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

Abstract

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. ⁶⁸Ga-labelled fibroblast activation protein (FAP) inhibitor (⁶⁸Ga-FAPI) binds to FAP. This study aimed to examine the feasibility of using ⁶⁸Ga-FAPI positron emission tomography (PET)/computed tomography (CT) to visualize changes in cardiac fibrosis and function over time in the HF setting. After establishing an isoproterenol (ISO)-induced HF rat model (14 consecutive days of intraperitoneal ISO injections), echocardiography and ⁶⁸Ga-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 ¹³N-amino (NH₃) perfusion and ⁶⁸Ga-FAPI cardiac PET imaging. In the animal experiments, myocardial ⁶⁸Ga-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. ⁶⁸Ga-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, ⁶⁸Ga-FAPI PET imaging identified varying degrees of ⁶⁸Ga-FAPI uptake in the myocardium that did not precisely match with ¹³N-NH₃ myocardial perfusion. As HF progresses, ⁶⁸Ga-FAPI uptake is high in the early stages and then gradually decreases. Although preliminary, our findings suggest that ⁶⁸Ga-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. NCT04982458.