Core--Brain imaging

在本CCNMD的介绍中回顾的大量证据表明，离散脑区5-羟色胺（5-HT）神经传递的改变使自杀行为变得脆弱。最近开发的方法，以评估5-羟色胺在体内的神经传递PET允许直接测试这一假设的患者。脑成像核心是一个由来自不同学科（化学，药理学，物理学，数学）的科学家组成的综合团队，涵盖了开发和支持PET神经受体研究所需的专业知识。脑成像中心为中心提供的服务分为四大类：1）为中心的脑成像项目提供后勤支持和技术专业知识。核心提供研究设计、实施和分析水平的专业知识。此外，这些研究还受益于堆芯维护的一般基础设施，如放射化学实验室和图像分析工作站。2)为其他堆芯提供化学和放射化学服务，如氚化配体或其他商业上无法获得的化合物。3)为年轻的研究人员提供脑成像方面的培训。这些包括PGF-IV至VI居民，他们正在完成脑成像部的研究金，以及该中心的其他研究人员，他们有兴趣将脑成像技术应用于情绪障碍和自杀的研究。4)开发与自杀研究相关的新的成像模式。在接下来的五年里，我们的开发工作将针对5-羟色胺（5-HT）系统与PET。这些目标的选择是由背景部分中提供的与自杀易感性相关的神经化学失衡的一般模型指导的。1)开发并验证使用放射性标记拮抗剂[11 C] DL 100907测量人体中5-HT/2A受体结合潜力; 2）开发一种新的放射性示踪剂，用于使用PET测量5-HT/1B受体（[11C]GR127935）; 3）研制一种新的5-HT/1A受体激动剂，用于测定5-HT/1A受体激动剂的高亲和力状态（[11 C]MHA），并基于内源性竞争技术用该配体开发5-HT释放的测量; 4）开发放射性标记的激动剂以测量5-HT/2A受体的高亲和力状态（[123 I]/[11 C]DOI）。总之，这些项目应提供新的和复杂的工具，在体内的5-羟色胺神经传递的患者有自杀企图的历史特征。中心在本资助周期开发的放射性示踪剂将在下一资助周期用于临床研究。

Numerous lines of evidence reviewed in the introduction of this CCNMD suggest that alterations of serotonin (5-HT) neurotransmission in discrete brain areas confer vulnerability to suicidal behavior. Recent development of methods to assess 5-HT neurotransmission in vivo with PET allows direct testing of this hypothesis in patients. The brain imaging core is an integrated team of scientists from various disciplines (chemistry, pharmacology, physics, mathematics), covering the range of expertise needed to develop and support PET neuroreceptor studies. The services provided to the Center by the brain imaging core fall into four general categories: 1) To provide logistical support and technical expertise to brain imaging projects of the Center. The core provides expertise at the level of study design, implementation, and analysis. In addition, these studies benefit from the general infrastructure maintained by the core, such as radiochemistry laboratories and image analysis workstations. 2) To provide chemistry and radiochemistry services to other cores, such as tritiated ligands or other compounds not available commercially. 3) To provide training in brain imaging to young investigators. These include PGF-IV to VI residents, who are completing a fellowship in the Brain Imaging Division, as well as other investigators in the Center, interested in applying brain imaging techniques to the study of mood disorders and suicide. 4) To develop new imaging modalities that are pertinent to suicide research. Over the next five years, our development effort will be targeted at the serotonin (5-HT) system with PET. The choice of these objectives is guided by a general model of neurochemical imbalance associated with suicide vulnerability provided in the background section. 1) To develop and validate a measure of 5HT/2A receptors binding potential in humans using the radiolabeled antagonist [11C],DL 100907; 2) To develop a new radiotracer to measure 5-HT/1B receptors with PET ([11C]GR127935); 3) To develop a new radiolabeled agonist to measure the agonist high affinity state of the 5-HT/1A receptors ([11C]MHA) and to develop with this ligand a measure of 5-HT release based on endogenous competition techniques; 4) To develop a radiolabeled agonist to measure high affinity state of 5HT/2A receptors ([123I]/[11C]DOI). Together, these projects should provide new and sophisticated tools for the in vivo characterization of 5-HT neurotransmission in patients with history of suicidal attempts. The radiotracers developed during this funding cycle of the Center will be used in clinical studies in the next funding cycle.