Project: Research project

Project Details


DESCRIPTION (Verbatim from the Applicant's Abstract): 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.
Effective start/end date1/1/0112/31/04


  • Medicine(all)