Non-invasive imaging of T cells

项目摘要 T细胞是淋巴细胞的一个子集，在免疫应答中发挥重要作用。基于T细胞的疗法 已被用于各种人类疾病，如脑肿瘤，阿尔茨海默病，帕金森病和 多发性硬化T细胞受体（TCR）是参与免疫调节的整合膜蛋白的复合物。 T细胞对抗原的反应。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、增殖来决定细胞命运， 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。用于可视化体内T细胞受体的技术的发展代表了一个关键 了解T细胞在大脑中的正常功能和病理生理学的一步。而且这些 这些技术将加速发现与T细胞受体相互作用的小分子疗法。 该项目旨在开发用于T细胞受体的新型PET成像探针。我们将标记第一个- 类T细胞受体抑制剂，AX-024，与碳-11或氟-18，并评估这些的潜力 通过成像它们的分布，作为人类T细胞受体的放射性示踪剂的分子， 在啮齿动物和非人灵长类动物中的药代动力学。

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.