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Dopamine D3 Receptor Imaging Agents for PET and SPECT

用于 PET 和 SPECT 的多巴胺 D3 受体显像剂

基本信息

批准号：
7074053
负责人：
ROBERT H MACH
金额：
$ 49.1万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-30 至 2008-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7074053
关键词：
Macaca Sf9 cell line animal tissue bioimaging /biomedical imaging cell line central nervous system disorders dopamine receptor imaging /visualization /scanning laboratory rat positron emission tomography radiotracer receptor binding receptor expression single photon emission computed tomography

项目摘要

DESCRIPTION (provided by applicant): Over the past fifteen years there has been a tremendous amount of research conducted in the development of PET and SPECT radiotracers for studying dopamine D2 receptor function in vivo. This research has been largely driven by the availability of a number of antipsychotics possessing a high affinity for dopamine D2 receptors, and the alteration of D2 receptor density identified in postmortem brain samples from a variety of CNS disorders including schizophrenia, Parkinson's disease, Alzheimer's Disease, and substance abuse. However, the radiotracers that have been developed to date are not capable of discriminating between the different subtypes of the D2-class of receptors. For example, [11C]raclopride and [123I]IBZM bind with high affinity to dopamine D2 and D3 receptors, and [11C/18F]N-methylspiperone binds potently to D2, D3 and D4 receptors. Therefore, measurement of "D2 receptor binding potential" obtained with these radiotracers consists of a composite of D2, D3, and, in the case of N-methylspiperone, D4 receptor density. Within the D2-class of receptors, a great deal of experimental evidence suggests that the D3 receptor plays a critical role in a number of CNS disorders. Furthermore, a number of recent studies suggest that there are differences in the regulation of D2 and D3 receptors in schizophrenia, Parkinson's disease, and cocaine abuse. Therefore, the development of radiotracers having a high affinity for D3 versus D2 receptors, and vice versa, would be of tremendous interest to the PET and SPECT research community. Over the past six years, our group has synthesized a number of heterocyclic and benzamide analogues having a high affinity and modest selectivity for D2 versus D3 receptors. The function of this R21/R33 research project is to develop PET and SPECT radiotracers, selective for the D3 receptor, based on these lead compounds. The goal of the R21 component of this project is to synthesize and characterize in vitro putative PET and SPECT radiotracers. Once potential radiotracers are identified, a series of detailed in vitro and in vivo studies will be conducted in the R33 Phase of the project as part of the ligand validation process. The goal of this research project is to develop one PET and one SPECT radiotracer that can be used in functional imaging studies of the D3 receptor in vivo. A secondary goal of this project is to develop an iodine-125 labeled radiotracer for in vitro binding studies of the D3 receptor.

描述（由申请人提供）：在过去的十五年中，在研究体内多巴胺D2受体功能的PET和SPECT放射性示踪剂的开发方面进行了大量的研究。这项研究在很大程度上是由于一些对多巴胺D2受体具有高亲和力的抗精神病药物的可用性，以及在各种中枢神经系统疾病（包括精神分裂症、帕金森病、阿尔茨海默病和药物滥用）的死后脑样本中发现的D2受体密度的改变。然而，迄今为止开发的放射性示踪剂无法区分d2类受体的不同亚型。例如，[11C]raclopride和[123I]IBZM对多巴胺D2和D3受体具有高亲和力，[11C/18F] n -甲基spiperone对D2、D3和D4受体具有强亲和力。因此，用这些放射性示踪剂测量的“D2受体结合电位”由D2、D3和n -甲基spiperone的D4受体密度组成。