Methods have been developed for the preparation of terminal p-idophenyl-substituted alpha- and beta-methyl-branched long-chain fatty acids. The syntheses and physical properties of 14-(p-iodophenyl)-2(RS)-methyltetradecanoic acid and 15-p-iodophenyl)-3(RS)-methylpentadecanoic acid are described. The radioiodinated agents are of interest as a result of the expected pronounced uptake and prolonged myocardial retention that may result from the inhibition of fatty acid metabolism. Tissue distribution studies in rats with 14-(p-[125I]iodophenyl)-2(RS)-methyltetradecanoic acid and 15-(p-[125I]iodophenyl)-3(RS)-methylpentadecanoic acid show significant heart uptake and prolonged retention accompanied by low in vivo deiodination and high blood levels. A comparison of the heart uptake of the radioiodinated methyl-branched fatty acids and their unbranched analogues has demonstrated a greater myocardial retention of the methyl-branched fatty acids than the unbranched analogues. These results suggest that the mechanism of myocardial retention results from steric or chemical inhibition of the metabolism of these fatty acids by the presence of the methyl group.

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A method has been developed for the preparation of terminal halogenated tellurium fatty acids (X-R-Te-R'-COOH). The synthesis and physical properties of 17-bromo- and 17-iodo-9-telluraheptadecanoic acid (17-iodo-9-THDA) are described. The radiohalogenated agents are of interest as a result of their expected pronounced and prolonged heart uptake and potential use for evaluation of regional myocardial fatty acid metabolism. Evaluation in rats indicates that the myocardial uptake of 17-[131I]iodo-9-telluraheptadecanoic acid (17-[131I]iodo-9-THDA) is accompanied by significant in vivo deiodination. A comparison of the heart uptake and deiodination of 17-[131I]iodo-9-THDA and 16-[131I]iodopalmitic acid has demonstrated a close similarity in blood levels of radioactivity and thyroid uptake of radioiodide after administration of these agents to rats. These data suggest that the mechanism of deiodination of terminal radioiodinated alkanoic acids primarily results from direct cleavage of the carbon-iodine bond and not from loss of radioiodine from the final catabolite.

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