Ga-68-FAPI PET visualize heart failure: from mechanism to clinic

Purpose Heart failure (HF) is a chronic progressive clinical syndrome associated with structural and/or functional heart abnormalities. Active fibroblasts and ventricular remodelling play an essential role in HF progression. Ga-68-labelled fibroblast activation protein (FAP) inhibitor (Ga-68-FAPI) binds to FAP. This study aimed to examine the feasibility of using Ga-68-FAPI positron emission tomography (PET)/computed tomography (CT) to visualize changes in cardiac fibrosis and function over time in the HF setting. Methods After establishing an isoproterenol (ISO)-induced HF rat model (14 consecutive days of intraperitoneal ISO injections), echocardiography and Ga-68-FAPI PET/CT were performed weekly in experimental and control groups. Rat hearts were examined weekly for biodistribution analysis; autoradiography; and haematoxylin and eosin, FAP immunofluorescence and Masson's trichrome staining analysis. Rat blood was sampled weekly for enzyme-linked immunosorbent assay analysis of various plasma indicators. A preliminary clinical study was also performed in seven HF patients who underwent both N-13-amino (NH3) perfusion and Ga-68-FAPI cardiac PET imaging. Results In the animal experiments, myocardial Ga-68-FAPI uptake, expression of FAP and myocardial contractility peaked on day 7 after the initial ISO injection. Only slight fibrotic changes were observed on histopathological examination. Ga-68-FAPI uptake and ventricular wall motion decreased over time as cardiac fibrosis and degree of myocardial injury gradually increased. In the human HF patient study, Ga-68-FAPI PET imaging identified varying degrees of Ga-68-FAPI uptake in the myocardium that did not precisely match with N-13-NH3 myocardial perfusion. Conclusion As HF progresses, Ga-68-FAPI uptake is high in the early stages and then gradually decreases. Although preliminary, our findings suggest that Ga-68-FAPI PET can be used to demonstrate active myocardial fibrosis. Active myocardial FAP expression is followed by myocardial remodelling and fibrosis. Detection of early active FAP expression may assist treatment decision making in HF patients.