PET TRACERS FOR MYOCARDIAL FATTY ACID OXIDATION

描述(逐字摘自申请者摘要)：异常 长链脂肪酸的β-氧化先于功能异常和 心脏的缺血性和非缺血性疾病中不可逆的组织损伤。 拟议的工作研究帕罗硝酸酯的新陈代谢和动力学。 类似物，16-[F-18]氟-4-硫代十六烷酸(FTP)和油酸盐类似物， 18-[F-18]氟-4-硫代-9Z-十八碳烯酸(FTO)。 这些调查将试图1)评估ftp和fto的敏感性 以进行β氧化，并从两种示踪剂中选择一种以进行更详细的 代谢和验证研究，2)表征捕获的F-18标记 心肌中FTO/FTO代谢物的研究 机理，以及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在很大范围内 条件。体外缓冲灌流大鼠心脏制剂 在这些研究中使用了放射性检测。的新陈代谢 F-18标记的酰辅酶A、烯醇辅酶A、酰肉碱在心肌中的FTO/FTO 甘油三酯，以及心脏中的复杂脂质将通过薄层来估计 层析和高效液相色谱。凝胶电泳法 将被用来分析结合到细胞蛋白质上的放射性 代谢过程的结果。示踪剂关系的实验研究 不同条件下对棕榈酸酯和油酸盐氧化的捕获率将 为开发一种定量的技术提供关键数据 应用正电子发射计算机断层扫描对心肌脂肪酸氧化率进行区域性评估。

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.