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: skipwenyi@cgmh.org.tw.
2 School of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. Electronic address: D000017406@cgu.edu.tw.
3 Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan. Electronic address: b9502085@cgmh.org.tw.
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: yschan512@gmail.com.
5 Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan. Electronic address: jennifershie@gmail.com.
6 School of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. Electronic address: zack102353113@gmail.com.
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: b9502071@cgmh.org.tw.
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: zandis@adm.cgmh.org.tw.
9 Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan. Electronic address: gout@adm.cgmh.org.tw.
10 Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan. Electronic address: lsf00076@adm.cgmh.org.tw.
11 Institute of BioPharmaceutical Sciences, College of Medicine, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. Electronic address: lingshanyu@mail.nsysu.edu.tw.
12 Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. Electronic address: hhlin@mail.cgu.edu.tw.
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: i-shu.huang@kennedy.ox.ac.uk.
14 Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, United Kingdom. Electronic address: richard.williams@kennedy.ox.ac.uk.
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: yjwu1962@cgmh.org.tw.

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

FAP

Cancer

Name
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