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

Nuclear Medicine Group, Oak Ridge National Laboratory, Oak Ridge, Tennessee
Department of Nuclear Medicine, University of Essen, Essen
Department of Nuclear Medicine, University Hospital, Carl Gustav Technical University, Dresden, Germany

Correspondence: For correspondence or reprints contact: F.F. (Russ) Knapp, Jr., PhD, Nuclear Medicine Group, Bldg. 4501, Oak Ridge National Laboratory, P.O. Box 2008, Oak Ridge, TN 37831-6229.

ABSTRACT

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 [¹²⁵I]-3(R)/[¹³¹I]-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 ¹²⁵I and ¹³¹I 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 ¹²⁵I and ¹³¹I in the lipid, aqueous and pellet samples were similar for both isomers. Distribution of ¹²⁵I and ¹³¹I 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 (C₁₈) of the FFA fraction showed similar ¹²⁵I and ¹³¹I profiles, corresponding to BMIPP, and the -methyl-Cu₁₄ (14-(p-iodophenyl)-3-(R,S)-methyltetradecanoic acid) and C₁₂, C₁₀ and C₆ carbon chainlength catabolites. By TLC, radioactive components of ¹²⁵I and ¹³¹I in the urine had the same TLC mobility as hippuric acid. HPLC analyses (C₁₈) of acid-hydrolyzed urine gave a single ¹²⁵I/¹³¹I component with the same relative retention time as 2-(p-odophenyl)acetic acid, which is the final /ß-oxidative BMIPP catabolite. Unexpectedly, HPLC of lipids from base-hydrolyzed TG from the heart tissue showed ¹²⁵I|/131I 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.

Key Words: radioiodinated fatty acids • 3(R)/3(S)-15-(p-iodophenyl)-3-methylpentadecanoic acid • cardiac imaging agents

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