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Design, synthesis and evaluation of redox radiopharmaceuticals: a potential new approach for the development of brain imaging agents

Conference ·
OSTI ID:5887031
The fabrication and complete evaluation are described of a dihydropyridine in equilibrium pyridinium salt type redox system for the delivery of radioiodinated agents to the brain. The pivotal intermediate, N-succinimidyl (1-methylpyridinium iodide)-3-carboxylate was prepared by condensation of nicotinic acid and N-hydroxysuccinimide in the presence of dicyclohexylcarbodimide, followed by quaternization of III with methyl iodide. Tissue distribution studies of /sup 125/I-labeled 4-iodoaniline and the redox agents were performed in rats. (/sup 125/I)Iodoaniline initially showed moderate (0.58% dose/gm) brain uptake with subsequent release of the radioactivity from the brain. (/sup 125/I)Iodoaniline, when coupled to a dihydropyridine carrier showed higher uptake and retention in the brain. The (/sup 125/I)iodophenylethyl analogue showed uptake and retention in the brain to be very similar. Apparently the lipophilic agents cross the blood-brain barrier and are oxidized (quaternized) within the brain. The blood-brain barrier then prevents their release resulting in high uptake and retention in the brain and high brain:blood ratios. 11 refs., 3 figs.
Research Organization:
Oak Ridge National Lab., TN (USA)
DOE Contract Number:
AC05-84OR21400
OSTI ID:
5887031
Report Number(s):
CONF-8606111-2; ON: DE86009462
Country of Publication:
United States
Language:
English