Nuclear medicine progress report for quarter ending September 30, 1987

In this report the preparation of a new radioiodinated nucleoside as a potential tumor-localizing agent is described. The p-iodophenyl analogue of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide (AlCA) was prepared by a 5-step reaction sequence. The iodine-125-labeled analogue was evaluated in rats and nude mice with implanted tumors. This agent crossed the intact blood-brain barrier (0.28% injected dose/gm at 5 min) and also showed some uptake in implanted tumors (0.74% injected dose/gm at 30 min). These preliminary results demonstrate that radioiodinated nucleoside analogues are good candiates for tumor localization. To evaluate the possible formation of 3-R,S-hydroxy-3-methyl metabolites from radioiodinated 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (''BMIPP''), a new synthesis of 3-R,S-hydroxy fatty acids has been developed involving C-2 acylation of the ester (''Meldrum's'' acid) formed by condensation of malonic acid with acetone. Treatment with acid forms the methyl ketone which is condensed under Reformatsky conditions to give the racemic β-hydroxy-β-methyl ester which is then hydrolyzed with base. In this way, the β-hydroxy analogues of BMIPP and 3-methylheptadecanoic acid have been prepared for the first time and are being used in biological studies. 8 refs., 3 figs., 2 tabs