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

Tseng W-Y., Chen H-Y., Tsai Y-C., Chan Y-S., Hsieh C-I., Hung S-C., Huang Y-J., Kuo C-F., Yu K-H., Luo S-F., Yu L-S., Lin H-H., Huang Y-S., Williams RO., Wu Y-JJ.

OBJECTIVE: 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. DESIGN: 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. RESULTS: 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). CONCLUSION: 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.

DOI

10.1016/j.biopha.2025.118048

Type

Journal article

Publication Date

2025-06-01T00:00:00+00:00

Volume

187

Keywords

Fibroblast activation protein α, Fibroblast-like synoviocytes, Rheumatoid arthritis, Animals, Arthritis, Rheumatoid, Arthritis, Experimental, Mice, Inbred DBA, Mice, Positron Emission Tomography Computed Tomography, Feasibility Studies, Gallium Radioisotopes, Membrane Proteins, Serine Endopeptidases, Radiopharmaceuticals, Gelatinases, Lutetium, Male, Endopeptidases, Radioisotopes, Fibroblast Activation Protein Alpha

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