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

Abstract PurposeHeart failure (HF) is a chronic and progressive clinical syndrome with structure or functional abnormalities of the heart. Active fibroblasts and ventricular remodeling play an essential role in the progression of HF. 68Ga-labeled fibroblast activating protein inhibitor (68Ga-FAPI) have been proved binding with fibroblast activation protein (FAP) in many diseases. This study aimed to use 68Ga-FAPI PET to continuously visualize the dynamic change process of cardiac fibroblasts and HF to aid in the clinical management of HF.MethodsThe rat model of HF was established by injection of isoproterenol for 14 d continuously. Echocardiography and 68Ga-FAPI were performed weekly. Isolated hearts were taken every week for biodistribution, autoradiography, hematoxylin-eosin, FAP-immunofluorescence and Masson's trichrome staining, and blood samples for enzyme‑linked immunosorbent assay. A preliminary study of HF patients further recruited for 13N-amino (13N-NH3) perfusion and 68Ga-FAPI cardiac PET imaging simultaneously.ResultsExtensive myocardial uptake of 68Ga-FAPI, expression of FAP, and myocardial contractility peaked at 7 d after the onset of modeling, while only slight fibrotic changes were manifested. With time extension, 68Ga-FAPI uptake and ventricular wall motion of the heart reduced, while cardiac fibrosis and degree of myocardial injury gradually increased. Seven patients diagnosed with HF were successfully enrolled (5 men and 2 women, 58.14 ± 16.25 years). 13N-NH3 perfusion was inconsistent with 68Ga-FAPI uptake. Higher myocardial 68Ga-FAPI uptake was demonstrated in the patients with < 1-year duration than other groups. ConclusionWith the progress of HF, 68Ga-FAPI accumulates evidently in the early stage, and gradually reduced. Preliminary clinical study suggested that 68Ga-FAPI PET could be used to display active fibrosis. Active myocardial FAP expression is followed by myocardial remodeling and myocardial fibrosis, suggesting that the detection of early active FAP expression may help guiding antifibrotic-drug therapy. Clinical Trial RegistrationNCT04982458