Core--Brain imaging

在本CCNMD的介绍中回顾了许多证据，表明血清素（5-HT）神经传递在离散脑区域的改变导致了自杀行为的易感性。用PET评估体内5-HT神经传递的最新发展方法允许在患者中直接测试这一假设。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。脑成像核心为中心提供的服务大致分为四类：1)为中心脑成像项目提供后勤支持和技术专长。核心部分提供研究设计、实施和分析层面的专业知识。此外，这些研究受益于由核心维护的一般基础设施，例如放射化学实验室和图像分析工作站。2)为其他核心提供化学和放射化学服务，例如氚化配体或其他商业上无法获得的化合物。3)为年轻研究者提供脑成像方面的培训。其中包括PGF-IV至VI住院医生，他们正在脑成像部门完成奖学金，以及中心其他对应用脑成像技术研究情绪障碍和自杀感兴趣的研究人员。4)开发与自杀研究相关的新成像模式。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提供的与自杀脆弱性相关的神经化学失衡的一般模型指导的。1)利用放射性标记拮抗剂开发并验证5HT/2A受体在人体内的结合潜力[11C]，DL 100907；2)利用PET （[11C]GR127935）研制新的5-HT/1B受体示踪剂；3)开发一种新的放射标记激动剂来测量5-HT/1A受体（[11C]MHA）的高亲和力状态，并利用该配体开发一种基于内源性竞争技术的5-HT释放测量方法；4)开发一种放射性标记的激动剂来测量5HT/2A受体的高亲和力状态（[123I]/[11C]DOI）。总之，这些项目应该提供新的和复杂的工具，在体内表征5-HT神经传递的患者有自杀企图。本中心本次资助周期开发的放射性示踪剂将在下一个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.