aliquots of hydrazine hydrate (N2H4H2O, MW 50.07) are added and the metallic
tellurium precipitates as a fine powder which is recovered by low speed centrifugation.
6. As an alternative procedure (Knapp, et al., 1980), after dilution of the HCl solution of
telluric acid in 200 mL of distilled water, 5 gm of NaBr is added and the solution boiled
for 30 min, cooled, and sulfur dioxide gas is slowly passed through the solution (about 2
bubbles/sec) for 2 hours. The metallic tellurium precipitates as very fine powder which is
recovered by low speed centrifugation.
7. The powder is re-suspended in with water and centrifuged three times, and then dried in
o
an oven at 140 C or under a heating lamp. This material is then ready for tellurium-123m
source fabrication.

The tellurium-123m should be assayed by gamma spectroscopy and solution of tellurium-
123m are generally stable indefinitely and can be dispensed as required.

The recovery of tellurium-123m by this procedure is generally greater than 90%.
BIBLIOGRAPHY
KNAPP, F.F., JR., Selenium and Tellurium as Carbon Substitutes, Radiopharmaceuticals-
Structure-Activity Relationships (SPENCER, R.P., Ed.) Grune and Straaton, Inc. (1981) 345–
391.
KNAPP, F.F., JR., AMBROSE, K.R., CALLAHAN, A.P., Tellurium-123m-Labeled-23-
(Isopropyl Telluro)-24-nor-5D-Cholan-3E-ol: A New Potential Adrenal Imaging Agent, J.
Nucl. Med., 21 (1980) 251–257.
WANG, H., JASZCZAK, R.J., MCCORMICK, J.W., et al., Experimental Evaluation of a
Tellurium-123m Transmission Source to Determine Attenuation Maps for SPECT, IEEE
Trans. Nucl. Sci., 42 (1995) 1214–1218.
221
Thallium-204 (204Tl81)
Half-life : 3.78 years
203
Production scheme : Tl (n,J) 20481Tl
81

Reaction Isotope Cross- Activity of element at
abundance section 1012 n/cm2/s
of nuclide% barn
One week Four weeks 1 year
203
81 Tl (n,J) 204
Tl
81
29.52 11.4 0.94 mCi/g 3.75 mCi/g 45mCi/g

E- 0.7637 MeV 97.1%
E.C. 2.9%
Target material : Thallium metal (J.M.)

Target 1 g Thallium metal (Johnson Matthey).
Container Standard 1S aluminium can 22 mm dia and 44 mm ht.

cold weld sealed.
Irradiation 1.year
Flux Approx. 5 to 6 × 1013 n/cm2/s .
Typical production 1.0–2.0 curies.

yield
Type of facility for Standard glove box 6 feet × 4 feet × 6 feet.

processing Under negative pressure (2–3cm WG.
Chemical process
The can is opened and the irradiated sample transferred to a 250 mL dissolution flask. 30 mL
IN H2SO4 and 5 mL 30 percent v/v H2O2 is added to it and solution refluxed for one hour to
complete the dissolution. Excess H2O2 is boiled off and active solution transferred to storage
bottle.

M. Ananthakrishnan,
222
Extra care is taken to maintain the negative pressure in the glove box during the entire period
of processing and extra hand glove used to carry out any operation in the box to avoid
contamination.

The radioactivity is assayed by beta counting in a Geiger Muller Counter. Chemical form: As
Thallous sulphate in approx. IN H2SO4.
Radionuclide purity is determined by beta absorption (in aluminium) analysis and gamma ray
spectrum.
Specific activity is determined from the known quantity of target taken for irradiation.

Radiochemical form Thallous sulphate in approx. 1 N.
H2SO4 solution.
Radiocactive concentration 2–10 mCi/mL (74–370 MBq/mL).

Specific activity >10 GBq/g Tl.
223
Thulium-170 (170Tm69)
Half-life : 128.6 d
169
Production scheme : Tm (n,J)170Tm

Reaction Isotopic Cross Activity of element at
Abundance Section 1012 n/cm2/s
of nuclide% barns
One week Four Weeks Saturation
169
Tl (n,J)
69
170
69Tl 100 105 1.37 GBq 15 GBq (1.41 370 GBq
(373 mCi)/g Ci)/g Tm (9.99 Ci)/g
Tm Tm
Type of decay and energy : E(MeV) 0.884 (18.3%)

0.968 (81.5%)
J (MeV) 0.084 (2.48%)
EC (0.15%)
IC (20.79%)
170
Decay product : Yb and 170Er.
Target material : Spec. pure Tm2O3 (Johnson Matthey).

Target Sp.pure Tm2O3 (Johnson Matthey) 50–100 mg.

weld sealed.
Irradiation 1–2 weeks.
Flux Approx. 2–4 × 1013 n/cm2/s.
Type of facility for Standard glove box 1.5 m × 1.2 m × 1.5 m.

processing Under negative pressure (2–3 cm WG).
Reagents used: All the reagents used are of AR/GR grade.

M. Ananthakrishnan,
224
Chemical processing
After irradiation the can is opened and Tm2O3 powder is transferred to a 100 mL beaker.
10 mL 3N HCl solution is added to it and boiled to complete the dissolution of target.
Solution is concentrated to minimum volume and 20 mL of 1.0 N HCl added to it and activity

Radioactive assay is done by beta counting in a G.M.Counter. Radionuclide purity is
determined by beta absorption analysis. Specific activity is calculated from the known weight
of target used for irradiation.

Radiochemical form TmCl3 in HCl solution.
Radioactive concentration 74–370 MBq/mL.
Specific activity >50 GBq/g Tm.
Acidity Approx. 1N with reference to HCl.
225
Tin-113 (113Sn50)
Half-life : 115 d (113gSn)

112
Production scheme : Sn (n,J) 113Sn V = 1.0 b
Vm = 0.3 b and Vg = 0.71 b

113m
Sn (21.4 min) 91.1% IT
8.9% EC
J 0.077 (0.5%)
113g
Sn (115.09 d) EC
J 0.3917 (65%)
0.2551 (2.11%)

The radionuclide 113Sn decays by electron capture to 113mIn with a physical half-life of 115
days. Tin-113 is obtained by irradiation of isotope enriched metallic tin-112 in nuclear reactor
in the thermal neutron flux.
Tin-112 isotope enriched 81.7% in metallic form is used as a target material.
Trade name: Sn-112 metal.
Isotopic composition [%].
Sn-112 Sn-114 Sn-115 Sn-116 Sn-117 Sn-118 Sn-119 Sn-120 Sn-121 Sn-122
81.7 0.44 0.06 3.47 1.52 4.83 1.35 5.43 0.55 0.65
Chemical impurities [%]
Fe Al. Si Cr Ni Cu Pb Sb Bi Zn As
0.007 0.003 0.004 <0.003 0.004 0.006 0.003 <0.003 <0.002 0.070 <0.002
Supplier: Chemotrade, Chemiehandelsgesellschaft mbH.

Irradiation site: SM-3 reactor, NIAR Dymitrovgrad, the Russian Federation.
Assembly: vertical irradiation channel in aluminium block
Capsules: quartz, I 6, length 40 mm.
Sealing: welding.
Mass of target: 100–200 mg.
Reactor flux: a1015n/cm2/s.
Irradiation time: 40 days.
The average activity obtained (calculated at the activation end) is about 30 mCi/mg Sn.

K. Novak
Radioisotope Centre
Polatom, Otwock, Swierk, Poland.
226
The hot cell of 100 mm lead wall equipped with the manipulators and connected to the
separate ventilation system. Filters on the air outlet: paper — charcoal. Standard under
pressure inside the hot-cell is 20 mm H2O.

Zirconium (IV) oxide chloride octahydrate: GR for Analysis, Merck
Ethyl alcohol 96%: pure for analysis, supplier: Polish Chemicals
Hydrochloric acid 36%: reagent Ph.Eur., supplier Merck
Purified water: deionized water, Elix 10 system, Millipore
Ammonia solution 25%: GR for analysis, Merck
Potassium permanganate: GR for analysis, Merck

113
Sn is used for production of isotope generators 113Sn/113mIn. Eluate of the generators
contains indium-113m in the chemical form of chloride, 113mInCl3. Indium-113m is a
radionuclide which decays by J-radiation with a T1/2= 1.66 h and Emax= 0.392MeV.
The solution of tin-113 is loaded on the generator column containing zirconium oxide. Then
the column is washed with 0.05N HCl. After the equilibrium between tin-113 and indium-
113m is reached the generator is eluted with 0.05 N HCl. Indium-113m is present in the eluate
as In(III). Production steps are described below.
Preparation of zirconium oxide
Zirconium oxide chloride octahydrate is dissolved in water and heated to 50oC, 0.1N NH4OH
is added to precipitate zirconium hydroxide. The precipitate is washed out of chlorides and
dried in 120 oC for 24 hours. After drying the glassy precipitate of zirconium oxide is ground
and sieved. The fraction between 0.250 mm and 0.125 mm is used for production of the
generator columns.
Target dissolving
After opening the container and cutting off the quartz capsule the irradiated target is dissolved
in concentrated hydrochloric acid. Tin dissolves completely within 24 hours, the process can
be faster when the solution is heated.
Preparation of hydrated chloride Cl2×8H2O for oxidation of tin
React potassium permanganate with hydrochloric acid in the glass reactor. Collect produced
chloride into the water trap and cool the solution below 8oC to get saturated chloride solution.
Yellow crystals of Cl2×8H2O are formed. Filter the solution and separate the crystals.
Oxidation of tin
Absorption of tin-113 on the zirconium oxide is the most efficient when it is oxidized to tin
(IV), SnCl4. To the solution with dissolved target the Cl2×8H2O dissolved in 50 mL of water
is added. The volume of the solution is adjusted with water to obtain final concentration 0.4 N
HCl.
227
A portion of 0.1 mL is taken for radionuclidic purity control and of 1 mL for radioactive
concentration test. Portions containing required activity of 113Sn are dispensed onto the
generator columns. Then generator column is washed with 100 mL of 0.05 N HCl. Final
mounting of the generator elements is made.

For the elution of the generator the vacuum vials and eluent (0.05N HCl) vials are needed. Six
elutions (each made with 3 times 6 mL of eluent) are made for control of the generator.
Sample volume of each fraction — 6 mL. Usually it is not recommended to use the third
fraction because of low activity of 113mIn. Every single generator is controlled.
Elution yield of 113mIn should not be less than 75% of the nominal activity (with respect to
113
Sn parent — daughter decay scheme). Nominal activity of the generator is 4–8 GBq. Over
90% of indium-113m activity is collected in the first 10 mL of eluent.
Other nuclides present next to tin-113 in the irradiated target: 117mSn (T1/2 =13.6d), 119m
Sn
(T1/2 = 293.1d), 121Sn (T1/2 =27.06h), 123mSn (T1/2 =40m), 125gSn (T1/2 =9.64d).
The radinuclidic purity of the eluate of 113mInCl3 from isotope generator 113Sn/113mIn is
controlled by gamma-spectrometry with use of Ge(Li) detector (20cm3 FWHM = 4.0 keV for
1332 keV of 60Co). The activities of characteristic lines corresponding to each isotope are
measured:
190 keV for 114mIn
391 keV for 113Sn
427.87 keV for 125Sb
and related to the total activity of 113mIn in the sample. The limit for the total activity of
radionuclidic impurities measured in the eluate is 0.1%, related to indium-113m.
Chemical purity
Eluates are controlled for chemical contamination by DC spectrography. The limits for
the impurities are:
Zr,As,Pb,Cr,Ni,Fe <5 µg/mL
Ag <10 µg/mL
Zinc can be present in the eluate.
In the environment of 0.05N HCl used as an eluent for the generator, indium chloride InCl3 is
completely dissociated and no other electrovalence states of indium than In3+ are present in
the solution.
Stability of the generator
The generator can be used over the period of 6 months and it is stable from the chemical point
of view. No changes in the performance of the generator have been observed over that period.
228
Applications
Indium-113m was popular in eighties and seventies as a diagnostic agent, used for labelling of
kits such as DTPA, Phytate, colloid etc. It’s production is much cheaper than indium-111 and
therefore 113mIn still can be used as a model radionuclide in research studies. Because of its
short half-life and gamma-radiation, indium-113m is presently used as a tracer in various
technical experimental studies.
Product characteristics
Tests Specifications
Identification:
spectra identification gamma ray spectra confirms

prominent photon of 392 keV
Chemical purity
Zr, As, Pb, Cr, Ni, Fe <5 µg/mL

Ag <10 µg/mL
Radionuclidic purity not less than 99.9%
Elution yield not less than:

75% of nominal activity
Shelf-life of the generator: 6 months.
Disposal of generated waste
Low radiactive concentration liquid waste is produced when generator column is being
washed after tin-113 deposition.
batch
– Preparation of zirconium oxide and tin oxidation agent is performed in a laboratory fume-
hood.
– Dissolving of target, oxidation to tin(IV) and dispensing of the dissolved tin-113 on the
generator columns is performed in the destined cells of a hot cell. Therefore there aren’t
any special requirements for cleanup of the facility. Glass vials for final product
dispensing are washed and heated in 250oC prior to use and closures are washed and
autoclaved.

Efficient oxidation of tin-113 is essential for its good absorbtion on the zirconium oxide.
229
Tin-117m (117mSn50)
Half-life : 13.6 ± 0.04 d

116
Production scheme : Sn (n,J) 117mSn V = 6 ± 2 mb
117
Sn (n,n’) 117mSn
Type of decay and energy : E (MeV) J (MeV)

0.1268 (64.9%) 0.15856 (86.4%)
0.15156 (26.2%) 0.15602 (2.11%)
0.12936 (11.7%)

Tin-117m is an attractive radioisotope for use in radiopharmaceuticals, particularly for
therapeutic applications, such as bone pain palliation (Oster, et al., 1985; Srivastava, et al.,
1985), because of the emission of low energy conversion electrons with energies of
0.126 MeV (64%) and 0.152 MeV (26.1%), and also the emission of a gamma photon with
energy of 158.5 keV. In a research reactor, tin-117m can be produced by two reactions,
involving either the radiative neutron capture of enriched tin-116 or the neutron inelastic
reaction on enriched tin-117. The later reaction (Fig. 1; Mirzadeh, et al., 1997) is the most
attractive at least in higher flux reactors since specific activity values of about two times
higher than the radiative capture reaction can be achieved.
FIG. 1. Production yields of tin117m by the inelastic pathway.

230


Dependent upon the subsequent chemical requirements, tin-117m can be processed in a
number of ways. For preparation of tin-(IV)-117m-DTPA agent for bone pain palliation, the
target is dissolved under rigorous oxygen-free conditions by dissolution in HCl. For
preparation of organometallic compounds of tin-117m for radiopharmaceutical applications,
the metallic tin-117m is converted to tin tetrachloride by reaction with chlorine gas (Woo, et
al., 1979; Knapp, et al., 1981). The tin-117m-tetrachloride is a useful starting material for
conversion to a variety of alkyl tin chlorides (Woo, et al., 1979; Knapp, et al., 1981) which
can also be readily converted to the lithium salts, such as lithium trimethyl tin-117m, via
lithiation with metallic lithium metal (Knapp, et al., 1981).

The radiochemical purity is assessed by gamma spectroscopy.

Specifications of the product will depend upon the particular application. Generally, the tin-
117m powder is subsequently processed as described above for a particular chemical
transformation.

Although tin-117m has not been widely used in radiopharmaceuticals, the use of tin(IV)-
117m-DTPA for bone pain palliation is an attracive application which is being evaluated in
patient trials. The major impediment for wider use of this radioisotope is the low specific
activity of tin-117m produced in research reactors.
BIBLIOGRAPHY
KNAPP, F.F., JR., Tin-117m Radiopharmaceuticals: Effects of Structural Modifications on
117m
the Adrenal Uptake of Steroids Labeled in the Sidechain with Sn (Proc. International
Symposium on Medical Radionuclide Imaging, Heidelberg, 1980), I, International Atomic
Energy Agency (IAEA-SM-247/89), Vienna (1981).
MIRZADEH, S., KNAPP, F.F., JR., ALEXANDER, C.W., MAUSNER, L., Evaluation of
Neutron Inelastic Scattering for Radiosiotope Production, Appl. Radit. Isot., 48 (1997) 441–
446.
OSTER, Z.H., SOM, P., SRIVASTAVA, S.C., FAIRCHILD, et al., The Development and In
Vivo Behaviour of Tin Containing Radiopharmaceuticals, II. Autoradiographic and
Scintigraphic Studies in Normal Animals and in Animal Models of Bone Disease, Int. J.
Nucl. Med. Biol., 12 (1985) 175–184.
231
SRIVASTAVA, S.C., MEINKEN, G.E., RICHARDS, P., et al., The Development and In
Vivo Behaviour of Tin Containing Radiopharmaceuticals, I. Chemistry, Preparation, and
Biodistribution in Small Animals, Int. J. Nucl. Med. Biol., 12 (1985) 167–174.
WOO, D.V., KNAPP, F.F., JR., BUTLER, T.A., CALLAHAN, A.P., An Efficient Micro-
scale preparation of Tin-117m Tin Tetrachloride — A pivotal Intermediate for the Synthesis
of Tin-117m-Labeled Radiopharmaceuticals (Proc., 2nd International Symposium on
Radiopharmaceuticals, Seattle, Washington, 1979) Society of Nuclear medicine, New York,
(1979) 147–154.
232
Tungsten-188 (188W74)
Half-life : 69.4 d
186
Production scheme : W (n,J) 187W (n,J) 188W
FIG. 1. Production and decay scheme for tungsten-188.
Tungsten-188 is reactor-produced by double neutron capture on tungsten-186 as summarized

in Figure 1, and is primarily used as the parent for the tungsten-188/rhenium-188 radionuclide
generator system (Knapp 1998; Knapp, et al., 1997; Mirzadeh, et al., 1997; Knapp, et al.,
1994; Kamioki, et al., 1994; Callahan, et al., 1989; Mirzadeh, et al., 1992).
188
Decay product : Re

Highly enriched and highly purified tungsten-186 is required for production of tungsten-188
to eliminate or minimize radionuclide impurities formed during the irradiation process. Either
enriched granular tungsten-186 metal powder targets or granular tungsten oxide targets have
been used, but the present preferred route uses the metal targets (Knapp, et al., 1994). More
recently, the use of high density, pressed, enriched tungsten-186 targets has been described as
an alternative method to increase the target mass per irradiation volume (Mirzadeh, et al.,
1998).
The use of tungsten-186 with enrichment greater than 96% will provide the highest purity
tungsten-188 via the double neutron process.
Iridium-192 and osmium-191 are two radionuclide impurities which are formed during
reactor irradiation of tungsten-186 (Figure 1) and are thus always present in reactor-produced
tungsten-188. Both of these impurities can be subsequently removed, however, when the
rhenium-188 daughter is obtained by generator elution and subsequent sequential post elution

233
passage through an alumina SepPak, to remove any possible tungsten-188 breakthrough
(Callahan, et al., 1989), and then the cation/anion tandem concentration system (Knapp, et al.,
1998; Guhlke, et al., 1997).
As an example, 97.5% enriched W-186 is available from the Oak Ridge National Laboratory
(ORNL) Isotope Production and Distribution Program (IPDP).

Because the production of tungsten-188 from enriched tungsten-186 is a double neutron
capture process, the production yield is a function of the square of the neutron flux. For this
reason, a very high neutron flux is required for the production of tungsten-188 (Knapp, et al.,
1997), probably greater than 8–10 × 1014 n/cm2/s (Knapp, et al., 1998). The projected
production yields as a function of flux are shown in Figure 2. Because of the high 12 b “burn-
up” cross-section estimated for tungsten-188 (Mirzadeh, et al., 1997), the actual production
are lower than predicted.
FIG. 2. Predicted specific activity values for tungsten-188 produced at various thermal
neutron flux values.

A shielded radiochemical hot cell is required for processing any significant levels of tungsten-
188. In addition, because of the high energy gamma emissions (479 keV, 23.4%; 685 keV,
29.2%) from the short-lived intermediary tungsten-187 (t1/2 23.8 hours), Curie-level batches
of tungsten-188 require a 7–10 day decay period, for example, to allow decay of tungsten-187
to levels which allow shipment as a Type A shipment.

The processing of tungsten-188 is generally conducted in a quartz glass vessel. All reagents
and chemicals should be analytical grade.
234
FIG. 3. Processing of reactor produced tungsten-188.
The chemical processing procedures are summarized in Figure 3. Processing of the granular
tungsten metal and tungsten oxide targets involves dissolution in sodium hydroxide solution
containing hydrogen peroxide solution to form sodium tungstate.

Following dissolution of the irradiated target, the solution is then filtered and aliquots
analysed using a germanium crystal detector, if available, to determine the specific volume
levels of tungsten-188, osmium-191 and iridium-192, and any other radionuclidic impurities
which may be present. The basic sodium tungstate solution can be stored indefinitely.

Processed tungsten-188 is generally stored as sodium tungstate in sodium hydroxide solution,
which is acidified just prior to loading, for example, of the alumina-based tungsten-
188/rhenium-188 generator system (Knapp, et al., 1998; Knapp, et al., 1997; Knapp, et al.,
1994; Callahan, et al., 1989). The specific volume requirements depend upon the size
generators which are prepared. For large, clinical-scale generators (500–1000 mCi tungsten-
188), it is convenient to have specific volume solutions >20 mCi/mL. The specific activity
values also depend upon the size generators which are required, since the binding capacity of
the alumina column is finite (Kamioki, et al., 1994), although this parameter has not yet been
accurately determined using high levels of activity. At ORNL, the maximum levels of
tungsten which are used for generator fabrication are <80–90 milligrams of tungsten per gram
of the aluminum oxide column adsorbant.

Enriched tungsten-186 with very high chemical purity should be used for reactor production
of tungsten-188. We have noted that low levels of cobalt-60, and antimony-124 and
antimony-125 can be formed during irradiation if even very low levels of cobalt-59 and
antimony-123/124, respectively, are present in the target material because of the high thermal
neutron cross section values for neutron capture.
235
If any aluminum from the irradiation vessel or from shims used in the target holder is
dissolved during the target processing, low levels of colbalt-60 can also be introduced into the
tungsten-188 product by this route. It is recommended that silicon wool or some other inert
material be used if shims are required for loading the quartz tube containing the target
material into the aluminum capsule. Any aluminum which may have been introduced can be
removed by acidification to <pH 8 followed by filtration or centrifugation.
At high neutron flux such as in the ORNL HFIR, an unidentified black solid is also usually
formed which is difficult to solubilize in base, and even under oxidizing conditions with
hydrogen peroxide and potassium hypochlorite (Knapp, et al., 1994). Processing of metal
powder targets involves the oxidation and dissolution in base. In contrast, the pressed targets
are efficiently processed by oxidation in an air stream at high temperature (>750 oC). The
green-colored tungsten oxide which is formed is then dissolved in sodium hydroxide to form
sodium tungstate (Mirzadeh, et al., 1998).
The recovery of enriched tungsten-186 from used tungsten-188/rhenium-188 generators has

also been described (Mustaq, 1996).
BIBLIOGRAPHY
CALLAHAN, A.P., RICE, D.E., KNAPP, F.F., JR. “Rhenium-188 for Therapeutic
Applications from an Alumina-Based W-188/Re-188 Radionuclide Generator System”,
NucCompact, 20 (1989) 3–6.
KAMIOKI, H., MIRZADEH, S., LAMBRECHT, R.M., KNAPP, F.F. JR.,
DADACHOVA, E. "Tungsten-188/Rhenium-188 Generator for Biomedical Applications,"
Radiochim. Acta, 65, 39–46 (1994).
KNAPP, JR., F.F., CALLAHAN, A.P., BEETS, A.L., MIRZADEH, S., HSIEH. B.-T.
"Processing of Reactor-Produced Tungsten-188 for Fabrication of Clinical Scale Alumina-
Based Tungsten-188/Rhenium-188 Generators," Appl. Rad. and Isot., 45 (1994) 1123–1128.
KNAPP, F.F., JR., MIRZADEH, S., BEETS, A.L., Reactor Production and Processing of
Therapeutic Radioisotopes for Applications in Nuclear Medicine,” J. Radioanalyt. Nucl.
Chem. Lett., 205 (1996) 93–100.
KNAPP, F.F., JR., BEETS, A.L., GUHLKE, S., ZAMORA, P.O., BENDER, H.,
PALMEDO, H., BIERSACK, H.-J., “Development of the Alumina-Based Tungsten-
188/Rhenium-188 Generator and Use of Rhenium-188-Labeled Radiopharmaceuticals for
Cancer Treatment,” Anticancer Research, 17 (1997) 1783–1796.
KNAPP, F.F., JR., BEETS, A.L., MIRZADEH, S., GUHLKE, S., “Use of a New Tandem
Cation/Anion Exchange System with Clinical-Scale Generators Provides High Specific
Volume Solutions of Technetium-99m and Rhenium-188,” (Proc. International Trends in
Radiopharmaceuticals for Diagnosis and Therapy) IAEA TECDOC-1029, (1998) 419–425.
KNAPP, F.F., JR., “Radionuclide Generators in Nuclear Medicine: Present Status and Future
Perspectives,” Proceedings, International Trends in Radiopharmaceuticals for Diagnosis and
Therapy, IAEA TECDOC-1029 (1998) 485–495.
KNAPP, F.F., JR., BEETS, A.L., MIRZADEH, S., ALEXANDER, C.W., HOBBS, R.L.,
“Production of Medical Radioisotopes in the ORNL High Flux Isotope Reactor (HFIR) for
Cancer Treatment and Arterial Restenosis Therapy after PTCA” (Proc. 13th Radiochemical
Conference, Marianske Lazne, Czech Republic, 1998).
236
KNAPP, F.F., JR., “Use of Rhenium-188 for Cancer Treatment,” Cancer Biotherapy and
Radiopharm., 13 (1998) 337–342.
KNAPP, F.F., JR., BEETS, A.L., PINKERT, J., KROPP, J., LIN, W.-Y., WANG, S.-Y.,
“Therapeutic Applications of Rhenium-188 — A readily Available Generator-Derived
Radioisotope” (Proc. International Seminar on Therapeutic Applications of
Radiopharmaceuticals, IAEA-SR-209, Hyderabad, 1999).
MIRZADEH, S., KNAPP, F.F., JR., CALLAHAN, A.P., “Production of Tungsten-188 and
Osmium-194 in a Nuclear Reactor for New Clinical Applications” (Proc. International
Conference on Nuclear Data for Basic and Applied Sciences, Julich, 1991), Nuclear Data for
Science and Technology, (Qaim, S., Ed.); Spring Verlag, (1992) 619–620.
MIRZADEH, S., BEETS, A.L., KNAPP, F.F., JR., “HFIR-Produced Radioisotopes of
Current Medical Interest” (Proc. Sixth Workshop on Targetry and Chemistry, Vancouver,
B.C., Canada, 1995, Link, J. M., Ruth, T.J., Eds.) (1996) 129-131.
MIRZADEH, S., KNAPP, F.F. JR, LAMBRECHT, R.M., “Burn-up Cross-section of
Tungsten-188,” Radiochemica Acta, 77 (1997) 99–102.
MIRZADEH, S., DU, M., BEETS, A. L. AND KNAPP, F.F., JR., “Thermochromatographic
Separation of Medical Radioisotopes,” Industrial and Engineering Research (Proc. ACS
Symposium on Nuclear Separation for the Radiopharmacy, National Meeting, Boston, 1998).
MUSTAQ, A. “Recovery of Enriched 186W from Spent 188W/188Re generators,” Appl. Radiat.
Isot., 47 (1996) 727–729.
237
Ytterbium-169 (169Yb70)
168
Production scheme : Yb (n,J) 169Yb
Type of decay and energy : J (MeV)
0.0631 (44.2%)
0.0936 (2.61%)
0.1097 (17.47%)
0.1181 (1.87%)
0.1305 (11.31%)
0.1772 (22.16%)
0.1979 (35.8%)
0.2610 (1.71%)
0.3077 (10.05%)
169
Decay product : Tm
1. Target purity : Ytterbium-oxide, analytical grade
168
2. Enrichment factor : Yb enriched up to 17.1%
3. Impurity details:
Possible chemical impurities:
Gd: 0.19%, Lu: 0.05%, Er: 0.07%, Sm: 0.05%, Ho: 0.04%,
others such as K, Na, Ca, Mg, Si, Fe, Al, Cr, Ni, Cu, Mn, Pb, Sn altogether <0.1%.
4. Isotopic composition and supplier of target material:

168 170 171 172
Yb: 17.1%, Yb: 11.3%, Yb: 22.6%, Yb: 19.0%,
173 174 176
Yb: 10.0%, Yb: 15.5%, Yb: 4.5%
Ytterbium oxide of analytical grade, supplier Technabexport, Russian Federation
Cross-section value of 2300 barn is known in case of thermal neutrons. As natural ytterbium
target contains 168Yb nuclide in 0.13% only, the use of enriched ytterbium target is necessary
in order to attain proper specific activity. On the other hand, even the enriched target may
contain 174Yb and 176Yb stable isotopes in considerable extent. Since cross-section data for
these nuclides are 69 barn and 2.85 barn, the corresponding (n,J) reactions lead to the
presence of 175Yb and 177Yb impurities, respectively. The half-life of these radionuclides
formed are 101 hours and 1.9 hours, so they can be let to decay to an acceptable level by
cooling.

J. Környei,
Department of Radiochemistry, Institute of Isotopes Co., Ltd.,
H11121, Budapest, Konkoly Thege Wt-29.33, Hungary.
238
The 169Yb radionuclides can capture further neutrons with a cross-section of 3600 barn,
169
Yb (n,J) 170Yb (stable)
which decreases the 169Yb yield by forming stable ytterbium isotope in nuclear reaction. This
consecutive reactions should be taken into consideration when specific activities are
calculated.

The flow chart of the ytterbium-169 production technology can be given as follows:
enriched 168Yb-Yb2O3 target

irradiation in nuclear research reactor
169
Yb + 175Yb + 177Yb
cooling for at least 10 days to decay radionuclidic impurities
169
Yb
opening capsule,
dissolving the target in HCl, evaporation, making solution
169
Yb-ytterbium chloride bulk solution
dilution with Ca-EDTA solution,
dispensing, sterilization
169
Yb-EDTA injection.
Reactor
Nuclear research reactors with a neutron flux of 3 × 1013 — 2 × 1014 n/cm2/s can be used.
Even higher fluxes can be used if available.Water cooling of the target within the irradiation
channel, during the whole irradiation, can be advised.
Capsule details
A quartz vial with ground quartz stopper is used. Dimensions: diameter 14 mm, height:40mm.
The proper amount of the enriched ytterbium-oxide is dissolved in 2 M nitric acid at elevated
temperature. The solution is carefully evaporated to dryness. The rest is dissolved in distilled
water and an ytterbium concentration of 4 mg/mL is adjusted. 0.25 mL of this solution is
poured into the quartz irradiation vial and evaporated to dryness in vacuum.
The quartz vial is closed with its ground quartz stopper. The stopper is firmed to the vial with
aluminium wire.
The quartz vial contains 1.0 mg of ytterbium i.e. 1.14 mg Yb2O3
239
The stoppered quartz vial is encapsulated into an aluminium container possessing diameter of
30 mm, height of 110 mm. The container is closed by welding. A lifting head, for handling
the container in the irradiation channel supplied with a screw is fixed on the top of the
container. Fluxes up to 2 × 1014 n/cm2/s or even higher can be used.
100–288 hours irradiation can be performed. Irradiation on higher fluxes makes possible the
decrease of the irradiation time.
After irradiation, a cooling period of at least 30 days is required so that the 177Yb content
should completely decay and the 175Yb content should decay to an acceptable level.
Specific activity achieved and typical production yield/capsule
fluxes, 3 × 1013 1 × 1014 2 × 1014

n/cm2/s
irradiation time, h 100 288 100 288 100 288
mass of target, mg 1.14
ytterbium, mg 1.00
calculated 169Yb 1.6 4.23 5.31 14,1 10.63 28.21
yields *),
GBq
175
Yb impurity, 0.0045 0.008 0.015 0.026 0.030 0.052
GBq
175
Yb impurity, 0.28 0.18 0.28 0.18 0.28 0.18
%
*) Since yields are calculated for 1.00 mg ytterbium, the data in GBq give directly the specific activity in
GBq/mg, as well.]

For ytterbium-169 production one hot cell under negative pressure with 2 manipulators, as
well as air ventilation system with filter is required. Hot cells are made of iron with a lead
shielding of 15 –20 cm. The window of the hot cell is made of lead glass with a thickness of
25 cm. Any other conditions (e.g. radiation protection system, etc.) should correspond to the
regulations being valid for isotope laboratories of level "A".
Analysis of raw materials, reagents and chemicals required for procesing

1. Enriched ytterbium oxide target: see the specifications above.
No other analysis than trial irradiation and the determination of the radionuclidic as well
as radiochemical and chemical purity of the 169Yb obtained are suggested.
2. Nitric acid. Assay: 64–66% which corresponds to cca. 14.4 M solution. Other
impurities: chloride <5 × 10-3%, sulphate <1 × 10-3%, Cd, Co, Cu, Fe, Ni, Pb, Zn <5 ×
10-4%. (Fluka).
3. Hydrochloric acid. Assay: >36.5%.
240
Impurities: sulphate <5 × 10-4%, Fe, Zn <5 × 10-5%,
As, Cd, Co, Cr, Cu, Mn, Ni, Pb <5 × 10-6% (Fluka).
4. Ca-EDTA (Ethylenediamine-tetraacetic acid calcium disodium salt). Assay: >97%.

(Riedl de Haen). Water content measured by Karl Fisher reagent <13%. pH = 6.5–8.5
Free EDTA< 1%, As< 3 × 10-4%, lead and heavy metals < 2 × 10-3%.
5. Sodium chloride. Assay>99%, sodium and chloride content measured by flame

photometry and precipitating with barium chloride, respectively. No insoluble or
coloured materials are present. Heavy metals < 10 µg/g, arsene < 1 µg/g.

The irradiated container is delivered to the hot cell in lead container providing adequate
protection against radiation. The container is opened by mechanical cutting. The quartz vial
containing the irradiated ytterbium oxide is opened and 1 mL 1 M HCl is added to it. The
solution will be ready when is heated until boiling. The solution is poured into a glass of
50 mL and the quartz vial is rinsed with double distilled water. The solution is carefully
evaporated to a volume of cca. 0.1 mL and taken up in 10 mL double distilled water. pH
should be in the range of 2–4. Activity of 1.0 mL of the bulk ytterbium chloride solution is
measured for the calculation of specific activity and radioactive concentration.
Preparation of 169Yb-EDTA is performed by diluting the bulk solution with the mixture of 5%
Ca-EDTA and 95% NaCl solutions to the proper radioactive concentration. The final solution
is filtered on G4 filter.
Dispensing
The final 169Yb-EDTA solution is dispensed into vials by pipetting, the vials are closed with
rubber stoppers and aluminium caps. Vials are autoclaved for 30 minutes at a temperature of
120 oC for sterilization.
A vial containing 5–10 MBq I-125 sample is measured. Main gamma-peak of 169Yb are: 63.1
keV, 109.7 keV, 130.5 keV, 177.2 keV, 197.9 keV and 307.7 keV.
Impurity limits: not more than 0,4% of 175Yb (gamma of 283 keV and 396 keV, beta: 70 keV,
470 keV).
A gamma-spectrum of Ytterbium-169 can be seen in Fig. 1.
The examined sample (volume 5–15 µl) is dropped onto a chromatographic paper stripe, type
Whatman No.3, dimensions of 40 × 3 cm. The chromatogram is developed in the following
eluent mixture:
100 mL 0.025 M ammonium-sulphate + 50 mL acetone + 0.03 mL 25% ammonium-

hydroxide.
241
Developing time. 5 hours. Front distance: 20–22 cm.
169
Rf values: product, Yb-EDTA : Rf = 0.7–0.9
169
impurity: Yb-chloride : Rf = 0.0
As reference ytterbium-169-chloride solution should be used.
Product can be accepted if the 169Yb-content is higher than 98% even on the expiry date.
FIG. 1. Gamma Spectrum of 169Yb.

1. Physical observation: Clear, colourless, isotonic solution.
2. Radionuclide identification:
Ytterbium-169 radionuclide is identified by gamma spectrum (see above).
3. Radionuclidic purity: should be higher than, or equal to 99.3% i.e. 175Yb content should
be less than 0.4%, other impurities should be less than 0.3%.
5. Radiochemical purity:
Measured by the above detailed paper chromatographic method, it should be higher than
98%.
6. Concentration requirements
Specific activity: >1.11 GBq/mg
Radioactive concentration: 3.7–11.1 MBq/mL
Chemical content: 0.13–10 µg ytterbium/mL in EDTA complex form, 0.2–18 mg Na2Ca-
EDTA/mL.
7. Shelf life and recommended storage conditions
242
8. Special comments of waste generated
Wastes should be collected and left for decay. No special prescriptions are given, the
normal radioactive waste treatment procedures described for isotope laboratories should
be applied.
In case of careful operation low level contamination is expected. The glasses can be
washed and rinsed in distilled water. Radioactive wastes should be collected and let to
stay on a properly protected place to decay. New glasses should be used for each
production.

The technology can easily be performed. One crucial point should be emphasized: the target
should be enriched at least to the given factor (17.1%) in order to decrease the radionuclidic
impurities. If a target with higher 168Yb content is available, the use of it is advisable. As high
flux as possible should be used in order to increase specific activity.
BIBLIOGRAPHY
ALAZRAKI, N.P., HALPERN, S.E., ASHBURN, W.L., J. Nucl. Med. 14 (1973) 226.
DOGE, H., JOHANSEN, B.A., J. Nucl. Med. 18 (1977) 1202.
FIRESTONE, R.B., Table of Isotopes, CD ROM Edition (SHIRLEY, V.S., CHU S.Y., Eds.),
Office of High Energy and Nuclear Physics, US Department of Energy, Version 1.0 (1996).
GRYCHOWSKY, P.I., MIKULSKI, J., PETRINA, T., Obtaining and separation of 169Yb for
nuclear medicine, Radiochem. Radioanal. Letters 40(6) (1979) 373.
HETHERINGTON, E.L.R., WOOD, N.R., Production of 169Yb radiography sources in a high
flux reactor, AAEC/E, Australia 306 (1974) 22.
243
Yttrium-90 (90Y39)
Half-life : 64.0 ± 0.21 h

89
Production scheme : Y (n,J) 90Y V = 1.28 b
E
235
U (n,f) 90Sr o 90Y
Type of decay and energy : E (MeV) 2.28 (100%) Emax
Production process
Yttrium-90 is an important pure beta-emitting radioisotope of interest for therapeutic
applications in medicine as a result of the emission of a beta particle with a high maximal
energy of 2.3 MeV. Yttrium-90 is formed by decay of fission-produced strontium-90 and is
normally batch extracted from an inventory of the long-lived strontium-90 parent. In addition,
several strontium-90/yttrium-90 generators have been described, such as the chromatographic
system using Dowex 50 cation exchange system eluted with 0.003M ethylenediammine-
tetraacetic acid (EDTA) for routine in-house use (Chinol, et al., 1987). The procedure
described in this report is the process which was developed at ORNL, involving batch
extraction of yttrium-90 from fission-produced strontium-90 using di-(2-eththylhexyl)
phosphoric acid (HDEHP) extraction method.
Although batch-extracted yttrium-90 is available from several sources, the principal source in
recent years has been the U.S. Department of Energy facilities in the U.S., initially at the Oak
Ridge National Laboratory (ORNL) in Oak Ridge, Tennessee (Wike, et al., 1990), and more
recently from about 1991 to 1998, from the Pacific Norwest National Laboratory (PNNL), in
Hanford, Washington. Since 1998, the technology from PNNL was privatized by an
agreement with NEN Life Sciences, in North Billerica, Massachusetts, and yttrium-90 is now
commercially available from this source.

The radioactive strontium-90 parent material is available from purification from uranium
fission products. Yttrium-90 can also be produced by radiative (n,J) neutron capture by stable
89
Y targets (100% abundance).

Strontium-90 is one of the major products obtained from uranium fission in a nuclear reactor.

Dependent upon the levels handled, a shielded hot cell is not normally required for processing
yttrium-90 from strontium-90, and an adequately shielded glove box can be used. Since the
+3
presence of metallic (M ) impurities is more of a concern than radiation exposure, very high
purity water, reagents and equipment free of metal impurities must be used.

244
The processing procedure (Figure 1) described here is summarized from the procedure which
had been used at ORNL for many years which was described by Wike, et al. (1990).
Separation and purification of 90Y
1. The HDEHP-dodecane stock reagent is prepared for use by first stripping three times with
equal volumes of 6 M HCl to reduce trace elements and then washing with 0.1 M HCl to
reduce the acid content. Filtration through Whatman No. 1 filter paper is necessary to
remove suspended water droplets from the HDEHP-dodecane phase.
2. Strontium-90 cows up to 20 Ci* of 90SrCl2 are diluted to 50 mL with 0.1 M HCl. New
glassware, which has been acid washed, is required for each step in the separation
procedure.
3. The 90Sr cow is transferred to a 125-mL separatory funnel that contains 25 mL of 1.0 M
HDEHP in dodecane. The phases are mixed by agitation for 5 minutes and allowed to
separate.
4. The aqueous phase cow is drained into a 140-mL beaker and the 90Y-rich organic phase is
washed four times with 25 mL of 0.1 M HCl to strip the residual 90Sr. The first 25-mL
wash is added to the cow to recover 90Sr. Approximately 95% of the 90Y is back-extracted
from the organic phase by shaking it with two 25-mL vol of 6 M HCl for 5 minutes each.
5. The 6 M HCl is evaporated to moist dryness, cooled, and transferred to a second 125-mL
funnel with 25 mL of 1.0 M HDEHP-dodecane followed by a 50-mL rinse with 0.1 M
HCl.
6. A second 5-minute extraction is made, followed by four 0.1 M HCl washes that are
discharged to waste.
7. The 90Y is stripped with two 5-minute contacts with 30 mL each of 9 M HCl. The strip
solutions are combined and mixed in preparation for trace-element removal by ion-
exchange chromatography.
8. AG-1X8 (50-100 mesh) anion-exchange resin in the hydrogen form is placed in a 0.7-cm-
dia glass column to a depth of 12 cm. The column is alternately washed with 50 mL of 9
M HCl and 0.1 M HCl.
9. The 90Y-rich 9 M HCl strip solution is then passed through the anion-exchange resin at the
rate of 2 mL/minute. Finally, the column is washed with 5 mL of 9 M HCl to clean out
any residual 90Y solution.
10. The column effluent, which contains the 90Y, is again evaporated to moist dryness to
prepare for cation-exchange chromatography to remove phosphates and traces of organic
residue remaining after the previous treatment in the anion-exchange column.
11. The cation-exchange column is prepared by placing AG-50X8 (50–100 mesh) cation-
exchange resin in a 0.7-cm-dia glass column to a depth of 5 cm. The resin is conditioned
successively with 50 mL of 6 M HCl and 50 mL of 0.1 M HCl. The 90Y product from the
anion-exchange step is dissolved and transferred to the column with 50 mL of 0.1 M HCl.
245
The column flow rate is set at 2 mL/min. The 90Y adsorbed near the top of the resin is
removed from the column with 60 mL HCl, and the resulting solution is evaporated to
near dryness.
12. The yttrium product is then diluted to the desired volume and normality. The 90Sr cow
must be prepared for the subsequent separation by oxidizing soluble organic phosphates
with 5 mL of aqua regia. The residue is redissolved in 50 mL of 0.1 M HCl and stored for
the next separation.
13. Quality control and analytical procedures must be conducted rapidly and efficiently
because of the short half-life of 90Y. In addition, the 90Sr level must be accurately
determined because of the possible therapeutic application in humans. The intense E
radiation from the 90Y product solution must be reduced (by coprecipitation of the 90Y on
iron hydroxide) so that radiochemical analyses for the 90Sr in the 90Y product can be
performed in a laboratory hood. Most of the 90Y is precipitated with the iron when made
basic with NH4OH. Samples are prepared for 90Sr analyses by pipeting 1 mL of a 1000-
fold dilution into a beaker containing 10 mL of distilled water, 10 mg of Fe3+, and 25 mg
of standardized natural strontium carrier. Then the filtrate is analysed for 90Sr by routine
radiochemical methods (Krieger, 1980) following the removal of the 90Y.
FIG. 1. Processing scheme for obtaining carrier-free yttrium-90 from the strontium-90 stock
solution by solvent extraction.
246
As indicated earlier, high purity water, reagents and equipment must be used which are free of
metallic impurities, especially iron. The yttrium-90 is carrier-free, and is usually dispensed as
the chloride in dilute (0.05–0.1) HCl solution.

The product is assayed by beta counting and for the absence of metal impurities.

The radiochemical purity of yttrium-90 free of the strontium-90 parent is usually not a
problem and can be assessed by beta counting. The chemical purity of yttium-90 free of any
contaminating metal impurities is very important, however, since the chelation of yttrium-90
to many organ-specific therapeutic agents such as antibodies and peptides requires very high
specific activity with no competing metallic impurities which may compete with the limited
chelation sites. Very high purity water, reagent solutions and equipment which is free of
metallic impurities, especially iron, must therefore be used at all steps in the purification
process.
BIBLIOGRAPHY
CHINOL, M., HNATOWICH, D.J., “Generator-produced Yttrium-90 for Radioimmuno-
therapy”, J. Nucl. Med., 28 (1987) 1465–1470.
WIKE, J.S., GUYER, C.E., RAMEY, D.W., PHILLIPS, B.P., “Chemistry for Commercial
Scale Production of Yttrium-90 for Medical Research”, Appl. Radiat. Isot., 41 (1990) 861–
865.
247
Xenon-133 (133Xe54)
Half-life : 5.243 ± 0.001 d
235
Production scheme : U (n,J) 133Xe
Type of decay and energy : E (MeV) 0.3464 (95%)
Production process
Xenon-133 is formed according to 235U (n,f) reaction among the other fission products when
uranium-235 contained targets are irradiated by thermal neutrons. Xenon-133 is a gas. Then it
is purified from iodine radioactive isotopes and other volatile elements. Fission fragments
yield is 6.7%. The isotope activity per 1 g uranium-235 is ~370–445 GBq (10–12 Ci) (after
six days in irradiation and one day storage).
Target manufacturing
Reactor irradiation
Target dissolution
Gas phase trapping into Solution for 99Mo recovery

evacuated vial
Xenon-133 sorption on carbon at

liquid nitrogen temperature
Xenon-133 desorption, collection,

analysis and packing
Radiopharmaceutical production
The processing flowsheet includes the following operations:

Uranium-235 (90% enrichment) as uranium oxide pressed with magnesium oxide into a
bushing is a raw material for the xenon-133 production. The bushing is put into the annular
gap of the jackets made of stainless steel, filled with magnesium and welded. The uranium

V.V. Kanygin, E. Ya. Smetanin,
Department of Research Reactors, Isotopes and Radiopharmaceuticals,
Institute of Physics and Power Engineering, Obninsk, Russian Federation.
248
quantity per 1 target is 4.2 g. Uranium-235 of 90% enrichment produced in the Russian
Federation is used.
Irradiation parameters, specific activity and full yield at the EOI

The target is irradiated in the research reactor “AM” during 6 days in thermal neutron flux 3 ×
1013 n/cm2/s. Then the ampoule is stored during 4–6 hours for radioactive short-lived isotopes
decay.
The main requirement to the target is the uranium uniform distribution in the target
composition, tightness, and heat removal possibility during the irradiation.
The irradiation is performed in a water cooling channel. Isotope Xe-133 carrier free is formed
during the irradiation process. (specific activity is 1.4 PBq (3.8 × 104 Ci)/g. Xenon- 133 yield
per 1 target is 1.6–1.8 TBq (45–50 Ci).
TABLE I. IMPURITIES PERCENTAGE IN THE RAW MATERIAL
Impurities Percentage in uranium

Mo 2.5 × 10-3
Fe 2.5 × 10-3
Mn 3.0 × 10-4
Bu <2.0 × 10-3
Cu 1.1 × 10-4
Al 3.0 × 10-3
Cd <3.0 × 10-5
Ti <1.0 × 10-4
Cr <2.5 × 10-3
Pb 10-3

The main process operation is the ampoule dissolution. It is performed in the “hot” cell
having the sufficient biological shield and the infrastructure appropriate for the isotope
production (special ventilation, special sewerage, zonal layout of premises).
The processing is continued in the protective scaled box, the product is transferred through
the process lines.
The pressure drop between the operator's and working premises must not be less than 20 mm
of water column in case of the “hot” cell and protective box.
Taking into account the physical state (gas) all the process equipment and process lines have
to ensure the tightness.
Analysis of raw material, reagents and chemicals required for processing

As it is described in the section II (the target preparation) 90% enriched uranium is used as
the raw material. The input control of uranium dioxide batches and the ampoule composition
materials (MgO, Mg) is carried out.
The reagents — activate carbon, ethyl alcohol, distilled water, acetone — are of the best
marks (X4, RGA), and the input control confirms their correspondence to the given
specification.
249
After the irradiation the ampoule is transported from the reactor facility to the “hot”
laboratory building. The ampoule is cut to pieces of 400 mm in the “hot” cell, and these
pieces are dissolved in nitric acid (8M).
During the cutting and dissolution the exhaust goes through aerosol and radioactive iodine
trapping system (two scrubbers with 4M alkali + silica gel columns) and is collected in a tank
of 50 liters volume. Then it is sorbed on carbon column by cryogen method.
The sorption column is transported to a heavy box where it is connected to the gas collector
with the help of the reentrant line. A heater is put inside the sorption column, and the column
heating is turned on.
The heating is controlled with the help of a thermocouple put into the sorption column, and
also — by water coming into a receiving tank of the gas collector according to the measuring
line.
When the gas collector is filled 90%, the heating is turned off. The gas sample is taken to an
evacuated vial through the pre-packing device transferring line.
Xenon-133 content is measured approximately in a gas sample. If the gas concentration

activity is not a satisfactory one, the gas from the gas collector is transferred to a tank through
the reentrant line for xenon utilization. And the column annealing is repeated.
If the gas concentration activity is a satisfactory one, the gas from the gas collector is
transferred by accurately measured portions to the pre-packing box through the transfer line.
The pre-packing device electromagnetic valves control the solution volume being transferred.
In the xenon pre-packing device the gas is transferred to an evacuated vial through the valve
system and the needle.
The vial is put into KT-1-5 transport container and sent for the activity measurement.

A batch of the preparation which is extracted and collected into the gas collector (see the
processing flowsheet) is the final product. A sample is taken from this batch to an injection
vial for measurements of total activity, activity concentration and radionuclide impurity
contents. The activity and radionuclide impurity content values are determined by means of
the gamma-spectrometric method.
The measurement equipment is a semi-conducting gamma-spectrometer which includes the

following units:
– detector of DGDK-63 type placed into evacuated cryostat and being cooled up to the
temperature of –160oC;
– pre-amplifier of BUS-2-96 type or PUG-P-01 type;
– multi-channel pulse analyser of Al-1024-95M type;
– information processing and management unit on the base of PC “ES-1841”;
– gamma-spectrum processing code “Balbi-S”.
250
Auxiliary equipment:
– set of standard spectrometric gamma-sources;
– reference volumetric radiation source containing radionuclide Ba-133 which is calibrated
with an error of ±5%;
– the detector lead shield of 5Onim thickness;
– KT-5 lead container with a collimator on the bottom.
The same equipment is used to measure the radionuclide impurities simultaneously with the
sample activity measurement. The radionuclide impurity detection sensitivity is not less than
0.05% of the basic isotope activity.
The product quality control also includes:
– visual inspection (transparent, colourless gas);
– capsule or vial scaling control.
This operation is carried out by the method of xenon-133 activity measurement repeated in 12
hours. The vial is considered sealed if a result of the xenon activity repeated measurement
differs from the first measurement result within the confident boundaries of the measurement
result total error taking into account a correction for radionuclide xenon-133 decay.
The ampoule or vial surface contamination level is determined by taking a smear and by
measuring its activity.

Chemical form, appearance: transparent, colourless gas.
Specific activity, Ci/g: >1000.
Concentration activity, Ci/mL
Content of radionuclide impurities,% of xenon- 13 3 activity:
131m
Xe – 1.5
135m
Xe – 1.0
85
Kr – 0.5
Shelf life is up to l0 days.

The xenon-133 production technology is a part of Mo-99 recovery technology from irradiated
uranium target. 131I (fission), 95Zr, and 140Ba are also recovered from the same target.
The 133Xe production technology provides its regular (weekly) production and stable quality
parameters. This preparation is supplied to radiopharmaceutical companies for
radiopharmaceuticals production.
In particular, the stable routine production of two radiopharmaceuticals is organized on the

basis of 133Xe production cycle:
– xenon-133 in isotonic solution;
– air-xenon mixture.
251
CONTRIBUTORS TO DRAFTING AND REVIEW
Akaboshi, M. Research Reactor Institute, Kyoto University, Japan
Alberto, R. Paul Scherrer Institute, Switzerland
Ananthakrishnan, M. Board of Radiation and Isotope Technology, India
Aungurarat, G. Office of Atomic Energy for Peace, Thailand
Beets, A.L. Oak Ridge National Laboratory, United States of America
Bhagwat, A.M. Bhabha Atomic Research Center, India
Brihaye, C. Cyclotron Research Centre, Belgium
Callahan, A.P. Oak Ridge National Laboratory, United States of America
Cheng Zuoyong Nuclear Power Institute of China, China
De Villiers, W. van Z. South African Nuclear Energy Corporation Ltd., South Africa
Du, M. Oak Ridge National Laboratory, United States of America
Hanafiah Ws., A. National Atomic Energy Agency, Indonesia
Iyer, S.R.K. Board of Radiation and Isotope Technology, India
Jauhri, G.S. Bhabha Atomic Research Center, India
Jiang Bingsheng Nuclear Power Institute of China, China
Jin Xiao Lai Department of Isotope, CIAE, China
Kanygin, V.V. Institute of Physics and Power Engineering, Obninsk,

Russian Federation
Knapp, F.F., Jr. Oak Ridge National Laboratory, United States of America
Környei, J. Institute of Isotopes Co. Ltd, Hungary
Kyung Bae Park Hanaro Centre, KAERI, Republic of Korea
Lambrecht, R.M. University of Tübingen, Germany
Li Maoliang Nuclear Power Institute of China, China
Li Wen Massachusetts Institute of Technology,

Cambridge, United States of America
Manzini, A. Ezeiza Atomic Centre, CNEA, Argentina
Mausner, L.F. Brookhaven National Laboratory, United States of America
253
Mirzadeh, S. Oak Ridge National Laboratory, United States of America
Narasimhan, D.V.S. International Atomic Energy Agency
Novak, K. POLATOM, Poland
Panek Finda, H. Mallinckrodt Medical B.V., Netherlands
Ponsard, B. CEN.SCK, Belgium
Sangurdekar, P.R. Bhabha Atomic Research Center, India
Sankaranarayanan, S. Bhabha Atomic Research Center, India
Schubiger, P.A. Paul Scherrer Institute, Switzerland
Schwerer, O. International Atomic Energy Agency
Smetanin, E.Y. Institute of Physics and Power Engineering, Obninsk,

Russian Federation
Srivenkatesan, R. Bhabha Atomic Research Center, India
Subramanian,V.G.R. Board of Radiation and Isotope Technology, India
Takahashi, H. Japan Atomic Energy Research Institute, Japan
Vera Ruiz, H. International Atomic Energy Agency
254

Manual For Reactor Produced Radioisotopes: IAEA-TECDOC-1340

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IAEA-TECDOC-1340

MANUAL FOR REACTOR PRODUCED RADIOISOTOPES

Radioisotopes find extensive applications in several fields including medicine, industry,

1. PRINCIPLES OF PRODUCTION, PROCESSING AND HANDLING

2. PRODUCTION AND PROCESSING METHODS FOR

Radioisotopes find wide-ranging applications in various fields, including industry,

1.2. Research reactors for isotope production

1.3. Nuclear reactions

The pile neutrons are classified according to their energy as follows:

1.3.1.1. Thermal neutrons

1.3.1.2. Epithermal neutrons

1.3.1.3. Fast neutrons

At very high neutron energies, the cross-section value decreases sharply.

1.3.3. Types of nuclear reactions

1.3.3.2. (n, J) oE  reaction

1.3.3.3. (n, p) reaction

In some cases the absorption of neutron leads to emission of a proton as outgoing

1.3.3.4. (n,D) reaction

High specific activity/carrier free products could also be obtained in this.

1.3.3.5. Multistage reactions

Thermal neutron induced fission of uranium-235 provides a host of useful radioisotopes.

1.4. Calculation of radioisotope yield

ON’ indicates the decay rate of product nucleus.

V is the neutron activation cross-section leading to the production of radioisotope of

When t » T½, we get saturation activity

Equation 3 clearly shows that growth of activity in a target under irradiation is

1.4.1. Corrections to the activation equation

– self shielding effect in the target

1.4.2. Self-shielding effect

6a´ is the microscopic absorption cross-section.

FIG. 1-3. Self-shielding factor for slab and sphere.

1.4.3. Power variation in the reactors

It is difficult to theoretically evaluate the effect of power variation on the activity

Equation 6 can be solved to obtain specific activity S, as follows:

1.4.5. Irradiation efficiency

1.5. Irradiation techniques

1.5.1. Choice of target material

1.5.2. Target encapsulation

Target materials should be properly encapsulated in suitable containers before

– physical form of target (solid, liquid or gas)

– Absorption cross-section is low (aluminium is considered as nearly transparent to

1.5.3. Safety evaluation of in-pile irradiation and experimental assemblies

It is required to thoroughly evaluate a target material or an assembly to be introduced in

1.6. Laboratory facilities for radioisotope production

During irradiation of target a number of radionuclides of different half-lives and

It will be ideal to locate such a radioisotope processing facility in the vicinity of a

1.6.1. Layout and basic infrastructure

Since a radioisotope production facility will be handling radioisotopes with different

Utility services at the laboratory can include:

– hot and cold water

The flooring of such radiochemical laboratories is preferably covered with replaceable

1.6.2. Radiological protection

In a permanent facility, acceptable levels of radiation are achieved by providing fixed

Inhalation is a possible way of intake by workers of airborne radioactive materials.

1.6.3. Radioisotope handling facilities

FIG. 1-5. Fume hood for handling radioisotopes.

(2) Glove boxes

(3) Shielded tong boxes

FIG. 1-7. Shielded tong boxes for processing of radioisotopes.

1.3.3.2. (n, J) oE reaction

Type of decay and energy : E (MeV) 0.257 (Emax) (100%)

Type of decay and energy : E (keV) 156.478 ± 0.009