Nuclear medicine progress report for quarter ending March 31, 1984

In this report the evaluation of a new potential approach for brain-specific delivery of radioiodinated agents is described. These studies were supported by ORNL Seed Money funds. The p-aminophenethylamine group was attached as an amide linkage to the methyliodide quaternized form of nicotinic acid by reaction with the activated succinimidyl ester. The p-amino group was converted to the piperidinyl triazene and iodine-125 introduced into the p-position by decomposition with H/sup 125/I. Following reduction of the pyridinium ring with NaBH/sub 4/, the dihydro form was administered to rats and showed good brain uptake (5 min, approx. 0.3% dose). The quaternary compound, however, showed low brain uptake (5 min, approx. 0.03% dose). These studies suggest that the dihydro agent readily crosses the intact blood:brain barrier and is quaternized in vivo preventing its release. In contrast, the administered quaternary form cannot cross the blood:brain barrier and thus shows low brain uptake. These data demonstrate that brain-specific delivery of radiopharmaceuticals using this method is possible and several other model compounds are being evaluated. Studies of new radiolabeled fatty acids for the evaluation of heart disease were extended to investigate the subcellular distribution of various agents in rat heart cells following intravenous administration. Distribution profilesmore » were determined for six radiolabeled structurally-modified fatty acids, including two Te fatty acids and three 3-methyl-branched fatty acids. It was determined that those agents which show low myocardial uptake also show low localization in microsomal and mitochrondrial fractions. Subcellular distribution experiments coupled with lipid analysis of the fractions to determine the relation between uptake, metabolism and incorporation within the various lipid pools are continuing. 5 references, 1 figure, 4 tables.« less