PET TRACERS FOR MYOCARDIAL FATTY ACID OXIDATION

用于心肌脂肪酸氧化的 PET 示踪剂

• 批准号: 6260460
• 负责人: Timothy R. DeGrado
• 金额: $ 31.24万
• 依托单位: DUKE UNIVERSITY
• 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/6260460
• 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（来自申请人摘要的逐字记录）： 长链脂肪酸的β-氧化导致功能异常， 心脏缺血性和非缺血性疾病中的不可逆组织损伤。 拟议的工作调查的代谢和动力学的棕榈酸酯 类似物，16-[F-18]氟-4-硫代-十六烷酸（FTP），和油酸酯类似物， 18-[F-18]氟-4-硫杂-9Z-十八碳烯酸（FTO）。 调查将试图1）评估FTP和FTO的敏感性 选择两种示踪剂中的一种， 代谢和验证研究，2）表征捕获的F-18标记 心肌中FTP/FTO的代谢产物，以澄清捕获 3）确定了示踪剂代谢捕获率的关系 在心脏中，外源性脂肪酸的氧化率在很宽的范围内， 条件用外部缓冲液灌注的大鼠心脏制备物 在这些研究中使用放射性检测。的代谢 F-18标记的酰基-CoA、烯酰基-CoA、酰基-肉毒碱， 心脏中的甘油三酯和复合脂质将通过薄层色谱法进行估计。 色谱法和高效液相色谱法。凝胶电泳 将被用来分析结合到细胞蛋白质的放射性， 代谢过程的结果。示踪剂关系实验 在各种条件下对棕榈酸酯和油酸酯氧化的捕获率将 为定量技术的发展提供关键数据， 使用PET对心肌脂肪酸氧化率进行区域评估。