PET molecular imaging of fibroblast activity after myocardial infarction using a 68Ga-labelled fibroblast activation protein inhibitor (FAPI-04)

Ziel/Aim: Myocardial infarction (MI) and subsequent heart failure (HF) is associated with significant morbidity and mortality worldwide. Spatial and temporal presence of the activated fibroblasts in the injured myocardium predicts the quality of cardiac remodeling post-MI. Therefore, monitoring of activated fibroblasts is of great interest for studying myocardial remodelling after MI. Fibroblast activation protein (FAP) expression is upregulated in activated fibroblasts. This study sought to investigate the potential of a 68 Ga-labelled FAP inhibitor ( 68 Ga-FAPI-04) for PET imaging of activated fibroblasts in a preclinical model of MI. Methodik/Methods: MI and sham-operated rats were scanned with 18 FDG and 68 Ga-FAPI-04, 2 and 6 days post-surgery, respectively. After PET/CT scans animals were euthanized and hearts were harvested for ex vivo imaging using PET/MR. Cryosections were prepared for autoradiography, haematoxylin and eosin (H&E) and immunofluorescence staining. Ergebnisse/Results: In vivo 68 Ga-FAPI-04-PET/CT scans showed elevated regional radioactivity signals in the hypometabolic infarct territory in the myocardium as identified by 18 FDG-PET/CT scans. Tracer uptake in PET scans co-registered well with the infarcted zone confirmed by ex vivo MR scans. In autoradiography images, augmented 68 Ga-FAPI-04 uptake was observed in the infarcts delineated by the H&E staining. Immunofluorescence staining on cardiac cryosections demonstrated the presence of FAP-positive (FAP + ) myofibroblasts. Schlussfolgerungen/Conclusions: 68 Ga-FAPI-04 represents a promising radiotracer for in vivo imaging of post-MI fibroblast activation which may have significant diagnostic and prognostic values, which could aid clinical management of patients after MI.