Core--Brain imaging

核心--脑成像

• 批准号: 6643689
• 负责人: MARC A LARUELLE
• 金额: $ 17.72万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6643689
• 关键词: baboons; bioimaging /biomedical imaging; biomedical facility; brain imaging /visualization /scanning; clinical research; human subject; laboratory mouse; laboratory rat; positron emission tomography; radiotracer; serotonin; serotonin receptor

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.

在引入该CCNMD的引入中回顾的许多证据表明，在离散的大脑区域中5-羟色胺（5-HT）神经传递的改变赋予了自杀行为的脆弱性。使用PET评估体内5-HT神经传递的方法的最新发展允许直接检验患者的假设。大脑成像核心是来自各个学科（化学，药理学，物理，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范围。大脑成像核心提供给中心的服务分为四个一般类别：1）为中心的大脑成像项目提供后勤支持和技术专业知识。核心在研究设计，实施和分析的水平上提供了专业知识。此外，这些研究受益于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）向其他核心提供化学和放射化学服务，例如tri骨配体或其他商业上无法获得的化合物。 3）向年轻研究人员提供脑成像的培训。其中包括对正在完成大脑成像部门研究金的研究金的PGF-IV，以及中心的其他研究人员，对将脑成像技术应用于情绪障碍和自杀的研究感兴趣。 4）开发与自杀研究有关的新成像方式。在接下来的五年中，我们的开发工作将针对使用PET的5-羟色胺（5-HT）系统。这些目标的选择是由与背景部分中提供的自杀脆弱性相关的神经化学失衡的一般模型指导。 1）使用放射性标记的拮抗剂[11C]，DL 100907开发和验证人类中5HT/2A受体结合电位的度量； 2）开发新的放射性示例以用PET测量5-HT/1B受体（[11C] GR127935）； 3）开发一种新的放射标记的激动剂，以测量5-HT/1A受体（[11C] MHA）的激动剂高亲和力状态，并使用该配体开发基于内源性竞争技术的5-HT释放的度量； 4）开发一个放射标记的激动剂，以测量5HT/2A受体的高亲和力状态（[[123i]/[11c] doi）。这些项目共同为有自杀尝试史的患者提供了5-HT神经传递的体内表征的新工具。在下一个融资周期中，将在该中心的融资周期中开发的放射性示例。