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

点击翻译按钮获取中文摘要

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.