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.