Noninvasive Monitoring of Early Cardiac Fibrosis in Diabetic Mice by [⁶⁸Ga]Ga-DOTA-FAPI-04 PET/CT Imaging

Cardiac fibrosis represents one of the representative pathological characteristics in the diabetic heart. Active fibroblasts play an essential role in the progression of cardiac fibrosis. The technologies for noninvasive monitoring of activated fibroblasts still have to be investigated. The purpose of this study was to evaluate the feasibility of targeted fibroblast activation protein (FAP) molecular imaging in the early evaluation of diabetic cardiac fibrosis using [⁶⁸Ga]Ga-DOTA-FAPI-04 PET/CT. PET/CT imaging was conducted in db/db mice and db/m mice at weeks 12 and 24. Diabetic heart injury was determined using echocardiography and serum biomarkers. Additionally, the levels of cardiac fibrosis were also assessed. In our study, conventional diagnostic modalities, including echocardiography and serum biomarkers, failed to monitor early-stage cardiac dysfunction and fibrosis in diabetic mice. Conversely, the results of [⁶⁸Ga]Ga-DOTA-FAPI-04 PET/CT imaging demonstrated that diabetic mice had increased myocardial uptake of radioactive tracers in both early-stage and late-stage diabetes, consistent with the elevated FAP expression and increased cardiac fibrosis level. Notably, cardiac PET signals exhibited significant correlations with left ventricular ejection fractions, the E/A ratio, and the level of serum TGF-β1, PIIINP, and sST2. The results demonstrated the potential of [⁶⁸Ga]Ga-DOTA-FAPI-04 PET/CT imaging for visualizing activated fibroblasts and detecting early-stage diabetic heart injury and fibrosis noninvasively. They also demonstrated the clinical superiority of [⁶⁸Ga]Ga-DOTA-FAPI-04 PET/CT imaging over echocardiography and serum biomarkers in the early monitoring of diabetes-related cardiac dysfunction and fibrosis.