Abstract Introduction Progressive fibrosing interstitial lung diseases (ILD) and idiopathic pulmonary fibrosis (IPF) are associated with a poor prognosis. To date, there is no imaging method that can reliably detect fibrotic disease activity. We have previously reported on the significance of positron emission tomography/computed tomography (PET/CT) with fibroblast activation protein inhibitor (FAPi). The aim of this study was to investigate the feasibility and potential diagnostic value of 68GaGa-FAPi-46 PET/CT at two time points in patients with IPF and progressive pulmonary fibrosis (PPF), including hypersensitivity pneumonitis (PPF-HP) and connective tissue disease-associated ILD (PPF-CTD-ILD). Methods This prospective, single-center study included 29 consecutive IPF and ILD patients who were not receiving antifibrotic treatment. All patients underwent 68GaGa-FAPi-46 PET/CT imaging 10 and 60 minutes after injection. In addition, 25 of these patients underwent bronchoscopy with transbronchial biopsy and analysis of FAP protein expression by immunohistochemistry (IHC). Early and late pulmonary FAPi uptake was compared between patients with IPF and PPF-HP or PPF-CTD-ILD and correlated with PFT and FAP expression by IHC in lung tissue. Results In general, we observed significant inverse correlations between TLC and TL-FAPi after 10 minutes (r = -0.402, p = 0.030) and 60 minutes (r = -0.447, p = 0.015), as well as between FAV after 10 minutes and DLCO (r = -0.415, p = 0.049). In IPF patients, strong negative correlations were observed between DLCO and TL-FAPi (r = -0.884, p = 0.047) and between DLCO and FAV after 10 minutes (r = -0.893, p = 0.041). Significant correlations between lung function-measurable disease progression and the 68GaGa-FAPi-46 PET/CT activity indicator were also observed in the PPF-ILD subgroups. In each case, this was more accurate than a concomitant analysis from the invasively obtained lung biopsies. Conclusion 68GaGa-FAPi-46 PET/CT enables highly sensitive in vivo detection of fibroblast activity in IPF and ILD and shows disease-specific uptake patterns. The 68GaGa-FAPi PET parameters correlate better with lung function impairment than immunohistological FAP expression analysis, which is due to the often pleural-adjacent nature of the disease and the associated sampling error of transbronchial biopsy. This underscores the potential of 68GaGa-FAPi-46 PET/CT as a diagnostic tool for determining active fibrosis. Imaging at two time points confirmed that high-contrast imaging can be achieved as early as 10 minutes after injection and that 68GaGa-FAPi-46 can support early diagnosis and personalized antifibrotic treatment planning in IPF and PPF-ILD. This abstract is funded by: n/a
Gagiannis et al. (Fri,) studied this question.