The development for novel positron-labeled radiopharmaceuticals and their application to measurement of the cerebral functions

新型正电子标记放射性药物的研制及其在脑功能测量中的应用

基本信息

批准号：
11694234
负责人：
YANAI Kazuhiko
金额：
$ 12.47万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

Positron emission tomography (PET) is a unique method to examine brain chemistry non-invasively in humans. Using PET techniques, specific neurochemical systems, such as dopaminergic and histaminergic neuronal systems, were measured in the living human brain. Specific ^<11>C- or ^<18>F-labelled radiotracers for selective labeling of several receptors were newly synthesized by new synthetic methods. We also developed several new methods of imaging in the human brain using 3-demensional PET system. Our developed PET methods for human neuropharmacology are as follows : Non-invasive measurement of receptor binding parameters ; cerebral activation study with H_2^<15>O and 3D-PET ; ^<11>C-ligand activation study to measure neurotransmitter release. As for pharmacological applications, we used PET techniques for evaluating sedative properties of antihistamines. Antihistamines are the efficacious drugs to be used for the symptomatic relief of allergic diseases. The safety issue of antihistamine … More s is of central importance because of their widespread use in current medical practice. PET was used to better understand the pharmacological effects of antihistamines on the central nervous system. The H1 receptor occupancy was examined in young male volunteers with [^<11>C]-doxepin (a potent H1 antagonist) after the oral or intravenous administration of antihistamines. In other studies, the cognitive performance was also measured tachistoscopically before and after taking antihistamines. The H1 receptor occupancy in the human frontal cortex caused by antihistamines is significantly correlated with the reported values of incidence of sleepiness in clinical trials, and the occupancy is well proportional to the impaired cognitive performance. To understand the brain mechanism of antihistamine-induced "sleepiness and impaired cognition", the regional cerebral blood flow (rCBF) during the task was measured using 3D-PET and H_2^<15>O before and after administration of d-chlorpheniramine. After its administration, the rCBF was significantly decreased on the bilateral middle temporal gyrus, midbrain and anterior cingulate. These findings suggest that H1 receptor blockade would be affected on the activity of the attention and cognitive system in the brain. Less

正电子发射断层扫描（PET）是一种独特的方法，可以在人类中非侵入性地检查脑化学。使用PET技术，在活的人脑中测量了特定的神经化学系统，例如多巴胺能和组胺能神经元系统。特定的 ^<11> c-或 ^<18> f标记的放射性示例用于选择性标记几种受体，新合成方法是新合成的。我们还使用三维宠物系统开发了几种在人脑中成像的新方法。我们开发的人类神经药理学的PET方法如下：受体结合参数的非侵入性测量； H_2^<15> O和3D-PET的脑激活研究； ^<11> C-配体激活研究，用于测量神经递质释放。至于药物应用，我们使用PET技术来评估抗组胺药的镇静特性。抗组胺药是用于症状缓解过敏性疾病的有效药物。抗组胺药的安全问题……更多的S是至关重要的，因为它们在当前的医学实践中使用了宽度。 PET被用来更好地了解抗组胺药对中枢神经系统的药物作用。在口服或静脉注射抗组胺药后，在患有[^<11> c] -doxepin（潜在的H1拮抗剂）的年轻男性志愿者中检查了H1受体占用率。在其他研究中，在服用抗组胺药之前和之后，还通过速度镜进行了认知性能。由抗组胺药引起的人额叶皮层中的H1受体占用与临床试验中的嗜睡值显着相关，并且占用率与认知性能受损成正比。为了了解抗组胺药诱导的“嗜睡和认知受损”的大脑机制，使用3D-PET和H_2^<15> O测量了在任务过程中脑血流量（RCBF）。给药后，在双侧中部回，中脑和前扣带回上，RCBF显着降低。这些发现表明，H1受体阻滞将受到大脑注意力和认知系统的活性的影响。较少的