Novum

Background: The biotin-avidin interaction remains a gold standard for the two-step pretargeting approach to image tumor sites. We aim to develop two-step pretargeting systems utilizing 99m Tc labeled biotin functionalized macrocyclic chelating agents synthesized using the highly e cient Cu(I) catalyzed azide-alkyne cycloaddition for potential radioimaging applications. Methods: A facile synthesis of DOTA-Triazole-Biotin, radiocomplexation with 99m Tc and the pretargeting protocol is described. The synthesis features Cu(I) catalyzed click conjugation between biotinylated azide and propynyl functionalized DO3A. 99m Tc radiolabeling was performed to detect the accumulation of avidin as the pretargeting agent. Cytotoxicity was determined using the trypan blue exclusion assay, macrocolony, and MTT assay. Cell uptake studies were performed using radiolabeled DOTA-Triazole-Biotin and compared with avidin treated cells for 2 h. Tumor imaging was performed in U-87MG cell line implanted tumor bearing nude mice and uptake of the radiotracer was estimated. Results: All compounds have been successfully characterized by NMR and MS spectroscopy. More than 96% radiolabeling e ciency was obtained and the radioconjugate exhibited su cient stability under physiological conditions. Conclusion: To summarize, a new candidate for avidin based two-step pretargeting of tumors has been synthesized and evaluated for potential imaging and diagnostic applications. The chelate possesses high stability under physiological conditions, exhibits e ective interaction with its avidin target, and low nonspeci c retention in vivo.

Regioisomeric spiro-(indoline-isoxazolidines) have been synthesized in moderate yields by the cycloaddition reaction between ethyl (3-indolylidene)acetate and various substituted a,N-diphenylnitrones, using environmentally benign microwave technology. A novel concerted reaction mechanism is described that explains the preferential formation of the regioisomeric spiro-(indoline-isoxazolidine) analogs 6 over 5. These compounds were screened for anti-mycobacterial and anti-invasive activities against tumor cells.

The amyloid-␤ peptide (A␤) can generate cytotoxic oligomers, and their accumulation is thought to underlie the neuropathologic changes found in Alzheimer's disease. Known inhibitors of A␤ polymerization bind to undefined structures and can work as nonspecific aggregators, and inhibitors that target conformations that also occur in larger A␤ assemblies may even increase oligomerderived toxicity. Here we report on an alternative approach whereby ligands are designed to bind and stabilize the 13-26 region of A␤ in an ␣-helical conformation, inspired by the postulated A␤ native structure. This is achieved with 2 different classes of compounds that also reduce A␤ toxicity to cells in culture and to hippocampal slice preparations, and that do not show any nonspecific aggregatory properties. In addition, when these inhibitors are administered to Drosophila melanogaster expressing human A␤ 1-42 in the central nervous system, a prolonged lifespan, increased locomotor activity, and reduced neurodegeneration is observed. We conclude that stabilization of the central A␤ ␣-helix counteracts polymerization into toxic assemblies and provides a strategy for development of specific inhibitors of A␤ polymerization.

Receptors for some regulatory peptides are highly expressed in tumors. Selective radiolabeled peptides can bind with high affinity and specificity to these receptors and exhibit favorable pharmacologic and pharmacokinetic properties, making them suitable agents for imaging or targeted therapy. The success encountered with radiolabeled somatostatin analogs is probably the first of a long list, as multiple peptide receptors are now recognized as potential targets. This review focuses on 3 neuropeptide receptor systems (bombesin, neurotensin, and neuropeptide-Y) that offer high potential in the field of nuclear oncology. The underlying biology of these peptide/receptor systems, their physiologic and pathologic roles, and their differential distribution in normal and tumoral tissues are described with emphasis on breast, prostate, and lung cancers. Radiolabeled analogs that selectively target these receptors are highlighted.

With the availability of multiple positron emission tomography (PET) tracers for neurooncology, there is a need to define the appropriate tracer in a given clinical setting, and it is in this regard that we undertook this study to directly compare F-18 flurodeoxyglucose (FDG) PET and C-11 methionine (MET) PET for the evaluation of recurrence in primary brain tumors. Patients and Methods: Thirty-seven patients with a history of treated primary brain tumors referred for evaluation of recurrent disease were initially included in the study. Two patients had to be excluded because of insufficient follow-up. There were 23 males and 12 females, mean age: 33.7 Ϯ 16.4 years; range: 5 to 65 years. All patients underwent the MET and FDG study on the same day. Visual image interpretation was performed independently by 2 PET physicians for each tracer using the plain PET and fused PET/CT images; the FDG images were evaluated first. Images were analyzed semiquantitatively using tumor to normal contralateral cortex ratios (T/N). Each patient was followed up for a minimum of 18 months. Imaging results were compared with histopathology on tumor excision or biopsy in 14 patients and with clinical follow-up and MRI/MRS at the end of 18 months in 21 patients. Results: The final diagnosis was tumor recurrence in 24 patients and no recurrence/stable disease in 11 patients. On FDG, findings in 15/35 (42%) were suggestive of recurrent tumors. On MET, findings in 24/34 (70.5%) cases were suggestive of recurrent tumors. Spatially separated secondary lesions including intraventricular deposits were clearly delineated in 5 cases, 3 were glioblastoma multiforme (GBM) and 2 were anaplastic astrocytomas. One of the secondary lesions was missed on FDG PET. Using a cutoff for T/N ratio on FDG of Ͼ0.75 to differentiate recurrence from no recurrence, sensitivity of FDG was 81.2% (confidence interval ͓CI͔ ϭ 54.4%-96%), whereas specificity was 88.9% (CI ϭ 51.8%-99.7%). Area under the curve was 0.819 (CI ϭ 0.615-0.943), P ϭ 0.0003. Using a cutoff for T/N ratio of Ͼ1.9 to differentiate recurrence from no recurrence, sensitivity of MET was 94.7% (CI ϭ 74.0%-99.9%), whereas specificity was 88.89% (CI ϭ 51.8%-99.7%). Area under the curve was 0.942 (CI ϭ 0.785-0.995), P Ͻ 0.0001. Interobserver agreement, coefficient, for MET was 0.93, suggesting good interobserver agreement, whereas for FDG, it was fair (0.23). Conclusions: MET should be the radiotracer of choice in the evaluation of recurrence of primary brain tumors because the sensitivity for detection and delineation of the possible recurrent tumor, as well as secondary deposits, is higher with MET. MET-PET is an easier technique to interpret, irrespective of the glioma grade, with less interobserver variability and straightforward localization of tumorous accumulation.

Two novel 3 0 -substituted carboxycylopropylglycines, (2S,1 0 S,2 0 S,3 0 R)-2-(3 0 -xanthenylmethyl-2 0 -carboxycyclopropyl)glycine (8a) and (2S,1 0 S,2 0 S,3 0 R)-2-(3 0 -xanthenylethyl-2 0 -carboxycyclopropyl)glycine (8b), were synthesized and evaluated as mGluR ligands. Compound 8b showed to be a potent group II antagonist with submicromolar activity. #

, has an unshielded bunker type medical cyclotron (16.5 MeV) for the production of positron emitting radionuclides namely 18 F, 15 O, 13 N and 11 C. The pharmaceuticals labeled with these radioisotopes are used for positron emission tomography (PET) imaging. The medical cyclotron facility has an associated radiochemistry facility that contains chemistry modules housed in adequately shielded hot cells meant for the synthesis of the pharmaceuticals labeled with these positron emitters. The facility also has a beam extension room. The radiation levels were measured in the facility at different locations namely cyclotron vault, control console, radiochemistry laboratory, beam extension room and the stack using a comprehensive computerized monitoring system. The radiation levels were observed to be well within the prescribed limits.

Background: The biotin-avidin interaction remains a gold standard for the two-step pretargeting approach to image tumor sites. We aim to develop two-step pretargeting systems utilizing 99m Tc labeled biotin functionalized macrocyclic chelating agents synthesized using the highly e cient Cu(I) catalyzed azide-alkyne cycloaddition for potential radioimaging applications. Methods: A facile synthesis of DOTA-Triazole-Biotin, radiocomplexation with 99m Tc and the pretargeting protocol is described. The synthesis features Cu(I) catalyzed click conjugation between biotinylated azide and propynyl functionalized DO3A. 99m Tc radiolabeling was performed to detect the accumulation of avidin as the pretargeting agent. Cytotoxicity was determined using the trypan blue exclusion assay, macrocolony, and MTT assay. Cell uptake studies were performed using radiolabeled DOTA-Triazole-Biotin and compared with avidin treated cells for 2 h. Tumor imaging was performed in U-87MG cell line implanted tumor bearing nude mice and uptake of the radiotracer was estimated. Results: All compounds have been successfully characterized by NMR and MS spectroscopy. More than 96% radiolabeling e ciency was obtained and the radioconjugate exhibited su cient stability under physiological conditions. Conclusion: To summarize, a new candidate for avidin based two-step pretargeting of tumors has been synthesized and evaluated for potential imaging and diagnostic applications. The chelate possesses high stability under physiological conditions, exhibits e ective interaction with its avidin target, and low nonspeci c retention in vivo.

A silent epidemic of modern world and largely neglected field in drug development is traumatic brain injury. There is no treatment available for the patients suffering from brain trauma. Peptide is a naturally occurring biological alternative that could represent a new generation of future medications. Authors have designed and modified the C-terminal amino acids of KDI peptide responsible for neurite growth. The inclusion of a Cys (C), Gly (G), Cys and Pro (P) amino acids in the sequence leads to the possibility of better binding with the target receptor 3T1M as compared to the known KDI sequence for neurite growth. Studies on human SH-SY5Y cells for neurite outgrowth demonstrates that the CGCKDP could plausibly be useful in neuroregeneration in neurodegenerative disorders by neurite growth formation.

In December 2019, the emergence and expansion of novel and infectious respiratory virus SARS-CoV-2 originated from Wuhan, China caused an unprecedented threat to the public health and became a global pandemic. SARS-CoV-2 is an enveloped, positive sense and single stranded RNA virus belonging to genera betacoronavirus, of Coronaviridae family. The viral genome sequencing studies revealed 75-80% similarity with SARS-CoV. SARS-CoV-2 mainly affects the lower respiratory system and may progress to pneumonia and Acute Respiratory Distress Syndrome (ARDS). Apart from lifethreatening situations and burden on the global healthcare system, the COVID-19 pandemic has imposed several challenges on the worldwide economics and livelihood. The novel pathogen is highly virulent, rapidly mutating and has a tendency to cross the species boundaries such as from bats to humans through the evolution and natural selection from intermediate host. In this review we tried to summarize the overall picture of SARS-CoV-2 including origin/ emergence, epidemiology, pathogenesis, genome organization, comparative analysis with other CoVs, infection and replication mechanism along with cellular tropism and immunopathogenesis which will provide a brief panoramic view about the virus and disease.