Assessment of active fibrotic remodeling in patients with idiopathic pulmonary fibrosis (IPF)/progressive pulmonary fibrosis (PPF) using dual-time-point [⁶⁸Ga]Ga-FAPI-46-PET/CT.

Abstract

BackgroundProgressive fibrosing interstitial lung diseases (ILD) continue to have a poor prognosis. To date, there is no imaging method that can reliably detect fibrotic remodeling processes or distinguish between active and dormant fibrotic changes in the lungs. The novel PET/CT with fibroblast activation protein inhibitor (FAPI) targets activated fibroblasts. The aim of this study was to evaluate the feasibility of [⁶⁸Ga]Ga-FAPI-46 PET/CT to detect and quantify fibroblast-related pulmonary activity, and to explore the association between this activity and pulmonary function, as well as the histopathological expression of FAP across patients with IPF and progressive pulmonary fibrosis (PPF) subtypes.MethodsThis prospective, observational, single-center study included 29 consecutive IPF and ILD patients without antifibrotic treatment. All patients underwent routine clinically indicated [⁶⁸Ga]Ga-FAPI-46 PET/CT imaging. Early and late FAPI uptake in the lungs was compared between patients with IPF, PPF-HP, and PPF-CTD-ILD, as well as with FAP expression in lung tissue.ResultsFibrotic areas across IPF and ILD subtypes showed increased FAPI uptake with higher SUVmax (p = 0.037) and lesion-to-background ratios (LBR) values (p = 0.016) after 10 minutes in non-IPF patients compared to IPF patients (SUVmax 6.65, IQR 5.66-7.82 vs. SUVmax 5.24, IQR 4.54-6.49). In general, we observed significant inverse correlations between TLC and lung total lesion FAPI (TL-FAPI) at 10 minutes (r = -0.402, p = 0.030) and 60 minutes (r = -0.447, p = 0.015), as well as between lung FAPI metabolic active volume (FAV) after 10 minutes and DLCO (r = -0.415, p = 0.049). Significant correlations were also found in the subgroups of the various ILDs. FAP score was significantly higher in IPF patients (p = 0.014); however, no significant correlation was observed between FAP score and PET-derived parameters."ConclusionFAPI-PET/CT could enable sensitive in vivo detection of fibroblast activity in IPF and ILD and may show disease-specific uptake patterns. FAPI-PET parameters correlate with pulmonary function impairment, underscoring their potential as biomarkers for active fibrosis.