Positron emission tomography imaging of T-cell activity in cardiovascular disease and its emerging role in imaging adaptive immunity.

T lymphocytes are central mediators of cardiovascular disease, driving myocardial injury in myocarditis, transplant rejection, post-infarct remodeling, atherosclerosis, and post-viral syndromes. Yet current imaging tools ([18F]FDG PET, somatostatin receptor tracers, CXCR4 PET, and cardiac MRI) offer only indirect or nonspecific measures of immune activity. The ability to noninvasively visualize and quantify T-cell infiltration and activation could transform diagnosis and management in cardio-immunology. Advances in immuno-PET have produced a growing arsenal of T-cell specific tracers. CD8-targeted agents (89Zr-Df-IAB22M2C) and small-molecule probes such as [18F]F-AraG have entered early clinical trials, demonstrating feasibility and safety in humans. Other tracers, including CD4- and CD3-directed antibodies, IL-2R and OX40 probes, checkpoint tracers (PD-1, CTLA-4), and granzyme B ligands, remain largely preclinical but show strong potential for cardiovascular translation. Applications span acute myocarditis, noninvasive transplant rejection surveillance, assessment of post-MI immune remodeling, plaque vulnerability in atherosclerosis, and systemic immune activation in long COVID. Compared with existing imaging modalities, T-cell PET offers cell-type specificity, quantitative longitudinal monitoring, and the capacity for whole-body immune mapping, particularly when integrated with total-body PET or hybrid PET/MR. Challenges include low T-cell density in the myocardium, tracer specificity, radiation burden, and the need for histopathologic validation. Future directions involve repurposing oncology tracers for cardiology, engineering antibody fragments with improved kinetics, and establishing T-cell PET as a mechanistic biomarker in cardiovascular clinical trials. With further innovation and validation, T-cell PET has the potential to evolve from an experimental tool into a clinically actionable modality, reshaping the management of immune-mediated heart disease.