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

为了弄清脑功能的机制，我们检测了脑内各种受体系统中的受体结合情况，得到了以下结果。以C-11SCH23390为多巴胺D1配体，建立了正电子发射断层扫描(PET)定量测定结合容量的方法。测量了健康志愿者的结合能力，观察到纹状体和额叶皮质的结合能力随着年龄的增长而降低。在有情绪障碍的患者中也测量了这种结合，仅在额叶皮质观察到结合的减少，而在纹状体中没有观察到。C-11Ro15-1788是中枢型苯二氮卓类受体的配基，分别在非放射性载体和非放射性载体下给药。用PET测得的特异性结合值进行体内Scachard分析，计算血清游离配体活性和人脑组织苯二氮卓类受体的Bmax和Kd值。我们开发了C-11苯妥拉平作为乙酰胆碱受体的配体。示踪剂的第一次成像研究是使用PET进行的。纹状体和丘脑的放射性较高，受体密度较高。另一方面，受体密度低的小脑中的放射性。利用图像数据和血清游离配体的活性，正在开发一种定量的方法。在衰老加速小鼠(SAM)上测定了苯二氮卓类受体结合与增龄的关系。在对照R/1系中观察到与皮质结合的年龄相关性减少，而在倾向的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.