(18)F-FAPI PET/CT imaging in pneumoconiosis: a pilot study on a novel tool for early diagnosis and guiding the treatment of pulmonary fibrosis.

BACKGROUND: Pneumoconiosis, characterized by dust-induced pulmonary fibrosis, lacks reliable methods to assess fibrotic activity. This study aimed to monitor fibroblast activation and identify activated pulmonary fibrosis for early diagnosis and anti-fibrotic therapy response by (18)F-fibroblast activation protein inhibitors (FAPI) positron emission tomography/computed tomography (PET/CT) in pneumoconiosis. METHODS: A single-center prospective clinical study was conducted on 6 pneumoconiosis patients and 4 healthy control individuals. The uptake of (18)F-FAPI in the pulmonary fibrosis areas of participants and its correlation with pulmonary diffusion function were analyzed. Sprague-Dawley rat experiments were performed on three groups including pneumoconiosis model, pirfenidone-treated, and normal control groups. (18)F-FAPI and (18)F-fluoro-D-glucose (FDG) PET/CT, histopathologic, and hematological analysis were assessed monthly from modeling until 6 months. RESULTS: In our preliminary cohort, compared to the controls, the (18)F-FAPI uptake in fibrotic areas of pneumoconiosis patients was higher, and a strong negative correlation with the diffusing function was observed (r = -0.929, P = 0.022). In the pneumoconiosis model, (18)F-FAPI activity peaked one month earlier than relative collagen content (%) in Masson trichrome staining and the level of connective tissue growth factor in plasma, an indicator reflecting the fibroblast activation. The uptake of (18)F-FAPI in the pirfenidone-treated group significantly decreased compared to the pneumoconiosis group. Additionally, in pneumoconiosis rats, (18)F-FDG uptake peaked at Month 3, correlating with progressive inflammation (granuloma formation, elevated interleukin-6 [IL-6]/tumor necrosis factor-α [TNF-α]), while pirfenidone showed timepoint-specific metabolic reduction, no significant difference in the overall mean standardized uptake value (SUVmean) was observed. CONCLUSIONS: (18)F-FAPI PET/CT imaging may hold promise for identifying active pulmonary fibrosis and monitoring its progression in pneumoconiosis, suggesting a potential clinical opportunity for targeted anti-fibrotic treatment. These preliminary findings warrant further investigation in larger studies.