Fibroblast activation protein-targeted molecular imaging in interstitial lung disease: a systematic review

Interstitial lung diseases (ILDs) are characterized by progressive lung scarring. Fibroblast activation protein (FAP), overexpressed on activated fibroblasts, has emerged as a key molecular target for imaging active fibrosis. This systematic review synthesizes the current evidence on the role of FAP-targeted imaging in evaluating ILD. A systematic search was conducted across PubMed, Scopus, and Web of Science according to PRISMA guidelines. Twelve studies met the inclusion criteria and were included in a qualitative synthesis. FAP inhibitors (FAPI) imaging consistently demonstrated elevated tracer uptake in ILD patients, showing strong spatial correlation with fibrotic patterns on high-resolution computed tomography (HRCT), particularly reticulation. Increased FAPI uptake was significantly associated with declining lung function, including forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO). Histopathological analyses confirmed that FAPI uptake corresponds to fibroblast-rich regions, validating its specificity for active fibrogenesis. Dual-tracer imaging showed potential in differentiating fibrotic from inflammatory activity. FAP-targeted imaging is a promising non-invasive modality for visualizing and quantifying active fibrosis in ILD. It offers valuable insights into disease activity, functional impairment, and prognosis, potentially guiding personalized treatment strategies.