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.

使用N - [^<11> c]甲基-3-二哌啶苯甲酸酯（[^<11> c] 3NMPB）和正电子发射断层扫描（PET）的N - [^<11> c]使用N - [^<11> c]甲基-3-二哌啶基（PET），研究了人脑毒蕈碱胆碱能受体的定量。 [^<11> c] 3nmpb的区域分布模式在纹状体中是最高的。枕骨，颞和额叶皮层，扣带回和丘脑中的中间；庞斯较低；小脑中最低。通过使用隔室模型（包括区域最小二乘曲线拟合分析），在大脑区域的[^<11> c] 3NMPB的结合势（BP）获得了使用动脉等离子体示踪性的时间课程和放射性时间顺序的分析，并在小脑中作为对大脑和脑部的脑部的输入功能，以凝视大脑的脑部。如在体外报道的那样，在所有大脑区域中使用这些程序获得的BP估计与人脑中的毒蕈碱受体密度良好相关。我们的结果表明，使用[^<11> c] 3nmpb和PET的[^<11> c]和PET的[^<11> c]使用[^<11> c]和PET的生物中的毒蕈碱受体结合的潜力。在所有大脑区域中，六名阿尔茨海默氏病患者获得的平均BP估计值低于六名正常志愿者。但是，患者和正常志愿者的任何大脑区域的BP估计之间没有显着差异。该结果表明，毒蕈碱受体仍在患有阿尔茨海默氏病的患者的大脑中。