Abstract
Advances in cancer therapy have improved survival but introduced substantial cardiac risk. Mitochondrial dysfunction underlies cardiotoxicity from conventional therapy, while T cell infiltration drives immunotherapy-related myocarditis. Early detection remains challenging, as current biomarkers and imaging lack sensitivity. Here, we show that [ (18) F]F-AraG, a mitochondrial PET tracer that images both activated T cells and cardiomyocytes, may provide an early biomarker of cardiac involvement across different cancer therapies. Healthy cardiac uptake was clearly detectable, consistent across age and sex, and spatially uniform. In patients with cancer, conventional therapy increased cardiac uptake, while immune checkpoint inhibitors induced further increases and regional heterogeneity suggestive of T cell infiltration. Abnormal [ (18) F]F-AraG cardiac uptake patterns were observed alongside ECG abnormalities. These findings establish [ (18) F]F-AraG PET as a first-in-class imaging tool for simultaneous assessment of early anti-tumor immunity and cancer therapy-related cardiac effects.