18F-FAPI PET/CT Imaging in Pneumoconiosis: a new tool for early diagnosis and guiding treatment of pulmonary fibrosis

Purpose Pneumoconiosis is characterized by pulmonary fibrosis. The activation of fibroblasts play an important role in the pathological development of pulmonary fibrosis. Chest CT, as a conventional examination to diagnose pulmonary fibrosis of pneumoconiosis, cannot evaluate the fibrosis activity. The application value of 18F-FAPI in pneumoconiosis is unclear. This study aimed to clarify the feasibility of 18F-FAPI PET/CT in non-invasively monitoring the activity evolution of pulmonary fibrosis in pneumoconiosis and the anti-fibrotic treatment.

A preliminary clinical study was conducted on 6 pneumoconiosis patients and 4 healthy control individuals, correlation analysis was performed between the 18F-FAPI uptake in pulmonary fibrosis areas and the pulmonary diffusing function. Sprague-Dawley rat experiments were performed on three groups concluding pneumoconiosis model, pirfenidone-treated, and normal control groups. 18F-FAPI and 18F-FDG PET/CT, histopathologic, and hematological analysis were assessed monthly from modeling until 6 months.

18F-FAPI uptake in fibrotic areas was found in the pneumoconiosis patients, and negatively correlated with the diffusing function (r = -0.929, P = 0.022). In the pneumoconiosis model, 18F-FAPI activity preceded 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 18F-FAPI, rather than 18F-FDG, significantly decreased in the pirfenidone-treated group compared to the pneumoconiosis group (P < 0.05).

18F-FAPI PET/CT imaging holds promise for the early identification of pulmonary fibrosis activity and monitoring its evolution in pneumoconiosis, offering a precise clinical opportunity for targeted anti-fibrotic treatment. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study was funded by the National Natural Science Foundation Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Clinical Research Ethics Committee of the First Hospital of Shanxi Medical University I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes Conflicts of interest and sources of funding: none declared. This study is funded by the National Natural Science Foundation (U22A6008) and the Central Guidance for Regional Science and Technology Development Projects (YDZJSX2024B010). Data Availability All data produced in the present study are available upon reasonable request to the authors Abbreviations - CTGF - connective tissue growth factor - DLCO - diffusion lung carbon monoxide - ELISA - enzyme-linked immunosorbent assay - FAP - fibroblast activation protein - FAPI - fibroblast activation protein inhibitors - FVC - forced vital capacity - HRCT - high-resolution computerized tomography - IF - immunofluorescence - IHC - immunohistochemistry - IL-6 - interleukin 6 - PET - Positron Emission Tomography - SUV - standardized uptake value - TBR - target-to-background ratio - TNF-□ - tumor necrosis factor-alpha