PET STUDY OF BIOCHEMISTRY AND METABOLISM OF THE CNS

我们建议在密歇根大学建立一个设施， 一种新的，非侵入性的方法来研究人类大脑利用正电子 发射代谢和药理学探针。 一个专用的医用回旋加速器， “头部只有”正电子发射断层扫描仪，并扩大 放射性化学/放射性药物设施将补充现有的核 医疗设施。 拟议的研究涉及使用已建立的正电子发射探针， 13 N-氨、11 C或18 F-2-脱氧葡萄糖和11 C-缬氨酸，用于研究代谢 与亨廷顿病、癫痫发作障碍、内耳疾病和 镰状细胞性贫血导致的中风 我们还将调查 与中风相关的瘫痪的低张和高张阶段。 还将合成新的正电子发射放射性药物。 18F-缬氨酸 和相关的氨基酸将最初用于评估大脑 蛋白质合成的苯丙酮尿症，然后将扩展到研究 与本项目相关的其他条件。 惰性卤代烃 将用于可视化相关可行性中的脑白色物质 多发性硬化症和白色梗死患者的研究。 胆碱能和多巴胺能受体的探针，11 C-奎宁环二苯乙酸酯， 11 C-螺哌利多和相关的类似物被提出与 关于亨廷顿病的研究

We propose to establish a facility at University of Michigan for the development of a new, non-invasive approach to human brain research utilizing positron emitting metabolic and pharmacologic probes. A dedicated medical cyclotron, a "head only" positron-emission tomographic scanner, and expanded radiochemical/radiopharmaceutical facilities will complement an existing nuclear medicine facility. Proposed studies have involved the use of established positron-emitting probes, 13N-ammonia, 11C or 18F-2-deoxyglucose, and 11C-valine, to study metabolic correlates of Huntington's disease, seizure disorders, inner ear disease, and strokes resulting from sickle cell anemia. We will also investigate the hypotonic and hypertonic phases of paralysis associated with stroke. New positron-emitting radiopharmaceuticals will also be synthesized. 18F-valine and related amino acids will be used initially for the evaluation of brain protein synthesis in phenylketonuria and then will be extended to the study of other conditions associated with this project. Inert halogenated hydrocarbons will be employed to visualize brain white matter in associated feasibility studies from multiple sclerosis and patients with white matter infarctions. Probes of cholinergic and dopaminergic receptors, 11C-quinuclidinyl benzilate, 11C-spiroperidol, and related analogs, are proposed in connection with the studies on Huntington's disease.