PET: NORMAL CEREBRAL FUNCTION AND AFFECTIVE DISORDERS

我们建议开发和应用发射断层扫描(PET)作为分析 生化分析技术研究正常人脑功能和 情感障碍。目标是：1.)化学/生物化学。 将开发和/或改进快速合成技术 测定用(F-18)-氟和(C-11)脱氧葡萄糖的制备 葡萄糖代谢、C-11和N-13标记氨基酸测定 用于受体分析的蛋白质合成率和F-18配体(主要是 螺哌利多高比活度F-18标记物的研制 可应用于其他配体的技术)。组织生化分析和 在大鼠和猴子身上的放射自显影研究将被用来构建和 定义动力学模型并在不同的蛋白质示踪剂中进行选择 合成和受体分析测量。2.)体层摄影术。NeuroECAT 将被升级以提供前所未有的空间分辨率， 图像质量和量化需要衡量的细节 这项建议所要求的大脑功能的神经解剖学组成部分。 3.)示踪剂动力学建模。测量大脑的运算公式 血流、蛋白质合成、氧代谢和受体分析将 需要开发和验证。4.)正常受试者。研究将会是 用于验证方法，并确定规范和变化 局部葡萄糖和氧代谢、血流和蛋白质合成 费率。将进行研究以确定新陈代谢和血液流量 对特定感觉刺激的反应，以激活视觉，听觉， 语言和认知功能以及这些功能的使用 刺激-反应任务作为情感性精神障碍的激励性测试 病人。5.)病人。局部葡萄糖新陈代谢将在 以确定双相和单相情感障碍患者是否 有可测量的局部生化变化，以建立 功能改变的神经解剖学分布和程度 客观评价所用药物的代谢后果 诊断性(利他林-单相、抑郁症和正常志愿者 对照)和治疗(锂双极)。在基础方面取得成功 对F-18螺哌利多的研究将允许在这些患者中进行研究 研究躁狂/抑郁障碍的多巴胺假说。

We propose to develop and apply emission tomography (PET) as an analytical biochemical assay technique to study normal human cerebral function and affective disorders. The objectives are: 1.) Chemistry/Biochemistry. Rapid synthetic techniques will be developed and/or improved for preparation of (F-18)-fluoro and (C-11) deoxyglucose for measurement of glucose metabolism, C-11 and N-13 labeled amino acids for measurement of protein synthesis rates and F-18 ligands for receptor assays (principally spiroperidol but also development of high specific activity F-18 labeling techniques to be applied to other ligands). Tissue biochemical assay and autoradiographic studies in rats and monkeys will be used to structure and define kinetic models and select among different tracers for protein synthesis and receptor assay measurements. 2.) Tomography. The NeuroECAT will be upgraded to provide unprecedented level of spatial resolution, image quality and quantification necessary to measure the detailed neuroanatomical components of cerebral function required by this proposal. 3.) Tracer kinetic modeling. Operational equations for measuring cerebral blood flow, protein synthesis, oxygen metabolism and receptor assays will be developed and validated. 4.) Normal Subjects. Studies will be performed to validate methods, and to determine norms and variations in local glucose and oxygen metabolism, blood flow and protein synthesis rates. Studies will be carried out to determine metabolic and blood flow responses to specific sensory stimulations to activate visual, auditory, linguistic and cognitive functions and the use of these stimulation-response tasks as provocative tests for affective disorder patients. 5.) Patients. Local glucose metabolism will be measured in patients with bipolar and unipolar affective disorders to determine if there are measurable local biochemical alterations, to establish the neuroanatomical distribution and magnitude of the functional changes and to objectively evaluate the metabolic consequences of drugs administered diagnostically (Ritalin - unipolar, depressed and also normal volunteers as controls) and therapeutically (Lithium - bipolar). Success in basic studies of F-18 spiroperidol will allow studies in these patients to examine the dopamine hypothesis of manic/depressive disorders.