Non-invasive imaging of T cells

项目摘要 T细胞是淋巴细胞的一个亚群，在免疫反应中发挥着重要作用。基于T细胞的疗法有 被用于各种人类疾病，如脑瘤、阿尔茨海默病、帕金森氏病和 多发性硬化症。T细胞受体(TCR)是一种完整的膜蛋白复合体，参与 T细胞对抗原的反应而激活T细胞。TCR激活促进了许多信号级联反应， 最终通过调节细胞因子的产生、细胞的存活、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 无论是在动物身上还是在人类身上。体内T细胞受体可视化技术的发展是一个关键 了解大脑中T细胞的正常功能和病理生理。此外，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。我们会给第一个打上- T细胞受体抑制剂AX-024与碳-11或氟-18的联合应用 通过成像T细胞受体的分布和分子作为人类T细胞受体的放射性示踪剂 啮齿动物和非人灵长类动物的药代动力学。

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.