Synthesis and evaluation of radioiodinated terminal para-iodophenyl-substituted .alpha.- and .beta.-methyl-branched fatty acids

Abstract

Methods were developed for the preparation of terminal p-iodophenyl-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 describbed. 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 analogs demonstrated a greater myocardial retention of the methyl-branched fatty acids than the unbranched analogs. The mechanism of myocardial retention apparently results from steric or chemical inhibition of the metabolism of these fatty acids by the presence of the methyl group.