Core--Brain imaging

在CCNMD的介绍中回顾的大量证据表明，离散脑区的5-羟色胺(5-HT)神经传递的改变使自杀行为变得脆弱。最近用PET评估体内5-羟色胺神经传递的方法的发展使这一假说在患者身上得到了直接的验证。脑成像核心是一个由来自不同学科(化学、药理学、物理、数学)的科学家组成的综合团队，涵盖开发和支持PET神经受体研究所需的各种专业知识。脑成像核心向该中心提供的服务大致分为四类：1)为该中心的脑成像项目提供后勤支持和技术专长。核心提供研究设计、实施和分析层面的专业知识。此外，这些研究还受益于核心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)为其他核心提供化学和放射化学服务，例如氚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。这些人包括PGF-IV到VI的住院医生，他们正在完成脑成像部门的奖学金，以及该中心的其他研究人员，他们对将脑成像技术应用于情绪障碍和自杀的研究感兴趣。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，我们的开发工作将以PET的5-羟色胺(5-HT)系统为目标。这些目标的选择是以背景部分提供的与自杀易感性有关的神经化学失衡的一般模型为指导的。1)开发和验证使用放射性标记拮抗剂[11C]，DL 100907测量人体5-HT/2A受体结合潜力的方法；2)开发一种新的放射性示踪剂，用正电子发射计算机断层扫描技术([11C]GR127935)测量5-HT/1B受体；3)开发一种新的放射性标记激动剂，以测量5-HT/1A受体([11C]MHA)的激动剂高亲和力状态，并利用该配体和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激动剂，以测量5-HT/2A受体的高亲和力状态([123I]/[11C]DOI)。总之，这些项目应该为有自杀未遂史的患者体内5-羟色胺神经传递的特征提供新的和复杂的工具。在该中心这个供资周期内开发的放射性示踪剂将用于下一个供资周期的临床研究。

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.