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

  • Biomed Pharmacother. 2025 Jun:187:118048. doi: 10.1016/j.biopha.2025.118048.
Wen-Yi Tseng  1 ,  Hong-Yi Chen  2 ,  Yun-Chen Tsai  3 ,  Yi-Sheng Chan  4 ,  Chen-I Hsieh  5 ,  Shih-Che Hung  6 ,  Yun-Ju Huang  7 ,  Chang-Fu Kuo  8 ,  Kuang-Hui Yu  9 ,  Shue-Fen Luo  10 ,  Ling-Shan Yu  11 ,  Hsi-Hsien Lin  12 ,  Yi-Shu Huang  13 ,  Richard O Williams  14 ,  Yeong-Jian Jan Wu  15
Affiliations
  • 1. School of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Keelung, Keelung 20401, Taiwan. Electronic address: [email protected].
  • 2. School of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. Electronic address: [email protected].
  • 3. Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan. Electronic address: [email protected].
  • 4. School of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Department of Orthopedic Surgery, Chang-Gung Memorial Hospital, Keelung, Keelung 20401, Taiwan. Electronic address: [email protected].
  • 5. Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan. Electronic address: [email protected].
  • 6. School of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. Electronic address: [email protected].
  • 7. School of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan. Electronic address: [email protected].
  • 8. School of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan. Electronic address: [email protected].
  • 9. Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan. Electronic address: [email protected].
  • 10. Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan. Electronic address: [email protected].
  • 11. Institute of BioPharmaceutical Sciences, College of Medicine, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. Electronic address: [email protected].
  • 12. Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. Electronic address: [email protected].
  • 13. Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Keelung, Keelung 20401, Taiwan; Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, United Kingdom. Electronic address: [email protected].
  • 14. Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, United Kingdom. Electronic address: [email protected].
  • 15. School of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Keelung, Keelung 20401, Taiwan. Electronic address: [email protected].
PMID: 40245546 DOI: 10.1016/j.biopha.2025.118048
Abstract

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.

Keywords
Fibroblast activation protein α; Fibroblast-like synoviocytes; Rheumatoid arthritis.
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-128643
    FAPI-4
    99.47%, FAP Inhibitor
    target: FAP
    Research Areas: Cancer