Simultaneous PET imaging of rCBF and dopamine release

rCBF 和多巴胺释放的同步 PET 成像

• 批准号: 6967561
• 负责人: Alexander K Converse
• 金额: $ 17.75万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-19 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6967561
• 关键词: Macaca mulatta; analytical method; blood flow measurement; brain circulation; brain disorder diagnosis; brain imaging /visualization /scanning; diagnosis design /evaluation; dopamine receptor; high performance liquid chromatography; laboratory rat; method development; neurochemistry; neurotransmitter transport; positron emission tomography; radiotracer

DESCRIPTION (provided by applicant): Malfunctions in the dopaminergic system are implicated in a variety of prevalent and debilitating pathologies, e.g. attention deficit disorders, Parkinson's, addiction, and schizophrenia. This project's long-term goal is the development of a positron emission tomography (PET) method that may be applied to better understand dopaminergic neuromodulation at the systems level in the human brain. Such studies would seek to correlate alterations in measures of extracellular dopamine and brain activity in response to stimuli, tasks, or drugs. Because of variation within an individual between scans, it is valuable to simultaneously image dopamine release and changes in regional cerebral blood flow (rCBF). Therefore, this dual tracer method involves a novel protocol for delivering a short lived blood flow tracer, [17F]fluoromethane (t1/2 = 65 s), in the presence of a long lived neurochemical tracer, [11C]raclopride (t1/2 = 20 min). Human studies using this technique would shed light on normal function and mechanisms of disease, and the technique could have diagnostic applications. This project consists of preliminary studies in rats and rhesus monkeys along with simulations of human studies. The specific aims are to (1) develop a tracer delivery protocol and analytical tools based on exploratory studies with rats; (2) optimize the delivery protocols for monkey studies; (3) study the neuromodulatory response to an amphetamine challenge in monkeys, correlating simultaneous observations of alterations in striatal dopamine release and variations in rCBF in various brain regions; and (4) optimize the delivery protocols for human studies based on simulations.

描述（由申请人提供）： 多巴胺能系统的功能障碍与多种流行的、使人衰弱的病症有关，例如，注意力缺陷障碍、帕金森氏症、成瘾症和精神分裂症。该项目的长期目标是开发一种正电子发射断层扫描（PET）方法，可用于更好地了解人脑系统水平的多巴胺能神经调节。此类研究将寻求将细胞外多巴胺测量值的变化与大脑活动对刺激、任务或药物的反应联系起来。由于扫描之间个体内部存在差异，因此同时对多巴胺释放和局部脑血流 (rCBF) 变化进行成像非常有价值。因此，这种双示踪剂方法涉及一种新方案，用于在存在长寿命神经化学示踪剂 [11C]雷氯必利 (t1/2) 的情况下，提供短寿命血流示踪剂 [17F] 氟甲烷 (t1/2 = 65 s) = 20 分钟）。使用这种技术的人体研究将揭示疾病的正常功能和机制，并且该技术可以具有诊断应用。 该项目包括对大鼠和恒河猴的初步研究以及对人体研究的模拟。具体目标是（1）基于大鼠探索性研究开发示踪剂递送方案和分析工具； (2) 优化猴子研究的递送方案； (3) 研究猴子对安非他明激发的神经调节反应，将同时观察到的纹状体多巴胺释放的变化与不同大脑区域的 rCBF 的变化联系起来； (4) 基于模拟优化人体研究的递送方案。