Mitochondrial Imaging Detects Early Cardiac Changes Following Cancer Immunotherapy

Purpose: Advances in cancer therapy have improved survival but increased the risk of treatment-related cardiotoxicity, which remains difficult to detect early with existing biomarkers. [¹⁸F]F-AraG is a PET tracer that targets cells with active mitochondrial biogenesis, including cardiomyocytes and activated T cells, and may enable concurrent assessment of cardiac involvement and therapy-associated immune activity. This study evaluated whether [¹⁸F]F-AraG PET can serve as an early imaging biomarker of cardiac effects across different cancer therapies. Methods: Twenty-six healthy subjects underwent [¹⁸F]F-AraG PET to establish baseline myocardial uptake. Seven patients with stage III melanoma and ten with advanced non-small cell lung cancer were imaged before and after immunotherapy. Myocardial uptake (SUVmax, SUVmean, SUVtotal) was quantified in the left (LV) and right (RV) ventricles, with LV regional uptake analyzed using a 17-segment model. Myocardial uptake was examined in relation to abnormal cardiac status in a subset of patients with available electrocardiogram (ECG) data. Associations between cardiac uptake, mitochondrial content, and PGC-1α expression were evaluated. Results: Healthy myocardium demonstrated consistent and spatially uniform [¹⁸F]F-AraG uptake across age and sex, with higher uptake in the LV than RV. Conventional therapy was associated with increased global myocardial uptake, whereas immunotherapy was associated with additional heterogeneous and focal myocardial uptake. Altered myocardial uptake patterns were observed in patients with ECG abnormalities. Conclusions: [¹⁸F]F-AraG PET detects therapy-associated changes in myocardial tracer uptake following cancer treatment. These findings support its potential utility as a noninvasive imaging approach for early evaluation of cardiac effects in patients receiving cancer therapies.