Non-invasive imaging of T cells

T 细胞的非侵入性成像

基本信息

批准号：
10015276
负责人：
Changning Wang
金额：
$ 8.3万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-10 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10015276
关键词：
Actins Adaptor Signaling Protein Alzheimer&apos s Disease Animals Antigens Asthma Autoimmune Process Binding Biological Assay Body Weight decreased Brain Brain Neoplasms Brain imaging C-terminal Carbon Cell Survival Cell physiology Cells Cladribine Complex Cytoskeleton Data Development Disease Dose Drug Kinetics Experimental Autoimmune Encephalomyelitis FDA approved Fluorine Functional disorder Genes Goals Histone Deacetylase Human Image Imaging Device Imaging Techniques Immune response Immunization Immunomodulators Immunosuppressive Agents Impairment Inflammatory Integral Membrane Protein Investigative Techniques Knockout Mice Label Lymphocyte Subset Magnetic Resonance Imaging Mature T-Lymphocyte Mediating Medical Research Metabolism Methods Modeling Molecular Probes Molecular Weight Multiple Sclerosis Mus N-terminal Neurologic Neurologic Symptoms Oral Parkinson Disease Pharmaceutical Preparations Pharmacology Pharmacotherapy Plasma Play Positioning Attribute Positron-Emission Tomography Process Production Proline Psoriasis Radiolabeled Receptor Activation Receptor Signaling Regulation Reporting Research Resources Rodent Role Signal Pathway Signal Transduction T cell therapy T-Cell Activation T-Cell Receptor T-Lymphocyte Techniques Therapeutic Effect Tissues Translating axon guidance bioimaging cell motility copolymer 1 cytokine design drug discovery experience first-in-human human disease human imaging imaging probe in vivo in vivo imaging inhibitor/antagonist kinetic model man molecular imaging multiple sclerosis treatment non-invasive imaging nonhuman primate novel prevent radiochemical radiotracer receptor receptor density recruit response small molecule therapeutics src Homology Region 2 Domain technique development tool treatment response

项目摘要

Project Summary T-cells are a subset of lymphocytes that play a large role in the immune response. T cell based therapies have been used in various human diseases, such brain tumors, Alzheimer’s disease, Parkinson’s disease and Multiple sclerosis. The T-cell receptor (TCR) is a complex of integral membrane proteins that participate in the activation of T-cells in response to an antigen. TCR activation promotes a number of signaling cascades that ultimately determine cell fate through regulating cytokine production, cell survival, proliferation, and differentiation Unfortunately, there are no suitable non-invasive imaging tools for investigating these processes in animals or in man. The development of techniques for visualizing T cell receptors in vivo represents a key step in understanding both the normal function and pathophysiology of T cells in brain. Moreover, these techniques will accelerate the discovery of small molecule therapeutics that interacts with the T cell receptors. The project is designed to develop novel PET imaging probes for T cell receptors. We will label the first-in- class T cell receptor inhibitor, AX-024, with carbon-11 or fluorine-18 and evaluate the potential of these molecules to serve as radiotracers for T cell receptors in humans by imaging their distribution and pharmacokinetics in rodents and non-human primates.

项目摘要 T细胞是在免疫响应中起着重要作用的淋巴细胞的子集。基于T细胞的疗法具有用于各种人类疾病，此类脑肿瘤，阿尔茨海默氏病，帕金森氏病和多发性硬化症。 T细胞受体（TCR）是参与参与的整体膜蛋白的复合体响应抗原的T细胞激活。 TCR激活促进了许多信号级联最终通过调节细胞因子的产生，细胞存活，增殖和不幸的是，没有合适的非侵入性成像工具来研究这些过程在动物或人类中。在体内可视化T细胞受体的技术的开发代表了关键了解大脑中T细胞的正常功能和病理生理学。而且，这些技术将加速与T细胞接收器相互作用的小分子疗法的发现。该项目旨在为T细胞接收器开发新颖的PET成像问题。我们将标记第一个 T类细胞受体抑制剂AX-024，含碳-11或氟-18，并评估这些潜力通过成像分布和啮齿动物和非人类隐私的药代动力学。