NEW RADIOTRACERS FOR NEUROLOGICAL PET

应用正电子发射计算机断层扫描进一步了解病因和临床表现 神经系统疾病的发展将需要更多 专为神经元的特定方面设计的放射性药物 可能涉及的生物化学。在此项目中，新的 放射性药物被建议用于体内生化研究 在许多神经疾病中可能很重要的过程， 包括帕金森氏症、亨廷顿氏症和阿尔茨海默氏症等 其他。这些新的放射性药物包括 线粒体电子传输链，特别是在复合体I，和 研究放射性示踪剂的形成、浓度或影响 活性氧物种，如自由基。为了研究络合物I，它 建议制备鱼藤酮的正电子发射体标记的衍生物 以及相关的鱼藤类化合物。为了研究自由基，适当地标记了自旋 基于硝酮结构的捕捉剂，如α-苯基-t- 提出了丁基硝酮(PBN)。该项目将承担 这些拟议的新放射性化学物质的体内放射化学合成和 它们的初步动物评估以确定分布、动力学和 新陈代谢。这种新的放射性药物，当可用于PET时 应用，可以用来检验许多最近的假说 发生在大量神经疾病中的潜在生化变化 精神错乱。

Application of PET to the further understanding of the causes and development of neurological diseases will require more radiopharmaceuticals designed for specific aspects of neuronal biochemistry which might be involved. In this Project, new radiopharmaceuticals are proposed for in vivo studies of biochemical processes which may be important in numerous neurological disease, including Parkinson's, Huntington's, and Alzheimer's disease, among others. These new radiopharmaceuticals include markers of the mitochondrial electron transport chain, specifically at complex I, and radiotracers to study the formation of, concentration of or effects of reactive oxygen species such as free radicals. For study of complex I, it is proposed to prepare positron-emitter labeled derivatives of rotenone and related rotenoids. To study free radicals, appropriately labeled spin trapping agents based on the nitrone structure such as alpha-phenyl-t- butyl-nitrone (PBN) are proposed. This Project will undertake the radiochemical synthesis of these proposed new in vivo radiochemicals and their initial animal evaluation to determine distribution, kinetics and metabolism. Such new radiopharmaceuticals, when available for PET applications, could be used to examine numerous recent hypotheses of the underlying biochemical changes occurring in a large number of neurological disorders.