Dual-Label Studies with [125I]-3(R)/[131I]-3(S)-BMIPP Show Similar Metabolism in Rat Tissues

Biodistribution studies with the radioiodinated 3(R)- and 3(S)-isomers of 15-(p-iodophenyl)-3-methylpentadecanoic acid (BMIPP) in rats have shown that 3(R)-BMIPP has 20%-25% higher heart uptake than 3(S)-BMIPP (15-180 min). In contrast, the 3(S)-isomer has slightly higher liver uptake, and uptake in other tissues examined is similar. Methods: To evaluate the possible differences in metabolic fate of the two isomers, a mixture of [ 125 I]-3(R)/[ 131 I]-3(S)-BMIPP was administered to fasted female Fisher rats. Groups of rats (3 per group) were killed 15, 60 and 180 min after administration. Urine and feces were collected from a fourth group (n = 3) over 7 d. Samples of blood, heart, liver, lungs, kidney and urine were Folch extracted. The distributions of 125 I and 131 I in the organic (lipid), aqueous and pellet samples were determined. The lipid samples as well as the organic fractions from base-hydrolyzed triglyceride (TG) fractions and acid-hydrolyzed urine samples were then analyzed by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). Results: The relative distributions of 125 I and 131 I in the lipid, aqueous and pellet samples were similar for both isomers. Distribution of 125 I and 131 I in the various components of the lipid extracts observed by TLC (hexane:ether: HOAc, 70:30:1) was also similar, with principal incorporation into the free fatty acid (FFA) and TG pools. HPLC analyses (C 18 ) of the FFA fraction showed similar 125 I and 131 I profiles, corresponding to BMIPP, and the α-methyl-C 14 (14-(p-iodophenyl)-3-(R,S)-methyltetradecanoic acid) and C 12 , C 10 and C 6 carbon chain-length catabolites. By TLC, radioactive components of 125 I and 131 I in the urine had the same TLC mobility as hippuric acid. HPLC analyses (C 18 ) of acid-hydrolyzed urine gave a single 125 I/ 131 I component with the same relative retention time as 2-(p-iodophenyl)acetic acid, which is the final α/β-oxidative BMIPP catabolite. Unexpectedly, HPLC of lipids from base-hydrolyzed TG from the heart tissue showed 125 I/ 131 I components with the same retention times as shorter-chain fatty acids, similar to the FFA fraction, with only low levels of activity detected in BMIPP. Conclusion: These results show that 3(R)-BMIPP and 3(S)-BMIPP are metabolized similarly in rat tissues and that higher myocardial extraction observed for 3(R)-BMIPP may reflect differences in the relative membrane transport of the two isomers.