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

痴呆症的神经生物学研究。

基本信息

批准号：
05454297
负责人：
FUKUDA Hiroshi
金额：
$ 4.1万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

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.

为了使痴呆症患者的乙酰胆碱神经传递障碍可视化，今年进行了以下研究。(1)乙酰胆碱受体显像：用乙酰<11>胆碱受体的配体--采用连续动脉采血，用HPLC法测定血浆中未代谢的放射性配体的含量，用PET图像和血浆输入函数，用Patlak图分析估算局部脑的受体结合电位。然后，使用解剖标准化系统（HBA）将这些数据转换成标准脑格式，并计算结合容量的平均值和标准偏差。为了进一步发展，正在进行这种配体在老年正常人和痴呆症患者中的PET研究。(2)脑中乙酰胆碱酯酶（AchE）活性的估计：我们设计的N-甲基-3-哌啶基酯作为AchE的底物，在酶的代谢变化后被困在脑中。我们已经开发并建立了化合物的C-11标记。进行了动物急性毒性试验和MIRD程序的辐射剂量估计，并获得了伦理委员会的授权，将该放射性示踪剂用于人类。然后，首先在正常受试者中使用该示踪剂进行脑的PET成像。还进行了动脉血样采集和血浆代谢物分析。使用PET图像和血浆输入函数，正在开发用于测量脑中AchE活性的数学模型。目前，正常人和痴呆患者的PET研究正在进行中。