Targeting Fibroblast Activation Protein for Molecular Imaging of Fibrotic Remodeling in Pulmonary Arterial Hypertension.

The purpose of this study was to investigate the feasibility of using F-labeled fibroblast activation protein inhibitor (FAPI) PET/CT in assessing the fibrotic remodeling of the pulmonary artery (PA) and the right ventricle (RV) in pulmonary arterial hypertension (PAH). In a rat model of monocrotaline-induced PAH, rats were euthanized at different time points for tissue analysis (fibroblast activation protein immunofluorescence and Masson's trichrome staining) after completing F-FAPI PET/CT and hemodynamic measurements. Thirty-eight PAH patients were enrolled to participate in F-FAPI PET/CT imaging, with right heart catheterization and echocardiography performed within 1 wk to assess pulmonary hemodynamics and cardiac function. In the animal experiments, RV systolic pressure in monocrotaline rats increased from day 14 to day 21 after injection. F-FAPI uptake and fibroblast activation protein expression in the myocardium and lungs peaked on day 14 after injection. Collagen deposition in the RVs and peripheral PAs of monocrotaline rats progressively deteriorated from day 14 to day 21. In the human PAH study, F-FAPI PET/CT imaging identified varying degrees of F-FAPI uptake in the myocardium and proximal and distal PAs, correlating with clinical, RV function, and pulmonary hemodynamic parameters. Among the 5 follow-up patients who underwent a second F-FAPI PET/CT scan after 6 mo (range, 4-9 mo) of PAH-targeted therapy, 3 demonstrated reduced F-FAPI uptake, corresponding with clinical improvement. F-FAPI PET/CT imaging is feasible for visualizing the remodeling of the PA and the RV in PAH. Although it offers promise for assessing disease-related changes, its role in evaluating disease severity and monitoring therapeutic efficacy requires further investigation.