Nuclear Medicine Program progress report for quarter ending September 30, 1988

During this period the properties of the unknown metabolite released from Langendorff-perfused rat hearts administered radioiodinated 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) have been further evaluated. Identification of this metabolite is important to provide a better understanding of the myocardial metabolism of methyl-branched fatty acids and to illuminate the factors affecting myocardial retention of such agents. The metabolite is the principal component in the outflow of the isolated rat hearts. Following isolation and purification of the metabolite, treatment with NaBH/sub 4/ had no effect on the chromatographic properties. In contrast, a much less polar product was formed by treatment with acetic anhydride, suggesting the presence of a primary or secondary hydroxyl group. In addition, the metabolite is soluble in dilute base and extracted from an acid solution with ether, demonstrating the presence of a carboxyl group. These combined results suggest BMIPP is metabolized to a hydroxy acid of unknown structure. Studies are now in progress to identify this material. Studies of the effects of chain length on the complexation of a series of p-carboxyalkylphenylglyoxal bis-(N-alkylthiosemicarbazones) (TSC) have continued. After complexation with either Cu-64 or Cu-67 followed by activation to the tetrafluorophenyl esters, the bifunctional ligands were attached to BSA and purified by G-25more » Sephadex. Yields varied from 2--3% to 40%, with higher yields for the shorter chain analogues. Because of simpler formation and higher yield, future studies will focus on the radiolabeling of antibodies with the short-chain analogues of the 1,2-diketone TSC derivatives. Also during this period (I-131)IPPA was supplied to collaborators at the Institute of Clinical and Experimental Nuclear Medicine in Bonn, West Germany, for studies with an isolated working rat heart model.« less