Monitoring activation and trafficking of immune cells throughout the body using molecular imaging will significantly impact the diagnosis and treatment evaluation of immune disorders. In contrast to numerous applications of positron emission tomography (PET) in cancer and other diseases, relatively few studies have used this molecular imaging modality to visualize immune responses. Our group aims to develop new PET imaging approaches to visualize T cell trafficking and function in vivo in animal models of autoimmunity and cancer immunotherapy.

The objectives of the current proposal are twofold. First, we will investigate whether PET reporter gene imaging could enable visualization of T cell trafficking to the central nervous system in Experimental Autoimmune Encephalomyelitis (EAE). These studies will use the human thymidine kinase 2 (ΔhTK2), a novel PET reporter gene. Second, we propose to develop PET approaches to enable direct measurements of immune function in vivo, without the addition of a reporter gene.

We have recently demonstrated that ¹⁸fluorodeoxyglucose ([¹⁸F]FDG) can be used to monitor the onset of EAE and responses to immunosuppressive therapy (Radu et al. PNAS, 2007). To identify new probes specific for biochemical pathways upregulated in activated T cells, we have directed our attention to the nucleoside metabolism. We hypothesize that changes in the deoxyribonucleoside salvage pathway during T cell activation could be detected by microPET using ¹⁸F-labeled nucleoside analogs. Recent preliminary data support this hypothesis. Using a differential screening approach, we identified a novel ¹⁸F-labeled 2’-deoxycytidine analog that enables visualization of lymphoid organs and localized immune activation in animal models.

Successful completion of proposed studies should widen the utility of PET imaging of immune status in the preclinical and clinical settings and could shed new light on the complex spatiotemporal programming of adaptive immune responses against self antigens.