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PET measurement system as a biomarker of central nervous system pharmacological effect of drugs.

PET测量系统作为药物中枢神经系统药理作用的生物标志物。

基本信息

批准号：
16390350
负责人：
SENDA Michio
金额：
$ 9.02万
依托单位：
Institute of Biomedical Research and Innovation
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

PET is useful for evaluating pharmacological effect of drugs although only a few clinical trials have been conducted in Japan due to poor environment both in technologies and regulations. We have established the so-called in-house GMP-based quality control according to the guidelines issued by the Japan Radioisotope Association (Version 2001) in the Institute of Biomedical Research and Innovation. An imaging CRO specializing in PET was established locally to support clinical trials using PET. An in-house license for the PET research nurse has also been established. Using these systems, a clinical study was conducted regarding PET measurement of the central nervous system pharmacological effect of a drug. Some antihistamines have a sedative effect as they enter the brain and block the histamine H1 receptor, which is difficult to evaluate in behavioral tests due to large variation but can be measured as H1 receptor occupancy using PET with C-11 labeled doxepin. Olopatadine is a slightly sedative antihistamine, but the sedative effect wears off after repeated medication. In the present study, H1 receptor binding potential (BP) was measured with PET on 17 subjects with perennial nasal allergy at baseline, at the initial dose of olopatadine, and at another dose after repeated administration of olopatadine for four weeks. The BP of the frontal cortex under the initial single dose was slightly lower than the baseline, but it showed a marked decrease following 4-week medication, which suggests down regulation of H1 receptor possibly due to increased endogenous histamine level and may be related to the wearing off phenomenon. The results indicate that it is possible and plausible to evaluate the central nervous system effect of a drug and its repeated administration on the receptor using PET, which may be useful for drug development.

PET可用于评价药物的药理作用，但由于技术和法规环境差，在日本仅进行了少数临床试验。根据日本放射性同位素协会（2001年版）在生物医学研究和创新研究所发布的指南，我们建立了所谓的基于GMP的内部质量控制。在当地建立了专门从事PET的成像CRO，以支持使用PET的临床试验。PET研究护士的内部许可证也已建立。使用这些系统，进行了关于药物的中枢神经系统药理作用的PET测量的临床研究。一些抗组胺药具有镇静作用，因为它们进入大脑并阻断组胺H1受体，这是难以在行为测试中评估，由于大的变化，但可以使用PET与C-11标记的多塞平作为H1受体占有率测量。奥洛他定是一种轻微的镇静抗组胺药，但反复用药后镇静作用消失。在本研究中，采用PET测量了17例常年性鼻过敏受试者的H1受体结合潜力（BP），这些受试者分别处于基线、奥洛他定初始剂量和奥洛他定重复给药4周后的另一个剂量。首次单次给药时额叶皮质BP略低于基线，但给药4周后出现明显下降，提示H1受体下调可能是由于内源性组胺水平升高，可能与消退现象有关。结果表明，这是可能的和合理的评价中枢神经系统的影响，药物和重复给药的受体使用PET，这可能是有用的药物开发。

项目成果

期刊论文数量（27）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Performance characteristics of a new 3-dimensional continuous-emission and spiral-transmission high-sensitivity and high-resolution PET camera evaluated with the NEMA NU 2-2001 standard.

根据 NEMA NU 2-2001 标准评估的新型 3 维连续发射和螺旋传输高灵敏度和高分辨率 PET 相机的性能特征。

DOI：
发表时间：
2006
期刊：
J Nucl Med 47(1)
影响因子：
0
作者：
Matsumoto K;Kitamura K;Mizuta T;Tanaka K;Yamamoto S;Sakamoto S;Nakamoto Y;Amano M;Murase K;Senda M
通讯作者：
Senda M

Investigation of single, random, and true counts from natural radioactivity in LSO-based clinical PET

DOI：
10.1007/bf03027389
发表时间：
2005-04-01
期刊：
ANNALS OF NUCLEAR MEDICINE
影响因子：
2.6
作者：
Yamamoto, S;Horii, H;Senda, M
通讯作者：
Senda, M

断層撮影装置、それを備えた撮影システム並びに撮影データ取得方法

层析成像装置、配备有该装置的成像系统以及成像数据获取方法

DOI：
发表时间：
2007
期刊：
影响因子：
0
作者：
通讯作者：

Accuracy of image fusion using a fixation device for whole-body cancer imaging.

DOI：
10.2214/ajr.184.6.01841960
发表时间：
2005-06
期刊：
AJR. American journal of roentgenology
影响因子：
0
作者：
Y. Nakamoto;S. Sakamoto;T. Okada;K. Matsumoto;Eiri Minota;H. Kawashima;M. Senda
通讯作者：
Y. Nakamoto;S. Sakamoto;T. Okada;K. Matsumoto;Eiri Minota;H. Kawashima;M. Senda

Severe haemodynamic stress in selected subtypes of patients with moyamoya disease: a positron emission tomography study