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（逐字摘自申请人摘要）： 异常情况 长链脂肪酸的β-氧化先于功能异常和 心脏缺血性和非缺血性疾病中不可逆的组织损伤。 拟议的工作研究了棕榈酸的代谢和动力学 类似物，16-[F-18]氟-4-硫杂-十六烷酸（FTP）和油酸酯类似物， 1 8-[F- 1 8]氟-4-硫杂-9Z-十八碳烯酸 (FTO)，位于离体大鼠心脏中。 调查将尝试 1) 评估 FTP 和 FTO 的敏感性 β-氧化并选择两种示踪剂之一以进一步详细了解 代谢和验证研究，2) 表征捕获的 F-18 标记 FTP/FTO 在心肌中的代谢物以澄清捕获 机制，3）确定示踪剂代谢捕获率的关系 在心脏中，外源脂肪酸的氧化率范围广泛 状况。分离的缓冲液灌注大鼠心脏制剂与外部 这些研究中使用了放射性检测。新陈代谢 FTP/FTO 在心肌中转化为 F-18 标记的酰基辅酶A、烯酰基辅酶A、酰基肉碱、 甘油三酯和心脏中的复合脂质将通过薄层来估计 色谱法和高效液相色谱法。凝胶电泳 将用于分析与细胞蛋白质结合的放射性 代谢加工的结果。示踪关系实验 不同条件下对棕榈酸酯和油酸酯氧化的捕获率 为定量技术的开发提供关键数据 使用 PET 对心肌脂肪酸氧化率进行区域评估。