Work

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

Year: 2025

Type: article

Abstract: 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 68 Ga-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, 177 Lu-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 177 Lu-FAPI-04 reduced arthritis scores by 64 % compared to controls (p < 0.005). Radiotracer 68 Ga-FAPI-04 effectively targets FAPα, enabling PET imaging to identify CIA severity and onset sites in mice. Additionally, 177 Lu-FAPI-04 demonstrated therapeutic potential by mitigating disease activity, suggesting its promise for RA treatment. • Radiolabeled FAPI-04 enables early PET imaging of arthritis onset. • 68 Ga-FAPI-04 uptake correlates with arthritis severity and disease progression. • 177 Lu-FAPI-04 treatment significantly reduces arthritis scores in CIA mice. • FAPα-expressing fibroblasts play a key role in CIA pathogenesis and therapy. • Radiolabeled FAPI-04 shows promise for both CIA diagnosis and targeted therapy.

Source: Biomedicine & Pharmacotherapy

DOI: 10.1016/j.biopha.2025.118048