Synthesis and evaluation of radioiodinated ligands for the study of peripheral benzodiazepine receptors using SPECT
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Date
2002-04-29
Journal Title
Journal ISSN
Volume Title
Publisher
Australian Nuclear Science and Technology Organisation
Abstract
The peripheral benzodiazepine receptor (PBR) is a multimeric protein complex located in the outer mitochondrial membrane and predominantly found in steroid producing organs and glial cells in the brain. The PBR have been implicated in the control of cell proliferation and differentiation and shown to display increased levels in a variety of malignant tumours and neurodegenerative disorders. A series of potent imidazo[1,2-a]pyridines have been prepared for development as radiopharmaceuticals to study these disorders in patients using nuclear medicine imaging techniques. In vitro studies indicate that compounds substituted with an electronegative atom in the 6 position of the pyridine ring, a lipophilic group or halogen in the 4'-position of the 2-phenyl ring, and lower alkyl methyl or ethyl substituents on the amide nitrogens of the side chain, exhibit high affinity and selective binding. ' N'N'-dimethyl- and the N'N'-diethyl 6-chloro-(4'-iodophenyl)imidazo[1,2-a]pyridine-3-acetamide 1 and 2 displayed optimum in vitro properties and were thus selected for radiolabelling with the diagnostic radionuclide iodine-123. Radioiodination was achieved by iododestannylation of the corresponding tributyl stannane precursor in the presence of peracetic acid. Purification by C-18 reverse phase HPLC gave the desired products in 70-80% radiochemical yields and in greater than 98% radiochemical purity. Biodistribution studies in normal rodents indicated high uptake of radioactivity in tissues with known PBR sites. Preliminary imaging studies in rodents bearing mammary adenocarcinomas indicated high uptake in the tumour with retention of activity after 24 h. The synthesis, structure activity studies, radiolabelling and biological studies of these compounds will be presented.
Description
Keywords
Biological accumulation, Imidazoles, Iodine 123, Nervous system diseases, Organic iodine compounds, Pyridines, Radiochemical analysis, Radiopharmaceuticals, Receptors, Single photon emission computed tomography, Synthesis
Citation
Katsifis, A., Mattner, F., Mardon, K., Dikic, B., Papazian, V., & Greguric, I. (2002). Synthesis and evaluation of radioiodinated ligands for the study of peripheral benzodiazepine receptors using SPECT. Poster presented to the France-Australia Symposium on nuclear medicine : methodology, clinical applications and pharmacology : volume of proceedings, Sheraton on the Park, Sydney, Australia, Monday 29th April 2002. Lucas Heights, NSW : Australian Nuclear Science and Technology Organisation, (pp. 63).