Neurobiological Study for Demintia. -In vivo analysis of human brain using PET.

为了解痴呆患者的乙酰胆碱神经递质障碍，本研究开展了以下研究：(1)乙酰胆碱受体显像：对6例正常人进行了正电子发射断层扫描(正电子发射断层扫描)。连续采集动脉血，用HPLC测定血浆中未代谢的放射性配基的比例，利用PET图像和血浆输入函数进行Patlak图分析，估计局部脑内受体结合电位。然后，使用解剖标准化系统(HBA)将这些数据转换为标准脑格式，并计算结合容量的平均值和标准差。为了进一步发展，在老年正常人和痴呆患者中使用该配体的PET研究仍在进行中。(2)脑内乙酰胆碱酯酶(AChE)活性的估计：我们设计的作为AChE底物的N-甲基-3-哌酯在酶的代谢变化后被捕获在大脑中。我们已经开发并建立了该化合物的C-11标记。进行了动物的急性毒性和MIRD程序的辐射剂量估算，该放射性示踪剂在人类中的使用得到了伦理委员会的授权。然后，首先在正常受试者中使用这种示踪剂对大脑进行PET成像。还进行了动脉血采样和血浆代谢物分析。利用PET图像和血浆输入函数，正在开发用于测量大脑AchE活性的数学模型。现在，对正常受试者和痴呆症患者的PET研究正在进行中。

In order to visualize acetylcholine neurotransmission disorders in demented patients, the following studies were performed in this year.(1) Imaging for acetylcholine receptors : positron emission tomography (PET) with ^<11>C-benztropin, a ligand for acetylcholine receptors, were performed in 6 normal subjects. Serial arterial blood sampling was performed and the fraction of unmetabolized radio-ligand in plasma was measured by HPLC.Receptor binding potential in regional brain was estimated by Patlak plot analysis using PET images and plasma input function. Then, these data were transformed into standard brain format using anatomical standardization system (HBA) and mean and standard deviation of the binding capacity were calculated. For further development, PET studies with this ligand in aged normals and demented patients were going on.(2) Estimation of acetylcholine esterase (AchE) activity in the brain : N-methyl-3-piperidyl ester, which we have designed as a substrate for AchE,is trapped in the brain after metabolic change by the enzyme. We have developed and established C-11 labeling of the compound. Acute toxicity in the animals and radiation dose estimation by MIRD procedure were performed, and use of this radiotracer for humans was authorized by ethical committee. Then, PET imaging of the brain with this tracer was firstly performed in a normal subject. Arterial blood sampling and analysis of metabolites in the plasma was also performed. Using PET images and plasma input function, mathematical modeling for the measurement of AchE activity in the brain were under developing. Now PET studies in normal subject and demented patients were going on.