Feasibility assessment of radiolabeled FAPI-04 for diagnostic and therapeutic use in rheumatoid arthritis

Fibroblast activation protein alpha (FAPα) plays a key role in cartilage degradation, inflammation, and bone erosion, particularly in rheumatoid arthritis (RA) where fibroblast-like synoviocytes in synovial tissue show elevated FAPα expression. This study explored radiolabeled FAP inhibitors for arthritis diagnosis and therapy.

We used the radiotracer ⁶⁸Ga-FAPI-04 for PET/CT imaging to predict collagen-induced arthritis (CIA) onset. Weekly scans quantified tracer uptake via SUV values, correlating results with disease scores and incidence. For therapeutic evaluation, ¹⁷⁷Lu-FAPI-04 targeted FAPα-expressing cells, and arthritis scores of treated CIA mice were compared with untreated controls using one-way ANOVA.

CIA mice with elevated SUV one week post-booster immunization had a 94.6 % arthritis incidence. SUV correlated with arthritis severity, reflecting increased FAPα expression. Treatment with ¹⁷⁷Lu-FAPI-04 reduced arthritis scores by 64 % compared to controls (p < 0.005).

Radiotracer ⁶⁸Ga-FAPI-04 effectively targets FAPα, enabling PET imaging to identify CIA severity and onset sites in mice. Additionally, ¹⁷⁷Lu-FAPI-04 demonstrated therapeutic potential by mitigating disease activity, suggesting its promise for RA treatment.