Functional MRI for Brain Imaging: Design and synthesis of DOTA-based Gd contrast agents for tracking neurotransmitter

用于脑成像的功能性 MRI：设计和合成基于 DOTA 的 Gd 造影剂，用于跟踪神经递质

• 批准号: 320225462
• 负责人: Dr. Jessica Wahsner
• 金额: --
• 依托单位: Athinoula A. Martinos Center for Biomedical Imaging
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/320225462?language=en
• 关键词: Functional; MRI; Brain; Imaging; Design

The overall goal of this project is to develop novel molecular magnetic resonance probes for neuroimaging applications. Such sensors can be employed in selective neurotransmitter imaging approaches in the living brain (in this project: glutamate and gamma-aminobutyric acid (GABA)) by using non-invasive functional magnetic resonance imaging (fMRI). The aim of this technique is to obtain new insights into the mechanisms of neural functions and, moreover, it could be crucial for the diagnosis and therapy of brain disorders. To meet this goal, in a collaboration between Peter Caravan (Massachusetts General Hospital/Harvard Medical School) and Alan Jasanoff (Massachusetts Institute of Technology), we will conjugate molecular MRI contrast agents to appropriate protein domains. The gadolinium based contrast agent provides the requested MR signal, while the corresponding biomolecule selectively binds specific neurotransmitters. Hence, the combination of these properties within one bioconjugate forms the basis for a new family of MRI sensors. Appropriate MRI contrast agents that are required for the preparation of such bioconjugates can be generated in great diversity employing the modular synthetic strategies. The properties of the resulting sensors will be characterized using magnetic resonance measurements to identify neurotransmitter sensitive probes suitable for fMRI applications.

该项目的总体目标是开发用于神经成像应用的新型分子磁共振探针。这种传感器可以通过非侵入性功能磁共振成像（fMRI）用于活体大脑的选择性神经递质成像方法（在这个项目中：谷氨酸和γ -氨基丁酸（GABA））。这项技术的目的是获得神经功能机制的新见解，此外，它可能对脑部疾病的诊断和治疗至关重要。为了实现这一目标，在Peter Caravan（麻省总医院/哈佛医学院）和Alan Jasanoff（麻省理工学院）的合作下，我们将把分子MRI对比剂偶联到合适的蛋白质结构域上。钆基造影剂提供所需的MR信号，而相应的生物分子选择性地结合特定的神经递质。因此，在一个生物偶联物中结合这些特性形成了一个新的MRI传感器家族的基础。制备这种生物偶联物所需的适当MRI造影剂可以采用模块化合成策略以多种方式生成。由此产生的传感器的特性将使用磁共振测量来识别适合于功能磁共振成像应用的神经递质敏感探针。