Quantitative PET study of muscarinic receptors in the human brain and its clinical utilization in Alzheimer disease

人脑毒蕈碱受体的定量 PET 研究及其在阿尔茨海默病中的临床应用

• 批准号: 16591239
• 负责人: MIURA Shuichi
• 金额: $ 1.41万
• 依托单位: Research Institute for Brain and Blood Vessels -Akita
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591239/
• 关键词: PET; receptor; NMPB; muscarinic; cholinergic; Binding; Alzheimer; アルツハイマー

Quantification of human brain muscarinic cholinergic receptors was investigated with the use of N-[^<11>C]methyl-3-piperidyl benzilate ([^<11>C]3NMPB) and positron emission tomography (PET). The regional distribution pattern of [^<11>C] 3NMPB was the highest in the striatum ; intermediate in the occipital, temporal and frontal cortices, cingulate gyrus, and thalamus ; lower in the pons ; and lowest in the cerebellum. The binding potential (BP) of [^<11>C] 3NMPB in the brain region was obtained with the use of compartmental models including regional least-squares curve-fitting analyses employing both arterial plasma tracer time-course and radioactivity time-course in the cerebellum as an input function into the brain and uptake ratio of the brain region to cerebellum. The BP estimates obtained with the use of these procedures in all brain regions correlated well with muscarinic receptor densities in the human brain as reported in vitro. Our results indicate the potential for accurate determinations of muscarinic receptor binding in the living human brain with the use of [^<11>C]3NMPB and PET. The mean BP estimates obtained in six patients with Alzheimer disease were lower in all brain regions than in six normal volunteers. However, there was no significant difference between the BP estimates for any brain region in the patients and normal volunteers. This result suggested that muscarinic receptors were kept still in the brain of patient with Alzheimer disease.

用N-[^<11>C]甲基-3-哌啶基二苯甲酸酯（[^<11>C] 3 NMPB）和正电子发射断层扫描（PET）研究了人脑毒蕈碱胆碱能受体的定量。[^ C] 3 NMPB的区域分布模式<11>在纹状体中最高;在枕叶、颞叶和额叶皮质、扣带回和丘脑中居中;在脑桥中较低;在小脑中最低。使用<11>房室模型获得脑区中[^ C] 3 NMPB的结合电位（BP），包括采用小脑中动脉血浆示踪剂时间过程和放射性时间过程作为脑的输入函数和脑区与小脑的摄取比的区域最小二乘曲线拟合分析。在所有脑区使用这些程序获得的BP估计值与体外报告的人脑中的毒蕈碱受体密度相关。我们的研究结果表明，准确测定毒蕈碱受体结合在活的人脑中使用[^<11>C] 3 NMPB和PET的潜力。在6名阿尔茨海默病患者中获得的平均BP估计值在所有脑区均低于6名正常志愿者。然而，在患者和正常志愿者的任何大脑区域的BP估计值之间没有显着差异。提示Alzheimer病患者脑内毒蕈碱受体仍处于静止状态。