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Evaluation of 18F-FAPI-04 Imaging in Assessing the Therapeutic Response of Rheumatoid Arthritis

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Abstract

Purpose

Fibroblast activating protein (FAP) is highly expressed in the synovial tissues of rheumatoid arthritis (RA) patients. The aim of this study was to determine the feasibility of PET imaging with an Al[18F] F-NOTA-labeled FAP inhibitor 04(18F-FAPI-04) for the evaluation of arthritic progression and therapeutic response in experimental arthritis.

Methods

Fibroblast-like synoviocytes (FLSs) were obtained from patients with RA or osteoarthritis (OA), and the relationship between 18F-FAPI-04 uptake and the inflammatory activity of RA FLSs was investigated. Collagen-induce arthritis (CIA) mice models were established and treated with methotrexate (MTX) or etanercept (ETC). Then, PET imaging was performed 24 h following 18F-FAPI-04 injection. The imaging results were compared by assessing macroscopic arthritis scores and histological staining.

Results

18F-FAPI-04 uptake was obvious in RA FLSs that characterizing FAP activation. The higher the uptake of 18F-FAPI-04, the more severity of the inflammatory phenotype in RA FLS. Furthermore, the uptake of 18F-FAPI-04 in inflamed joints could be found even before the deformity of the parental joints could be observed by histological examination. Both MTX and ETC were effective in inhibiting the progression of arthritis in CIA mice was confirmed by macroscopic, histological, and radiographic pathology scores. Importantly, 18F-FAPI-04 uptake declined accordingly in CIA models following MTX and ETC treatment.

Conclusions

These findings suggest that PET imaging of 18F-FAPI-04 can be used to monitor treatment response in RA, and is more sensitive in disease speculation than macroscopic arthritis scoring.

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Data Availability

The data used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was funded by National Natural Science Foundation of China (Grant No. 82072850, 81772760, 82101903, 81901666, 82171801, 82271842), Natural Science Foundation of Shandong Province (Grant No. ZR2020YQ55), Key Research and Development project of Shandong Province (No. 2021ZDSYS27), The Innovation Project of Shandong Academy of Medical Sciences (2021), The Youth Innovation Technology Plan of Shandong University (Grant No. 2019KJK003), and Academic Promotion Programme of Shandong First Medical University (Grant No. 2019LJ001).

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Author notes

  1. Qingyun Zhang and Xuehong Lin contributed equally to this work.

Authors and Affiliations

  1. Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, NHC Key Laboratory of Biotechnology Drugs (Shandong Academy of Medical Sciences), Key Lab for Rare & Uncommon Diseases of Shandong Province, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China; Department of Rheumatology and Autoimmunology, The First Affiliated Hospital of Shandong First Medical University, #6699, Qingdao Road, Jinan, 250017, China

    Qingyun Zhang, Xuehong Lin, Mengxue Lü, Zhurui Shao, Dandan Shi, Ruojia Zhang, Yuang Zhang, Jihong Pan, Luna Ge, Lin Wang & Jinxiang Han

  2. College of Preventive Medical Sciences (Institute of Radiation Medicine), Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, China

    Weiqi Wang

  3. Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

    Xiaofan Zhang

  4. School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China

    Haojun Shi

  5. Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

    Guanhua Song

  6. Department of PET/CT Center, Shandong Cancer Hospital and Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji’nan 250117, Shandong, China

    Kai Cheng

Authors
  1. Qingyun Zhang
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  10. Yuang Zhang
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  13. Kai Cheng
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  14. Luna Ge
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  15. Lin Wang
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  16. Jinxiang Han
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Contributions

All authors contributed to the writing or revision of the article, and all authors approved the final publication version. In the study, Jinxiang Han had full access to all data and is responsible for the accuracy and integrity. Jinxiang Han and Lin Wang conceptualized and designed the study. Luna Ge and Lin Wang wrote the manuscript. Acquisition of data: Qingyun Zhang, Xuehong Lin, Mengxue Lü, Dandan Shi, Ruojia Zhang, Haojun Shi, Kai Cheng. Yuang Zhang, and Jihong Pan and Guanhua Song analyzed and interpreted data. Luna Ge, Lin Wang, Weiqi Wang, Xiaofan Zhang, and Zhurui Shao revised the manuscript.

Corresponding authors

Correspondence to Luna Ge, Lin Wang or Jinxiang Han.

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Zhang, Q., Lin, X., Wang, W. et al. Evaluation of 18F-FAPI-04 Imaging in Assessing the Therapeutic Response of Rheumatoid Arthritis. Mol Imaging Biol 25, 630–637 (2023). https://doi.org/10.1007/s11307-023-01817-6

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  • DOI: https://doi.org/10.1007/s11307-023-01817-6

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