This project initiated the chemistry development and biologic evaluation of a new class of fatty acid analogs labeled with C-11, F-18 and I-123. The structure of these fatty acids is based on that of a betamethyl branched chain fatty acid. As such the agents developed were designed to be transported into myocardinal cells as fatty acids but to be incapable of undergoing complete metabolism. Definition of the myocardial and blood kinetics of the fatty acid analogs raised important questions concerning their relationship to metabolism. The present study will continue to refine the structure of these fatty acids in order to achieve the highest myocardial concentration and retention with fast blood clearance. Since the beta oxidation process produces stereospecifically the L-betahydroxyacyl-SCoA via the enzyme L-enoyl-CoA-hydroxylase, we propose to study the in vivo and metabolic behavior of the R nd S enantiomers of betamethyl fatty acids. Emphasis will be placed on the metabolic fate of these fatty acids. The sized and site of the different metabolic pools (monoglyceride, diglyceride, triglyceride, phospholipid, free fatty acid, and betahydroxy betamethyl heptadecanoic acid) will be determined in the heart, blood, liver and myocite subcellular compartments. In addition, the ability to employ the regional concentration of the modified fatty acid as an index of fatty acid metabolism will be determined by comparison of the regional modified fatty acid concentration with an analysis of the initial clearance slope of radiolabeled palmitate. Finally, fluorine labeled analogs of the modified fatty acids will be synthesized and tested. These studies should define the potential of these radiopharmaceuticals for evaluating and quantitating the myocardial metabolic activity for this fatty acid and lay the groundwork for subsequent quantitative metabolic studies in man.
| Livni, E; Ito, S; Kassis, A I et al. (1990) (3H/14C)beta-methylheptadecanoic acid subcellular distribution and lipid incorporation in mouse heart. Lipids 25:238-40 |
| Jones Jr, G S; Livni, E; Strauss, H W et al. (1988) Synthesis and biologic evaluation of 1-[11C]-3,3-dimethylheptadecanoic acid. J Nucl Med 29:68-72 |
| Kairento, A L; Livni, E; Mattila, S et al. (1988) Comparative evaluation of [123I]14-p-iodophenyl-beta-methyltetradecanoic acid and thallium-201 in the detection of infarcted areas in the dog heart using SPECT. Int J Rad Appl Instrum B 15:333-8 |
| Elmaleh, D R; Livni, E; Okada, R et al. (1985) The synthesis and evaluation of radioiodinated 14-(iodophenyl)-3-(R,S)methyltetradecanoic acid. Nucl Med Commun 6:287-97 |
