EFFECTS OF CONFIGURATION ON THE MYOCARDIAL UPTAKE OF RADIOIODINATED 3(R)-BMIPP AND 3(S)-BMIPP IN RATS

Radioiodinated 3(R)-(+)- and -(-)-15-(p-iodophenyl)-3-(R,S)-methylpent adecanoic acid (BMIPP) were prepared and evaluated in rats to investig ate the effects of absolute configuration of the 3(beta)-methyl group on myocardial uptake and release kinetics. Methods: The 3(R)-(+)-BMIPP analog was synthesized by initial acylation of a thiophene template w ith the acid chloride of ethyl 3(R)-methylglutarate. 3(S)-(-)-BMIPP wa s obtained by separation from the mixture of diastereomeric amides pre pared from reaction of the acid chloride of racemic BMIPP with the S-( -)-alpha-methylbenzylamine. The amide of synthetic 3(R)-BMIPP prepared from S-(-)-alpha-methylbenzylamine was identical to the chromatograph ically more polar isomer. Free acids were obtained by acid hydrolysis of the amides, fully characterized and then converted to the radioiodi nated BMIPP isomers. Results: Biodistribution studies in rats with the dual-labeled [I-131]-3(S)-BMIPP/[I-125]-3(R)-BMIPP mixture demonstrat ed greater myocardial uptake of 3(R)-BMIPP compared with the S(S)-BMIP P isomer [60 min: 3(R)-BMIPP = 4.37 %ID/g; 3(S)-BMIPP = 3.44; p < 0.05 ; 180 min, 2.31 and 1.78 %ID/G, respectively, p < 0.01], although both isomers had similar myocardial washout curves (5-180 min). Percent ID /g values for other tissues which were examined (blood, lungs, thyroid ) were similar. Conclusion: Higher myocardial uptake of the 3(R)-BMIPP isomer observed in these animal studies may suggest differences in ca rrier-mediated myocyte uptake of the two isomers. These studies sugges t that [I-123]-3(R)-BMIPP is a candidate for clinical evaluation and m ay show greater myocardial uptake than the 3(S)-BMIPP isomer and may t hus require reduced injected dose.