Expanding horizons: radiolabeled FAPI in imaging of autoimmune diseases

Fibroblast activation protein alpha (FAP) is a type II transmembrane protease that exhibits both dipeptidyl peptidase and endopeptidase activities. It is upregulated in activated fibroblasts, particularly in tumor stroma and in fibrotic processes associated with various benign conditions. Recent studies have revealed that FAP is also highly expressed in certain Autoimmune Diseases (AIDs) characterized by chronic inflammation and tissue remodeling. Small-molecule inhibitors targeting FAP (FAPI) positron emission tomography (PET) provides a direct imaging modality for assessing fibroblast activation in vivo. FAPI's application in oncology has attracted considerable attention in nuclear medicine. However, evidence supporting its efficacy in AIDs remains limited. This review systematically evaluates the diagnostic and phenotyping potential of FAPI PET in AIDs, expands its applications across a broader disease spectrum, highlights technical advantages, and delineates future research directions.