Nuclear medicine program: Progress report for quarter ending June 30, 1988

This report describes our initial studies on developing techniques of attaching radioisotopes of copper (Cu-64 and Cu-67) and rhenium (Re-186 and Re-188) to proteins. Our work has focussed on the synthesis of para-carboxyalkylphenylglyoxal-bis-(N/sub 4/-methylthiosemi-carbazone) ligands (TSC). Because of the strong binding of Cu(II) to the bis-TSC ligand, the development of bifunctional chelates for attachment of radioisotopes of copper to antibodies is of interest. We have developed an improved synthesis of the requisite ..cap alpha..-ketoaldehyde and 1,2-diketone substrates used for derivatization to the bis-TSC ligand chelates. This approach uses the ''Kornbloom'' method which provides a simple alternative to the usual method for fabrication of the 1,2-bis-thiosemicarbazone compounds and avoids the use of selenium dioxide for oxidation of substituted acetophenones. Acylation of the -phenyl carboxylic acid with bromoacetyl chloride or 2-bromopropionyl chloride followed by treatment with silver nitrate readily provides the nitrate esters. Oxidative elimination with sodium acetate in DMSO then provides the ..cap alpha..-ketoaldehyde or 1,2-diketo products. The overall yields are in the 40-60% range. Also in this report are the results of studies with the Langendorff-perfused rat heart system. Comparison of the incorporation of (I-131)IPPA and (I-125)BMIPP in dual-labeled studies under normoxia and hypoxia (pO/sub 2/ > 120 mm) clearlymore » showed the expected preferential incorporation into triglyceride (TG) storage products. Basic hydrolysis of the TG fraction purified by chromatography showed release of the radioactivity into products chromatographing in the free fatty acid fraction.« less