CONCENTRATION OF DOPAMINE TRANSPORTERS TO BMAX OR NOT TO BMAX ?

多巴胺转运蛋白浓度达到 BMAX 还是不达到 BMAX？

• 批准号: 6453807
• 负责人: EVAN MORRIS
• 金额: $ 11.11万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6453807
• 关键词: Mammalia; behavioral /social science research tag; bioimaging /biomedical imaging; nervous system; pharmacology; positron emission tomography; proteins; psychology; radiology; substance abuse related disorder

The dopamine transporter is increasingly recognized as a window on the status of dopamine neurons Dopamine transporter levels decline in tandem with the loss of dopamine in Parkinson's disease and in experimentally produced parkinsonism The dopamine transporter is also a principal target of Ritalin , Zyban and cocaine in brain Although it is feasible to accurately measure the density of the transporter in post-mortem tissue, measures of transporter density in living brain by PET or SPECT imaging are more challenging With PET imaging in non-human primate brain, we measured transporter levels using a technique of three injections of [11C]CFT (WIN 35,428) followed by non-linear least-squares (NLSQ) fitting of all the dynamic data simultaneously The resulting data yielded a value for B'max which does not correspond closely to B'max/Kd The advantages of the three-injection model is the feasibility of measuring B'max and Kd (Koff/Kon) separately It is inadvisabl e to use B'max/Kd or distribution volume ratio (DVR) in all circumstances as an indicator of B'max as the underlying assumption for generating binding potential is the constancy of Kd For receptor imaging, agonist drugs can convert receptors from high to low affinity, thereby reducing the apparent Kd for PET imaging agents that are either agonists or partial agonists Kd may also differ as a function of other factors, including age, pathological states, mutations in receptors, or modifications of the membrane matrix of protein targets If feasible, it seems imprudent to sacrifice the possibility of obtaining accurate data with measures of Kd and B'max

多巴胺转运蛋白越来越被认为是一个窗口 多巴胺神经元的状态 多巴胺转运蛋白水平下降 与帕金森病和多巴胺的丧失同时发生 实验产生的帕金森症多巴胺转运蛋白也是 利他林、载班和可卡因在大脑中的主要目标 准确测量运输体的密度是可行的 死后组织，通过测量活体大脑中的转运蛋白密度 PET 或 SPECT 成像更具挑战性 非人类灵长类动物大脑，我们使用 三次注射 [11C]CFT (WIN 35,428) 的技术，然后 所有动态数据的非线性最小二乘 (NLSQ) 拟合 同时得到的数据产生了 B'max 的值，它确实 与 B'max/Kd 不太对应 的优点 三注射模型测量B'max和Kd的可行性 (Koff/Kon) 单独使用 B'max/Kd 或 所有情况下的分配容积比（DVR）作为指标 B'max 作为产生结合势的基本假设 是 Kd 的恒定性 对于受体成像，激动剂药物可以转换 受体从高亲和力到低亲和力，从而降低表观 Kd 对于激动剂或部分激动剂 Kd 的 PET 显像剂 也可能因其他因素而有所不同，包括年龄、 病理状态、受体突变或修饰 蛋白质靶标的膜基质 如果可行，似乎不明智 牺牲了通过以下措施获得准确数据的可能性 Kd 和 B'max