PET TRACERS FOR MYOCARDIAL FATTY ACID OXIDATION

Project: Research project

Description

DESCRIPTION Abnormalities of beta-oxidation of long-chain fatty acids preceeds functional abnormalities and irreversible tissue injury in ischemic and nonischemic diseases of the heart. The proposed work investigates the metabolism and kinetics of the palrnitate analog, 16-[F-18]fluoro-4-thia-hexadecanoic acid (FTP), and the oleate analog, 1 8-[F- 1 8]fluoro-4-thia-9Z-octadecenoic acid (FTO), in isolated rat heart. The investigations will attempt to 1) evaluate the sensitivities of FTP and FTO to beta-oxidation and select one of the two tracers for further detailed metabolic and validation studies, 2) characterize the trapped F-18 labeled metabolites of FTP/FTO in the myocardium in order to clarify the trapping mechanism, and 3) determine the relationship of tracer metabolic trapping rate in the heart with oxidation rates of exogenous fatty acids in a broad range of conditions. Isolated buffer-perfused rat heart preparations with external radioactivity detection are utilized in these studies. The metabolism of FTP/FTO in the myocardium to F-18 labeled acyl-CoA, enoyl-CoA, acyl-carnitine, triglycerides, and complex lipids in heart will be estimated by thin-layer chromatography and high-performance liquid chromatography. Gel-electrophoresis will be utilized to analyze radioactivity bound to cellular proteins as a consequence of metabolic processing. Experiments on the relationship of tracer trapping rate to palmitate and oleate oxidation under various conditions will provide critical data toward the development of a technique for quantitative regional assessment of fatty acid oxidation rate in myocardium using PET.
StatusFinished
Effective start/end date1/1/0112/31/04

Funding

  • National Institutes of Health: $260,750.00
  • National Institutes of Health: $312,379.00
  • National Institutes of Health: $209,178.00
  • National Institutes of Health: $60,322.00

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Fatty Acids
Oxidation
Acyl Coenzyme A
Radioactivity
Oleic Acid
Metabolism
Rats
Thin layer chromatography
Enzyme kinetics
Palmitic Acid
Carnitine
Palmitates
High performance liquid chromatography
Metabolites
Electrophoresis
Buffers
Triglycerides
Gels
Tissue
Lipids

ASJC

  • Medicine(all)