PET TRACERS FOR MYOCARDIAL FATTY ACID OXIDATION

用于心肌脂肪酸氧化的 PET 示踪剂

• 批准号: 6627536
• 负责人: Timothy R. DeGrado
• 金额: $ 20.92万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6627536
• 关键词: bioimaging /biomedical imaging; biomaterial development /preparation; biotechnology; cardiac myocytes; cardiovascular disorder diagnosis; chemical kinetics; chemical synthesis; diagnosis design /evaluation; fatty acid analog; fatty acid binding protein; fatty acid metabolism; heart disorder; heart metabolism; high performance liquid chromatography; intermolecular interaction; laboratory rat; myocardium; oleate; oxidation; palmitates; pharmacokinetics; positron emission tomography; radiotracer; thin layer chromatography

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.

描述（摘自申请人摘要）：异常