... Except for men with bachelor's degrees (who earn more than those with master&... more ... Except for men with bachelor's degrees (who earn more than those with master's), salary increases with educational degrees and with academic rank. The fine arts department has signifi-cantly lower, and the medical school sig-nificantly higher, salaries than the rest of the ...
This research investigated how an individual's endorsements of mitigation and adaptation rela... more This research investigated how an individual's endorsements of mitigation and adaptation relate to each other, and how well each of these can be accounted for by relevant social psychological factors. Based on survey data from two European convenience samples (N = 616 / 309) we found that public endorsements of mitigation and adaptation are strongly associated: Someone who is willing to reduce greenhouse gas emissions (mitigation) is also willing to prepare for climate change impacts (adaptation). Moreover, people endorsed the two response strategies for similar reasons: People who believe that climate change is real and dangerous, who have positive attitudes about protecting the environment and the climate, and who perceive climate change as a risk, are willing to respond to climate change. Furthermore, distinguishing between (spatially) proximal and distant risk perceptions suggested that the idea of portraying climate change as a proximal (i.e., local) threat might indeed be ...
(+)-1'-[4-Hydroxy-1-(4-fluorobenzyl)piperidin-3-yl]spiro[1H- indene-1,4'- piperid... more (+)-1'-[4-Hydroxy-1-(4-fluorobenzyl)piperidin-3-yl]spiro[1H- indene-1,4'- piperidine] {(+)-Spiro-FBT}, a high-affinity vesicular acetylcholine transporter ligand, was labeled with fluorine-18, and evaluated in the rat and monkey. In the rat brain, (+)-[18F]Spiro-FBT accumulated preferentially in the striatum, hippocampus, and cortex, brains regions containing high-to-moderate densities of cholinergic terminals. However, due to rapid metabolism, no preferential accumulation of the radiotracer was observed in corresponding regions of the monkey brain. Consequently, rapid metabolism renders (+)-[18F]Spiro-FBT unsuitable for studying cholinergic function with positron emission tomography.
International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology, 1992
The use of internal-surface reversed-phase (ISRP) chromatography of unprocessed plasma samples wa... more The use of internal-surface reversed-phase (ISRP) chromatography of unprocessed plasma samples was investigated as an alternative method of quantitation of the arterial plasma metabolite time course of [18F]N-methylspiperone. The ISRP method was directly compared to standard solid phase extraction/HPLC (SPE/HPLC) methods currently in wide use. Results indicate that: (1) the ISRP method is rapid and minimizes sample preparation; (2) recovery of radioactivity from the ISRP column is greater than 90%; (3) no radioactivity remains associated with chromatographically size excluded proteins and (4) the quantitative results are well correlated with conventional SPE/HPLC methods.
Labial minor gland salivary flow rate and sodium concentration were analyzed in relation to 1) hi... more Labial minor gland salivary flow rate and sodium concentration were analyzed in relation to 1) histologic findings in labial biopsy specimens and 2) the occurrence of chronic graft-versus-host disease (GVHD) in patients who received bone marrow transplants. Biopsy specimens and samples were obtained from 61 recipients of marrow transplants (including three twins) 51 to 1,260 days post transplantation. Labial saliva sodium concentrations were elevated in some patients, and these increases were associated with inflammation and destruction of minor salivary gland acini and ducts by chronic GVHD or other factors. The predictive value of the salivary sodium changes in evaluating labial salivary gland pathologic changes was 91 per cent, and the sensitivity was 74 per cent. Thus, if a transplant recipient is found to have an elevated labial saliva sodium level, then the probability that he has pathologic labial gland changes is 91 per cent. When analyses were restricted to include only patients who received no irradiation during transplantation, then elevated labial saliva sodium concentration was significantly associated with the occurrence of chronic GVHD. The sensitivity of this relationship was 42 per cent, but the predictive value was 100 per cent. Thus, if a nonirradiated transplant recipient is found to have an elevated labial saliva sodium concentration, then it is virtually certain that he has chronic GVHD. We found no significant changes in labial saliva flow rates in these bone marrow transplant recipients.
Page 1. 2004 IEEE Aerospace Conference Proceedings Pattern Synthesis of Conformal Arrays for Airb... more Page 1. 2004 IEEE Aerospace Conference Proceedings Pattern Synthesis of Conformal Arrays for Airborne Vehicles12 Thomas E. Morton United States Air Force Research Laboratory 2241 Avionics Circle Wright-Patterson ...
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Jan 29, 2015
The 2005 National Institute of Health (NIH) Consensus Conference outlined histopathological diagn... more The 2005 National Institute of Health (NIH) Consensus Conference outlined histopathological diagnostic criteria for the major organ systems affected by both acute and chronic graft-versus-host disease (GVHD). The 2014 Consensus Conference led to this updated document with new information from histopathological studies of GVHD in the gut, liver, skin and oral mucosa and expanded discussion of GVHD in the lungs and kidneys. The recommendations for final histological diagnostic categories have been simplified from 4 categories to 3: no GVHD, possible, and likely GVHD based on better reproducibility achieved by combining the previous categories of consistent with and definite GVHD into the single category of likely GVHD. Issues remain in the histopathological characterization of GVHD, particularly with respect to the threshold of histological changes required for diagnostic certainty. Guidance is provided for the incorporation of biopsy information into prospective clinical studies of G...
Medical Imaging 2010: Physics of Medical Imaging, 2010
This paper describes the image quality improvements achieved by developing a new fully physical i... more This paper describes the image quality improvements achieved by developing a new fully physical imaging chain. The key enablers for this imaging chain are a new scatter correction technique and an analytic computation of the beam hardening correction for each detector. The new scatter correction technique uses off-line Monte Carlo simulations to compute a large database of scatter kernels representative
To assess lesion detection and image quality parameters of a knowledge-based Iterative Model Reco... more To assess lesion detection and image quality parameters of a knowledge-based Iterative Model Reconstruction (IMR) in reduced dose (RD) abdominal CT examinations. This IRB-approved prospective study included 82 abdominal CT examinations performed for 41 consecutive patients (mean age, 62 ± 12 years; F:M 28:13) who underwent a RD CT (SSDE, 1.5 mGy ± 0.4 [∼ 0.9 mSv] at 120 kV with 17-20 mAs/slice) immediately after their standard dose (SD) CT exam (10 mGy ± 3 [∼ 6 mSv] at 120 kV with automatic exposure control) on 256 MDCT (iCT, Philips Healthcare). SD data were reconstructed using filtered back projection (FBP). RD data were reconstructed with FBP and IMR. Four radiologists used a five-point scale (1=image quality better than SD CT to 5=image quality unacceptable) to assess both subjective image quality and artifacts. Lesions were first detected on RD FBP images. RD IMR and RD FBP images were then compared side-by-side to SD-FBP images in an independent, randomized and blinded fashion. Friedman's test and intraclass correlation coefficient were used for data analysis. Objective measurements included image noise and attenuation as well as noise spectral density (NSD) curves to assess the noise in frequency domain were obtained. In addition, a low-contrast phantom study was performed. All true lesions (ranging from 32 to 55) on SD FBP images were detected on RD IMR images across all patients. RD FBP images were unacceptable for subjective image quality. Subjective ratings showed acceptable image quality for IMR for organ margins, soft-tissue structures, and retroperitoneal lymphadenopathy, compared to RD FBP in patients with a BMI ≤ 25 kg/m(2) (median-range, 2-3). Irrespective of patient BMI, subjective ratings for hepatic/renal cysts, stones and colonic diverticula were significantly better with RD IMR images (P<0.01). Objective image noise for RD FBP was 57-66% higher, and for RD IMR was 8-56% lower than that for SD-FBP…
1. Trends Biochem Sci. 1998 Apr;23(4):149-50. CLAMP: a biosensor kinetic data analysis program. M... more 1. Trends Biochem Sci. 1998 Apr;23(4):149-50. CLAMP: a biosensor kinetic data analysis program. Myszka DG, Morton TA. Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City 84112-5330, USA. [email protected]. ...
Whole saliva samples and lip biopsies were collected from 12 allogeneic bone marrow transplant re... more Whole saliva samples and lip biopsies were collected from 12 allogeneic bone marrow transplant recipients who developed extensive chronic graft-versus-host disease (GVHD) and from 10 healthy allogeneic and syngeneic recipients without GVHD. Six of ten biopsies from patients with chronic GVHD had lichenoid stomatitis or sialadenitis, or both, with sialodochitis. Seven of nine biopsies from patients free of chronic GVHD were entirely normal, and two had either mild glandular or mucosal changes. Salivary gland involvement in chronic GVHD was associated with decreased or absent levels of salivary IgA and inorganic phosphate, decreased salivary flow rates, and increased concentrations of salivary sodium, albumin, and IgG. The most striking abnormalities were found in patients with histologic evidence of sialadenitis. In contrast, marrow transplant recipients without chronic GVHD had normal salivary immunoglobulin and electrolyte levels. Secretory IgA deficiency may contribute to the frequent sinobronchial infections observed in patients with chronic GVHD.
Interactions of organic compounds with polar lipid monolayers have been widely studied and fall i... more Interactions of organic compounds with polar lipid monolayers have been widely studied and fall into two general categories: polar molecules (often electrically charged), which interact primarily with head groups, and non-polar molecules, which interact with tail groups. This study presents results for a typical odorant molecule, cyclohexanone, which is semipolar in the sense that the dipolar functional group (a carbonyl) is part of a small, non-polar hydrocarbon ring. Thermodynamic measurements on monolayers prepared from pure L-Qtdipalmitoyllecithin (DPPC) reveal effects from cyclohexanone in the subphase on the AG for compression, which exhibits a maximum as a function of temperature, suggesting that interaction of the cyclohexane ring with hydrophobic tail groups dominates below 297 K, while interaction of the carbonyl function with head groups dominates above 297 K. Measurements of the surface dipole moment confirm this inference: when cyclohexanone is in the subphase the surface dipole moment is less than the value of # for pure DPPC when the temperature is below 297 K. Above 297 K the surface dipole moment in the presence of cyclohexanone has a value greater than or equal to St for pure DPPC. Variations in orientation of small molecules within lipid assemblies might conceivably contribute to membrane recognition of an odorant.
... Masashi Yamaguchi, Scott V. Serafin, Thomas Hellman Morton, and Eric L. Chronister*. Departme... more ... Masashi Yamaguchi, Scott V. Serafin, Thomas Hellman Morton, and Eric L. Chronister*. Department of Chemistry, University of California, Riverside, California 92521-0408. J. Phys. Chem. ... In the solid phase, the fully extended (AAAA) conformation is considered dominant. ...
The purpose of the present set of studies was to characterize, in vitro and in vivo, two benzamid... more The purpose of the present set of studies was to characterize, in vitro and in vivo, two benzamide analogues, 2,3-dimethoxy-N-[l-(4-fluorobenzyl)piperidin-4yllbenzamide (MBP) and 4'-fluoroclebopride (FCP), for studying dopamine D2 receptors with Positron Emission Tomography (PET). In vitro binding studies were conducted to determine the affinities of MBP and FCP to the three subtypes of dopamine D2 receptors: D2(iong,, D,?, and D, receptors. MBP was found to have a high affinity (K, = 1-8 nM) for all three subtypes of the D2 receptor, whereas FCP had nanomolar affinity (K, -5.5 nM)
The goal of the present set of studies was to characterize the in vitro binding properties and in... more The goal of the present set of studies was to characterize the in vitro binding properties and in vivo tissue kinetics for the vesicular acetylcholine transporter (VAcChT) radiotracer, [18F](+)-4-fluorobenzyltrozamicol ([18F](+)-FBT). In vitro binding studies were conducted in order to determine the affinity of the (+)- and (-)-stereoisomers of FBT for the VAcChT as well as sigma (sigma 1 and sigma 2) receptors. (+)-FBT was found to have a high affinity (Ki = 0.22 nM) for the VAcChT and lower affinities for sigma 1 (21.6 nM) and sigma 2 (35.9 nM) receptors, whereas (-)-FBT had similar affinities for the VAcChT and sigma 1 receptors (approximately 20 nM) and a lower affinity for sigma 2 (110 nM) receptors. PET imaging studies were conducted in rhesus monkeys (n = 3) with [18F](+)-FBT. [18F](+)-FBT was found to have a high accumulation and slow rate of washout from the basal ganglia, which is consistent with the labeling of cholinergic interneurons in this brain region. [18F](+)-FBT also displayed reversible binding kinetics during the 3 h time course of PET and produced radiolabeled metabolites that did not cross the blood-brain barrier. The results from the current in vitro and in vivo studies indicate that [18F](+)-FBT is a promising ligand for studying cholinergic terminal density, with PET, via the VAcChT.
... Kathleen A. Grant 1,2 ,; Carol A. Shively 2 ,; Michael A. Nader 1 ,; Richard L. Ehrenkaufer 3... more ... Kathleen A. Grant 1,2 ,; Carol A. Shively 2 ,; Michael A. Nader 1 ,; Richard L. Ehrenkaufer 3 ,; Scott W. Line 3 ,; Thomas E. Morton 3 ,; H. Donald ... Department of Physiology & Pharmacology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina ...
A series of brain uptake studies and PET imaging studies were conducted with the sigma(1) selecti... more A series of brain uptake studies and PET imaging studies were conducted with the sigma(1) selective imaging agent, [(18)F]FBFPA. The results of the study indicate that this radiotracer readily crosses the blood-brain barrier and labels sigma(1) receptors in vivo. In vivo blocking studies with a sigma(1) selective ligand and a nonselective sigma(1)/sigma(2) receptor ligand indicates that [(18)F]FBFPA labels sigma(1) and not sigma(2) receptors in rodent brain. PET imaging studies demonstrated a high uptake in regions of rhesus monkey brain having a high density of sigma(1) receptors. The uptake of [(18)F]FBFPA was displaced by the sigma ligand, haloperidol (1 mg/kg, i.v.). In vivo blocking studies indicate that the progesterone blocked the brain uptake of [(18)F]FBFPA in rat brain. These data indicate that [(18)F]FBFPA is a potential radiotracer for imaging sigma(1) receptors in the CNS in vivo with PET.
... Except for men with bachelor's degrees (who earn more than those with master&... more ... Except for men with bachelor's degrees (who earn more than those with master's), salary increases with educational degrees and with academic rank. The fine arts department has signifi-cantly lower, and the medical school sig-nificantly higher, salaries than the rest of the ...
This research investigated how an individual's endorsements of mitigation and adaptation rela... more This research investigated how an individual's endorsements of mitigation and adaptation relate to each other, and how well each of these can be accounted for by relevant social psychological factors. Based on survey data from two European convenience samples (N = 616 / 309) we found that public endorsements of mitigation and adaptation are strongly associated: Someone who is willing to reduce greenhouse gas emissions (mitigation) is also willing to prepare for climate change impacts (adaptation). Moreover, people endorsed the two response strategies for similar reasons: People who believe that climate change is real and dangerous, who have positive attitudes about protecting the environment and the climate, and who perceive climate change as a risk, are willing to respond to climate change. Furthermore, distinguishing between (spatially) proximal and distant risk perceptions suggested that the idea of portraying climate change as a proximal (i.e., local) threat might indeed be ...
(+)-1'-[4-Hydroxy-1-(4-fluorobenzyl)piperidin-3-yl]spiro[1H- indene-1,4'- piperid... more (+)-1'-[4-Hydroxy-1-(4-fluorobenzyl)piperidin-3-yl]spiro[1H- indene-1,4'- piperidine] {(+)-Spiro-FBT}, a high-affinity vesicular acetylcholine transporter ligand, was labeled with fluorine-18, and evaluated in the rat and monkey. In the rat brain, (+)-[18F]Spiro-FBT accumulated preferentially in the striatum, hippocampus, and cortex, brains regions containing high-to-moderate densities of cholinergic terminals. However, due to rapid metabolism, no preferential accumulation of the radiotracer was observed in corresponding regions of the monkey brain. Consequently, rapid metabolism renders (+)-[18F]Spiro-FBT unsuitable for studying cholinergic function with positron emission tomography.
International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology, 1992
The use of internal-surface reversed-phase (ISRP) chromatography of unprocessed plasma samples wa... more The use of internal-surface reversed-phase (ISRP) chromatography of unprocessed plasma samples was investigated as an alternative method of quantitation of the arterial plasma metabolite time course of [18F]N-methylspiperone. The ISRP method was directly compared to standard solid phase extraction/HPLC (SPE/HPLC) methods currently in wide use. Results indicate that: (1) the ISRP method is rapid and minimizes sample preparation; (2) recovery of radioactivity from the ISRP column is greater than 90%; (3) no radioactivity remains associated with chromatographically size excluded proteins and (4) the quantitative results are well correlated with conventional SPE/HPLC methods.
Labial minor gland salivary flow rate and sodium concentration were analyzed in relation to 1) hi... more Labial minor gland salivary flow rate and sodium concentration were analyzed in relation to 1) histologic findings in labial biopsy specimens and 2) the occurrence of chronic graft-versus-host disease (GVHD) in patients who received bone marrow transplants. Biopsy specimens and samples were obtained from 61 recipients of marrow transplants (including three twins) 51 to 1,260 days post transplantation. Labial saliva sodium concentrations were elevated in some patients, and these increases were associated with inflammation and destruction of minor salivary gland acini and ducts by chronic GVHD or other factors. The predictive value of the salivary sodium changes in evaluating labial salivary gland pathologic changes was 91 per cent, and the sensitivity was 74 per cent. Thus, if a transplant recipient is found to have an elevated labial saliva sodium level, then the probability that he has pathologic labial gland changes is 91 per cent. When analyses were restricted to include only patients who received no irradiation during transplantation, then elevated labial saliva sodium concentration was significantly associated with the occurrence of chronic GVHD. The sensitivity of this relationship was 42 per cent, but the predictive value was 100 per cent. Thus, if a nonirradiated transplant recipient is found to have an elevated labial saliva sodium concentration, then it is virtually certain that he has chronic GVHD. We found no significant changes in labial saliva flow rates in these bone marrow transplant recipients.
Page 1. 2004 IEEE Aerospace Conference Proceedings Pattern Synthesis of Conformal Arrays for Airb... more Page 1. 2004 IEEE Aerospace Conference Proceedings Pattern Synthesis of Conformal Arrays for Airborne Vehicles12 Thomas E. Morton United States Air Force Research Laboratory 2241 Avionics Circle Wright-Patterson ...
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Jan 29, 2015
The 2005 National Institute of Health (NIH) Consensus Conference outlined histopathological diagn... more The 2005 National Institute of Health (NIH) Consensus Conference outlined histopathological diagnostic criteria for the major organ systems affected by both acute and chronic graft-versus-host disease (GVHD). The 2014 Consensus Conference led to this updated document with new information from histopathological studies of GVHD in the gut, liver, skin and oral mucosa and expanded discussion of GVHD in the lungs and kidneys. The recommendations for final histological diagnostic categories have been simplified from 4 categories to 3: no GVHD, possible, and likely GVHD based on better reproducibility achieved by combining the previous categories of consistent with and definite GVHD into the single category of likely GVHD. Issues remain in the histopathological characterization of GVHD, particularly with respect to the threshold of histological changes required for diagnostic certainty. Guidance is provided for the incorporation of biopsy information into prospective clinical studies of G...
Medical Imaging 2010: Physics of Medical Imaging, 2010
This paper describes the image quality improvements achieved by developing a new fully physical i... more This paper describes the image quality improvements achieved by developing a new fully physical imaging chain. The key enablers for this imaging chain are a new scatter correction technique and an analytic computation of the beam hardening correction for each detector. The new scatter correction technique uses off-line Monte Carlo simulations to compute a large database of scatter kernels representative
To assess lesion detection and image quality parameters of a knowledge-based Iterative Model Reco... more To assess lesion detection and image quality parameters of a knowledge-based Iterative Model Reconstruction (IMR) in reduced dose (RD) abdominal CT examinations. This IRB-approved prospective study included 82 abdominal CT examinations performed for 41 consecutive patients (mean age, 62 ± 12 years; F:M 28:13) who underwent a RD CT (SSDE, 1.5 mGy ± 0.4 [∼ 0.9 mSv] at 120 kV with 17-20 mAs/slice) immediately after their standard dose (SD) CT exam (10 mGy ± 3 [∼ 6 mSv] at 120 kV with automatic exposure control) on 256 MDCT (iCT, Philips Healthcare). SD data were reconstructed using filtered back projection (FBP). RD data were reconstructed with FBP and IMR. Four radiologists used a five-point scale (1=image quality better than SD CT to 5=image quality unacceptable) to assess both subjective image quality and artifacts. Lesions were first detected on RD FBP images. RD IMR and RD FBP images were then compared side-by-side to SD-FBP images in an independent, randomized and blinded fashion. Friedman's test and intraclass correlation coefficient were used for data analysis. Objective measurements included image noise and attenuation as well as noise spectral density (NSD) curves to assess the noise in frequency domain were obtained. In addition, a low-contrast phantom study was performed. All true lesions (ranging from 32 to 55) on SD FBP images were detected on RD IMR images across all patients. RD FBP images were unacceptable for subjective image quality. Subjective ratings showed acceptable image quality for IMR for organ margins, soft-tissue structures, and retroperitoneal lymphadenopathy, compared to RD FBP in patients with a BMI ≤ 25 kg/m(2) (median-range, 2-3). Irrespective of patient BMI, subjective ratings for hepatic/renal cysts, stones and colonic diverticula were significantly better with RD IMR images (P<0.01). Objective image noise for RD FBP was 57-66% higher, and for RD IMR was 8-56% lower than that for SD-FBP…
1. Trends Biochem Sci. 1998 Apr;23(4):149-50. CLAMP: a biosensor kinetic data analysis program. M... more 1. Trends Biochem Sci. 1998 Apr;23(4):149-50. CLAMP: a biosensor kinetic data analysis program. Myszka DG, Morton TA. Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City 84112-5330, USA. [email protected]. ...
Whole saliva samples and lip biopsies were collected from 12 allogeneic bone marrow transplant re... more Whole saliva samples and lip biopsies were collected from 12 allogeneic bone marrow transplant recipients who developed extensive chronic graft-versus-host disease (GVHD) and from 10 healthy allogeneic and syngeneic recipients without GVHD. Six of ten biopsies from patients with chronic GVHD had lichenoid stomatitis or sialadenitis, or both, with sialodochitis. Seven of nine biopsies from patients free of chronic GVHD were entirely normal, and two had either mild glandular or mucosal changes. Salivary gland involvement in chronic GVHD was associated with decreased or absent levels of salivary IgA and inorganic phosphate, decreased salivary flow rates, and increased concentrations of salivary sodium, albumin, and IgG. The most striking abnormalities were found in patients with histologic evidence of sialadenitis. In contrast, marrow transplant recipients without chronic GVHD had normal salivary immunoglobulin and electrolyte levels. Secretory IgA deficiency may contribute to the frequent sinobronchial infections observed in patients with chronic GVHD.
Interactions of organic compounds with polar lipid monolayers have been widely studied and fall i... more Interactions of organic compounds with polar lipid monolayers have been widely studied and fall into two general categories: polar molecules (often electrically charged), which interact primarily with head groups, and non-polar molecules, which interact with tail groups. This study presents results for a typical odorant molecule, cyclohexanone, which is semipolar in the sense that the dipolar functional group (a carbonyl) is part of a small, non-polar hydrocarbon ring. Thermodynamic measurements on monolayers prepared from pure L-Qtdipalmitoyllecithin (DPPC) reveal effects from cyclohexanone in the subphase on the AG for compression, which exhibits a maximum as a function of temperature, suggesting that interaction of the cyclohexane ring with hydrophobic tail groups dominates below 297 K, while interaction of the carbonyl function with head groups dominates above 297 K. Measurements of the surface dipole moment confirm this inference: when cyclohexanone is in the subphase the surface dipole moment is less than the value of # for pure DPPC when the temperature is below 297 K. Above 297 K the surface dipole moment in the presence of cyclohexanone has a value greater than or equal to St for pure DPPC. Variations in orientation of small molecules within lipid assemblies might conceivably contribute to membrane recognition of an odorant.
... Masashi Yamaguchi, Scott V. Serafin, Thomas Hellman Morton, and Eric L. Chronister*. Departme... more ... Masashi Yamaguchi, Scott V. Serafin, Thomas Hellman Morton, and Eric L. Chronister*. Department of Chemistry, University of California, Riverside, California 92521-0408. J. Phys. Chem. ... In the solid phase, the fully extended (AAAA) conformation is considered dominant. ...
The purpose of the present set of studies was to characterize, in vitro and in vivo, two benzamid... more The purpose of the present set of studies was to characterize, in vitro and in vivo, two benzamide analogues, 2,3-dimethoxy-N-[l-(4-fluorobenzyl)piperidin-4yllbenzamide (MBP) and 4'-fluoroclebopride (FCP), for studying dopamine D2 receptors with Positron Emission Tomography (PET). In vitro binding studies were conducted to determine the affinities of MBP and FCP to the three subtypes of dopamine D2 receptors: D2(iong,, D,?, and D, receptors. MBP was found to have a high affinity (K, = 1-8 nM) for all three subtypes of the D2 receptor, whereas FCP had nanomolar affinity (K, -5.5 nM)
The goal of the present set of studies was to characterize the in vitro binding properties and in... more The goal of the present set of studies was to characterize the in vitro binding properties and in vivo tissue kinetics for the vesicular acetylcholine transporter (VAcChT) radiotracer, [18F](+)-4-fluorobenzyltrozamicol ([18F](+)-FBT). In vitro binding studies were conducted in order to determine the affinity of the (+)- and (-)-stereoisomers of FBT for the VAcChT as well as sigma (sigma 1 and sigma 2) receptors. (+)-FBT was found to have a high affinity (Ki = 0.22 nM) for the VAcChT and lower affinities for sigma 1 (21.6 nM) and sigma 2 (35.9 nM) receptors, whereas (-)-FBT had similar affinities for the VAcChT and sigma 1 receptors (approximately 20 nM) and a lower affinity for sigma 2 (110 nM) receptors. PET imaging studies were conducted in rhesus monkeys (n = 3) with [18F](+)-FBT. [18F](+)-FBT was found to have a high accumulation and slow rate of washout from the basal ganglia, which is consistent with the labeling of cholinergic interneurons in this brain region. [18F](+)-FBT also displayed reversible binding kinetics during the 3 h time course of PET and produced radiolabeled metabolites that did not cross the blood-brain barrier. The results from the current in vitro and in vivo studies indicate that [18F](+)-FBT is a promising ligand for studying cholinergic terminal density, with PET, via the VAcChT.
... Kathleen A. Grant 1,2 ,; Carol A. Shively 2 ,; Michael A. Nader 1 ,; Richard L. Ehrenkaufer 3... more ... Kathleen A. Grant 1,2 ,; Carol A. Shively 2 ,; Michael A. Nader 1 ,; Richard L. Ehrenkaufer 3 ,; Scott W. Line 3 ,; Thomas E. Morton 3 ,; H. Donald ... Department of Physiology & Pharmacology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina ...
A series of brain uptake studies and PET imaging studies were conducted with the sigma(1) selecti... more A series of brain uptake studies and PET imaging studies were conducted with the sigma(1) selective imaging agent, [(18)F]FBFPA. The results of the study indicate that this radiotracer readily crosses the blood-brain barrier and labels sigma(1) receptors in vivo. In vivo blocking studies with a sigma(1) selective ligand and a nonselective sigma(1)/sigma(2) receptor ligand indicates that [(18)F]FBFPA labels sigma(1) and not sigma(2) receptors in rodent brain. PET imaging studies demonstrated a high uptake in regions of rhesus monkey brain having a high density of sigma(1) receptors. The uptake of [(18)F]FBFPA was displaced by the sigma ligand, haloperidol (1 mg/kg, i.v.). In vivo blocking studies indicate that the progesterone blocked the brain uptake of [(18)F]FBFPA in rat brain. These data indicate that [(18)F]FBFPA is a potential radiotracer for imaging sigma(1) receptors in the CNS in vivo with PET.
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