Fibroblast activation protein inhibitor (FAPI) PET imaging in pulmonary fibrosis: pathophysiology, clinical utility, and emerging theranostic applications

Pulmonary fibrosis arises from a dysregulated wound-healing response in which activated fibroblasts drive excessive extracellular matrix deposition and irreversible lung architectural distortion. Conventional high-resolution computed tomography (HRCT) detects largely established structural damage, limiting opportunities for early intervention. The fibroblast activation protein (FAP), a membrane-bound serine protease expressed on activated fibroblasts, presents a potential molecular target for imaging active fibrogenesis. The advent of fibroblast activation protein inhibitor (FAPI)–based radiotracers for positron emission tomography (PET) has been developed to visualize FAP expression in vivo. This review traces the translational continuum from FAP biology through radiotracer development to clinical application of FAPI-PET/CT in interstitial lung diseases, summarising preclinical and emerging human studies investigating FAPI PET/CT in interstitial lung diseases, highlighting preliminary evidence for the detection of early fibroblast activation, potential risk stratification, and monitoring of therapy response. We also discuss the functional heterogeneity of FAP-expressing fibroblast subsets and the interpretive challenges this poses for FAPI imaging. The review also considers early translational work on FAPI-based theranostics, combining diagnostic imaging with fibroblast-targeted radioligand approaches. While FAPI-PET/CT shows promise as a tool for characterizing fibrogenic activity, current evidence remains limited, and prospective studies are needed to clarify its clinical utility and potential role in guiding personalized interventions.