Nuclear medicine program progress report for quarter ending December 31, 1993

The results of preliminary in vivo metabolic studies of the iodine-125-labeled E-(R,R)-IQNP in rats are described. The E-(R,R) isomer demonstrates highly selective and specific localization in cerebral regions rich in the m{sub 1} and m{sub 4} muscarinic-cholinergic receptor subtypes and is a good candidate for potential human studies. Since the external evaluation of receptor-ligand complexes requires that only uptake of the unmetabolized agent is measured, these studies were performed to evaluate the metabolism of the radioiodinated ligand in the whole brain, heart, liver and serum from rats at several time points after intravenous administration. Radioactivity was very rapidly excreted in the first 24-hour period (urine = 46; feces = 26). Folch extracts of the different tissue samples showed that the lipid-soluble extract from brain tissue contained 87 of the activity at 24 hours. In the heart, 62 of the activity was extracted in the lipid soluble extract after 30 minutes and decreased to 51 after 4 hours. Thin-layer chromatographic analysis of the lipid soluble extracts indicated that only the unmetabolized E-(R,R)-IQNP was detected in brain extracts. Also in this report, the predicted medical radioisotope production capabilities of the proposed Advanced Neutron Source (ANS) are discussed.