NEW RADIOTRACERS FOR NEUROLOGICAL PET

用于神经宠物的新型放射示踪剂

• 批准号: 6204995
• 负责人: MICHAEL R KILBOURN
• 金额: $ 10.35万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6204995
• 关键词: Macaca nemestrina; bioimaging /biomedical imaging; brain metabolism; carbon; chemical synthesis; drug adverse effect; drug metabolism; drug screening /evaluation; electron transport; fluorine; free radical oxygen; gerbil /jird; laboratory mouse; laboratory rat; neurochemistry; neuromuscular disorder diagnosis; oxidative stress; pharmacokinetics; plant insecticide; positron emission tomography; radionuclides; radiopharmacology; radiotracer

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.

将宠物应用于进一步理解原因和 神经疾病的发展将需要更多 用于神经元特定方面的放射性药物 可能涉及的生物化学。在这个项目中，新 提出了用于生化的体内研究的放射性药物 在许多神经系统疾病中可能很重要的过程， 包括帕金森氏症，亨廷顿和阿尔茨海默氏病 其他的。这些新的放射性药物包括 线粒体电子传输链，特别是在复合物I处， 放射性示例研究的形成，浓度或影响 活性氧，例如自由基。为了研究复杂的I 提议准备葡萄干酮标记为标记的衍生物 和相关的棒棒。要研究自由基，请适当标记为自旋 基于硝基结构的捕获剂，例如α-苯基-T- 提出了丁基 - 硝酸（PBN）。该项目将承担 这些提出的新的体内放射化学物质的放射化合物合成和 他们最初的动物评估以确定分布，动力学和 代谢。这种新的放射性药物，如果可以供宠物 应用可用于检查众多最近的假设 在大量神经系统中发生的基本生化变化 疾病。