MYOCARDIAL EXTRACTION OF 1-[C-11]BETAMETHYLHEPTADECANOIC ACID

Betamethylheptadecanoic acid (BMHA) is a branched chain fatty acid analog that is transported into myocardial cells by the same long chain fatty acid carrier protein mechanism as natural fatty acids, but cannot be completely catabolized and accumulates in the tissue. Thus, C-11-labeled BMHA is a useful tracer for the noninvasive evaluation of myocardial fatty acid utilization by positron emission tomography (PET). Methods: As a prelude to PET studies, the metabolism of BMHA was studied by classical techniques. We measured the net extraction fraction (E(n)) of 1-[C-11]-beta-R,S-methylheptadecanoic acid (1-[C-11]BMHA) and compared it to that of natural fatty acids in dogs, using arterial/venous measurements and a mathematical model. Two groups of conditioned dogs were studied. In the first group, measurements were made under fasting (normal control) conditions and in the second group, measurements were made during glucose and insulin infusion. Myocardial blood flow, and the extraction/utilization of other substrates (glucose, oxygen and lactate) were also measured. Results: For natural fatty acids in the basal state, E(n)(FA) was 0.335. After glucose/insulin infusion, this value decreased to 0.195. The 1-[C-11]BMHA showed a similar decrease in E(n)(BMHA) from 0.220 in the control group to 0.100 in the group treated with glucose/insulin infusion. Preliminary PET studies with 1-[C-11]BMHA verified the validity of performing these measurements noninvasively. Conclusion: The results of these studies indicate that rates of fatty acid metabolism in the myocardium can be determined from steady-state concentrations of 1-[C-11]BMHA.