We have developed methods for the preparation of a new class of fatty acid analogs labeled with C11, P18 and I123. The structure of these fatty acids is based on that of betamethyl branched chain fatty acids. As such, the agents developed were designed to be transported into myocardial cells as fatty acids but to be incapable of undergoing complete metabolism. A series of betamethyl branched chain fatty acid was synthesized, labeled and evaluated in preliminary studies in rats. In the present study we will concentrate on completing the evaluation of the tracer of choice, 1-(C- 11)betamethylheptadecanoic acid, (1-(C-11)BMHA), by determining its biochemical behavior and its myocardial kinetics in order to establish its usefulness as a tracer for studying myocardial metabolism. These studies, will permit the development of an operational mathematical model for quantitative determination of fatty acid metabolism in the canine heart. In addition, this modified fatty acid as an index of fatty acid metabolism will be compared to that of the """"""""physiological"""""""" tracer, 1(C-11)palmitic acid (1(C11)PA). The comparison will be done for different metabolic states and varying substrate availability. The position imaging studies and the operational equation will be validated against the AV differences study. The site and size of the metabolic pools 1(C11)BMHA will be determined using several approaches. These studies should complete the definition of the potential of this fatty acid for evaluating and quantitating the myocardial metabolic activity in an animal model and lay the groundwork for subsequent quantitative metabolic studies in man.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL029462-06
Application #
3340575
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1982-08-01
Project End
1989-09-29
Budget Start
1987-09-30
Budget End
1988-09-29
Support Year
6
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
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