FAPI PET Reveals Active Fibroblast-Driven Remodeling Beyond Infarct Scar

BACKGROUND Post-myocardial infarction (MI) remodeling is driven by dynamic interactions between inflammatory and fibrotic processes. Conventional imaging techniques primarily detect established scar but fail to capture active fibroblast-mediated remodeling. OBJECTIVES We aimed to determine whether [68Ga]Ga-FAPI-46 PET/CT can identify biologically active myocardial remodeling beyond established infarct scar using a multi-tracer molecular imaging approach in patients with early post-MI (≤1 month after MI) and late post-MI (>1 month after MI). METHODS In this prospective study, 31 patients with early post-MI (≤1 month after MI) (n = 10) or late post-MI (>1 month after MI) (n = 21) and 10 control subjects underwent [68Ga]Ga-FAPI-46 PET/CT, [18F]FDG PET/CT, and myocardial perfusion imaging using [99mTc]Tc-MIBI SPECT. FAPI uptake was quantified using SUVmax, SUVmean, fibroblast activation volume (FAV), and total lesion FAPI (TLF). FAPI uptake patterns were characterized according to their spatial relationship with FDG metabolism, distinguishing infarct-associated and mixed phenotypes. RESULTS Myocardial FAPI uptake was observed in 87% of patients with MI and was significantly higher than in controls (SUVmax: 4.21 vs. 2.64, p = 0.01; SUVmean: 2.46 vs. 1.35, p = 0.001). In our cohort, two patient-level phenotypes were observed: a reparative pattern restricted to metabolically inactive infarct regions (48%) and a mixed pattern showing FAPI uptake in both infarct regions and FDG-preserved myocardium (52%). No patients exhibited a purely FDG-preserved FAPI-positive pattern. No significant differences in quantitative FAPI parameters were observed between early and late post-MI. Notably, in a subset of patients, myocardial FAPI uptake extended beyond metabolically inactive infarct regions into adjacent FDG-preserved myocardium, suggesting spatially heterogeneous fibroblast-associated remodeling. Stratification based on median TLF demonstrated that higher FAPI burden was more frequently associated with mixed fibrosis patterns. Multi-tracer imaging enabled identification of hibernating myocardium in a subset of patients. CONCLUSIONS [68Ga]Ga-FAPI-46 PET/CT enables noninvasive visualization of active fibroblast-associated myocardial remodeling following MI. Integrated assessment with [18F]FDG PET demonstrated spatially heterogeneous FAPI uptake involving metabolically inactive infarct regions and, in a subset of patients, adjacent FDG-preserved myocardium. The complementary information provided by these radiotracers may improve biological characterization of post-infarction myocardial remodeling, although the significance of FAPI uptake within FDG-preserved myocardium requires further investigation.