Evaluation of ¹⁸F-FAPI-04 Imaging in Assessing the Therapeutic Response of Rheumatoid Arthritis

PurposeFibroblast activating protein (FAP) is highly expressed in the synovial tissues of rheumatoid arthritis (RA) patients. The aim of this study was to determine the feasibility of PET imaging with an Al[F-18] F-NOTA-labeled FAP inhibitor 04(F-18-FAPI-04) for the evaluation of arthritic progression and therapeutic response in experimental arthritis.MethodsFibroblast-like synoviocytes (FLSs) were obtained from patients with RA or osteoarthritis (OA), and the relationship between F-18-FAPI-04 uptake and the inflammatory activity of RA FLSs was investigated. Collagen-induce arthritis (CIA) mice models were established and treated with methotrexate (MTX) or etanercept (ETC). Then, PET imaging was performed 24 h following F-18-FAPI-04 injection. The imaging results were compared by assessing macroscopic arthritis scores and histological staining.Results(18)F-FAPI-04 uptake was obvious in RA FLSs that characterizing FAP activation. The higher the uptake of F-18-FAPI-04, the more severity of the inflammatory phenotype in RA FLS. Furthermore, the uptake of F-18-FAPI-04 in inflamed joints could be found even before the deformity of the parental joints could be observed by histological examination. Both MTX and ETC were effective in inhibiting the progression of arthritis in CIA mice was confirmed by macroscopic, histological, and radiographic pathology scores. Importantly, F-18-FAPI-04 uptake declined accordingly in CIA models following MTX and ETC treatment.ConclusionsThese findings suggest that PET imaging of F-18-FAPI-04 can be used to monitor treatment response in RA, and is more sensitive in disease speculation than macroscopic arthritis scoring.