Research on Brain Function through in vivo Neuroreceptor Study Using Positron Emission Tomography

为了阐明脑功能的机制，我们检测了脑内不同受体系统的受体结合情况，得到以下结果.使用C-11 SCH 23390作为多巴胺D1配体，我们建立了一种方法，用于定量的结合能力，使用正电子发射断层扫描（PET）。在健康志愿者中测量结合能力，并且在纹状体和额叶皮质中观察到与年龄相关的结合减少。在情绪障碍患者中也测量了结合，并且仅在额叶皮质中观察到结合的减少，而不在纹状体中。C-11 Ro 15 -1788是中枢型苯二氮卓受体的配体，在有或没有非放射性载体的情况下，被给予正常志愿者。利用PET测定的特异性结合值和血清游离配体活性进行体内Scachard分析，计算人脑中苯二氮卓类受体的Bmax和KD值.我们开发了C-11 benztropin作为乙酰胆碱受体的配体。使用PET进行示踪剂的第一次成像研究。纹状体和丘脑中的放射性较高，受体密度较高。另一方面，小脑中的放射性，其中受体密度低。利用图像数据和血清中游离配体的活性，正在开发一种定量方法.用加速老化小鼠（SAM）测定了苯二氮卓受体结合与年龄的关系。在对照R/1系中观察到与皮质的结合的α-受体相关的减少，而在俯卧P/8系中未观察到这种减少。

In order to make clear the mechanisms of brain function,we examined the receptor binding in various receptor system in the brain and obtained the following results.1. Using C-11 SCH23390 as a dopamine D1 ligand,we established a method for quantification of binding capacity using positron emission tomography (PET). The binding capacity was measured in healthy volunteers and age-related decrease of the binding was observed both in the striatum and frontal cortex. The binding was also measured in patients with mood disorders and decrease of the binding was observed only in the frontal cortex but not in the striatum.2. C-11 Ro15-1788, a ligand of central type benzodiazepine receptor, was administered to normal volunteers with or without non-radioactive carrier. In vivo Scachard analysis was made using the value of specific binding measured by PET and serum activity of free ligand and Bmax and KD value of benzodiazepine receptor in the human brain was calculated.3. We developed C-11 benztropin as a ligand of acetylcholine receptor. The first imaging study with the tracer was performed using PET. The radioactivity was high in the striatum and thalamus, where receptor density was high. On the other hand, the radioactivity in the cerebellum, where receptor density was low. Using the image data and serum activity of free ligand, a method of quantification is under developing.4. Binding of benzodiazepine receptor was measured in senile accelerated mouse (SAM) in relation to increasing of age. Age-related decrease of the binding to the cortex was observed in control R/1 line, whereas the decrease was not observed in prone P/8 line.