BMIPP-design and development

Abstract

In the early 1980s a major obstacle for myocardial SPECT using iodine-123-labeled fatty acids and imaging technology available at that time was the rapid metabolism and myocardial washout of activity. Development of the 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) fatty acid analogue was based on the established effects of methyl-branching in delineating the enzymatic aberration in Refum's disease and our early studies with the tellurium (Te)-substituted fatty acid analogues. Extensive animal studies with the Te-fatty acids demonstrated that this major structural alteration did not affect initial myocardial extraction, but could successfully inhibit subsequent metabolism and significantly delay washout. Tracer kinetic evaluation and metabolic studies on experimental animals and Langendorff-perfused rat hearts clearly demonstrated that introduction of methyl-branching is an effective approach which alters tracer kinetics by delaying myocardial washout of radioiodinated fatty acids by increasing myocardial retention. Although irreversible retention of iodine-123 BMIPP is not observed, subsequent extensive human studies have clearly substantiated the delayed myocardial washout of BMIPP in comparison with the p-IPPA straight chain analogue. Although contemporary SPECT capabilities allow much more rapid acquisition periods, the delayed washout is still a practical benefit in relation to the use of BMIPP. Most important, the unexpected mis-match which has been widely observed between perfusion tracer distribution and the regional BMIPP distribution (i.e. BMIPP < flow tracer) has been linked to the identification of jeopardized, but viable myocardial regions. In this paper the development of BMIPP is discussed and the results of recent studies focusing on evaluating the effects of the absolute configuration of the branched methyl group using the 3(R)-BMIPP and 3(S)-BMIPP are described.