A modified radiolabled fatty acid, 3-methyl-[1-11C]-heptadecanoate (MFA), was developed in our laboratory for the evaluation of regional myocardial metabolism. The radiopharmaceutical localized in the hearts of experimental animals and man with a residence half time approximately 100 times longer than palmitate. Preliminary isolated organ perfusion experiments suggested that metabolism was via omega oxidation. The proposed research will characterize both the biochemical pathways employed in the metabolism of this substance and the kinetic behavior of the material in a manner suitable for application to a metabolic model. This model will define the parameters that must be known to relate the regional distribution of MFA in the myocardium to the regional metabolism of fatty acids under a wide variety of circumstances. Specific studies will be performed comparing MFA to palmitate in isolated perfused organs and in dogs to characterize the biochemical pathways and determine the effect of hypoxia, acidosis, and availability of alternative substrates on myocardial fatty acid behavior. Studies will also be performed in human volunteers to establish the changes in MFA myocardial behavior from rest to exercise, and following ingestion of a meal. Finally, a second MFA, 3,15-dimethyl-[1-11C]-hepatadecanoate, will be synthesized and tested in isolated perfused organs. This substance should not be metabolized by either beta or omega oxidation, and my provide an additional imaging probe to study myocardial fatty acid metabolism.
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