Feasibility assessment of radiolabeled FAPI-04 for diagnostic and therapeutic use in rheumatoid arthritis PMID: 40245546

ADC Targets in Oncology

2026-04-10

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].

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.