TECHNETIUM-99M LABELED FATTY ACID ANALOGS FOR IMAGING

这项研究计划的目标是开发一种广泛的 用于检测患者心肌代谢变化的临床试剂 单光子发射计算机断层扫描与~（99）Tc标记脂肪 本申请中提出的酸。拟议的研究将确定 ~（99）Tc标记脂肪酸的最佳结构特征 核医学心肌显像剂的研制。Tc-99 m标记 将合成脂肪酸并在大鼠中研究其心肌摄取。 用~（99）Tc ~（99）m标记三个系列的脂肪酸， 将制备关于亲脂性和羧基位点的化合物，并且它们的 通过制备其类似物来鉴定化学结构。这些 脂肪酸类似物利用1，2-二硫杂-5，8-二氮杂环癸烷和 “3+1”原则作为锝螯合基团。它们被设计成 通过长链脂肪酸载体蛋白转运到心肌细胞 天然脂肪酸的作用机制。脂肪酸衍生物将是 设计成不能被完全分解代谢。以这种方式 在示踪剂被“捕获”之后， 细胞内。这些研究将确定这类药物的潜力。 用于评价脂肪酸区域差异的放射性药物 在缺血性心脏病和心肌病中发生的代谢。 拟议商业应用：不可用

The objective of this proposed research plan is to develop a widespread clinical agent for detecting myocardial metabolic changes in patients using single photon emission computed tomography and technetium99m labeled fatty acids proposed in this application. The proposed research will determine the optimal structure features of technetium-99m labeled fatty acid for the development of a myocardial imaging agent for nuclear medicine. Tc-99m-labeled fatty acids will be synthesized and their myocardium uptake studied in rats. Three series of fatty acids labeled with Tc-99m at different positions with respect to the lipophilic and carboxylic sites will be prepared and their chemical structure identified by preparation of their rhenium analogs. These fatty acid analogs utilize both the 1,2-dithia-5,8-diazacyclodecan and the '3+1' principle as the technetium chelating moieties. They are designed to be transported into myocardial cells by the long chain fatty acid carrier protein mechanism used by natural fatty acids. The fatty acid derivatives will be designed such that they cannot be completely catabolized. In this manner transport/delivery and metabolism can be imaged after the tracer is 'trapped' intracellularly. These studies will determine the potential of this class of radiopharmaceuticals for evaluation of region discrepancies in fatty acid metabolism which occur in ischemic heart disease and cardiomyopathies. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE