Pet Imaging of Extrastriatial Dopamine Levels

纹状体外多巴胺水平的宠物成像

• 批准号: 6678142
• 负责人: ROBERT MICHAEL KESSLER
• 金额: $ 16.99万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-10 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6678142
• 关键词: bioimaging /biomedical imaging; clinical research; corpus striatum; dextroamphetamine; dopamine; dopamine receptor; fluorine; human subject; limbic system; method development; neurochemistry; neurotransmitter transport; positron emission tomography; radionuclides; radiotracer; substantia nigra; thalamus; young adult human (21-34)

DESCRIPTION (provided by applicant): Dopaminergic neurotransmission in cortex, limbic regions and thalamus is believed to be centrally involved in the pathophysiology of schizophrenia, psychostimulant drug abuse, and attention deficit disorder. While there are PET and SPECT methods for evaluating striatal dopamine (DA) release and baseline extracellular DA levels in man, at present there are no well validated methods for studying DA release and baseline extracellular DA levels in extrastriatal regions in man. [18F] fallypride is an extremely potent and selective dopamine D2 radioligand, i.e., a KD of 31 pM for the dopamine D2 receptor, which can be used do delineate and quantitate striatal, thalamic, limbic and cortical dopamine D2 receptors in man. Studies in primates demonstrate that [18F] fallypride is sensitive to levels of d-amphetamine released dopamine in both striatum and extrastriatal regions. We propose to perform [18F] fallypride PET studies in 12 normal subjects (ages 18-40, 6M, 6F) prior to and following d-amphetamine administration (0.43mg/kg orally) to study d-amphetamine induced dopamine release in extrastriatal regions. This dose of real d-amphetamine produces decrements in striatal [11C] raclopride binding potentials similar to those seen with a 0.2-0.3 mg/kg IV dose of d-amphetamine with similar variability, but with fewer and less severe side effects. We propose to perform additional [18F] fallypride PET studies in 12 normal subjects (ages 18-40, 6M, 6F) prior to and following a 36-hour course of 56.6 mg/kg alphamethylparatyrosine/24 hours (6 grams over 36 hours for a 70 kg subject) to estimate baseline extracellular dopamine levels in extrastriatal regions. The development of methods for estimating DA release and baseline extracellular DA levels in extrastriatal regions will allow important new research studies in a number of psychiatric and neurological disorders which may allow design and evaluation of new therapeutic interventions.

描述（由申请人提供）：皮质、边缘区和丘脑中的多巴胺能神经传递被认为是精神分裂症、精神兴奋剂药物滥用和注意力缺陷障碍的病理生理学的中心环节。 虽然有PET和SPECT方法用于评估纹状体多巴胺（DA）的释放和基线细胞外DA水平的人，目前还没有得到充分验证的方法，研究DA释放和基线细胞外DA水平的人纹状体外区域。 [18F]Fallypride是一种非常有效和选择性的多巴胺D2放射性配体，即，对多巴胺D2受体的KD为31 pM，其可用于描绘和定量人的纹状体、丘脑、边缘系统和皮质多巴胺D2受体。我们建议在12名正常受试者（年龄18-40岁，6 M，6 F）中进行[18F] fallypride PET研究，在d-苯丙胺给药（口服0.43mg/kg）之前和之后，研究d-苯丙胺诱导的纹状体外区域多巴胺释放。该剂量的真实的d-苯丙胺使纹状体[11 C]雷氯必利结合电位降低，与静脉注射0.2-0.3 mg/kg d-苯丙胺所观察到的相似，具有相似的变异性，但副作用较少且不太严重。我们建议在12名正常受试者（年龄18-40岁，6 M，6 F）中进行额外的[18F] fallypride PET研究，在36小时的56.6 mg/kg α-甲基对酪氨酸/24小时（70 kg受试者在36小时内服用6 g）疗程之前和之后，以估计纹状体外区域的基线细胞外多巴胺水平。估计纹状体外区DA释放和基线细胞外DA水平的方法的发展将允许在一些精神和神经系统疾病，这可能允许设计和评估新的治疗干预措施的重要的新的研究。