Targeting fibroblast activation protein in rheumatoid arthritis: from molecular imaging to precision therapeutics
Rheumatoid arthritis (RA), a chronic inflammatory disorder characterized by synovitis and joint destruction, remains a global health challenge. Activated fibroblast-like synoviocytes (FLS), which play a crucial role in the progression of RA, demonstrate tumor-like invasiveness and secrete inflammato...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1616618/full |
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| author | Yupeng Huang Yang Wu Huan Liu Yuehong Chen Qibing Xie Geng Yin |
| author_facet | Yupeng Huang Yang Wu Huan Liu Yuehong Chen Qibing Xie Geng Yin |
| author_sort | Yupeng Huang |
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| description | Rheumatoid arthritis (RA), a chronic inflammatory disorder characterized by synovitis and joint destruction, remains a global health challenge. Activated fibroblast-like synoviocytes (FLS), which play a crucial role in the progression of RA, demonstrate tumor-like invasiveness and secrete inflammatory mediators. Fibroblast activation protein (FAP), a type II transmembrane serine protease, has been extensively studied in oncology for decades and has yielded significant clinical benefits. FAP is highly expressed in tumor-associated fibroblasts and plays a pivotal role in tumor growth, dissemination, and immune escape. In cancer imaging, small-molecule FAP inhibitor (FAPI) PET/CT has demonstrated superior sensitivity for detecting primary tumors and metastases. Additionally, FAP-targeted radionuclide therapy has emerged as a promising strategy for delivering precise radiation to tumors, while sparing healthy tissues. Beyond oncology, research on FAP in non-malignant diseases is rapidly advancing. In RA, FAP is overexpressed in RA-FLS but scarce in normal tissues. Thus, FAPI PET/CT can accurately visualize synovitis and monitor the treatment response in patients with RA. Similarly, FAP imaging is used to assess extra-articular manifestations, such as interstitial lung disease and cardiac fibrosis, by mapping fibroblast activity, offering a non-invasive tool. Moreover, emerging therapies, such as FAP-targeted photodynamic therapy, selectively eliminate pathogenic cells in RA models, highlighting their therapeutic potential. This review highlights the advances in FAP-targeted imaging for RA, specifically focusing on FAP as a key biomarker for diagnosis, disease evaluation, and potential therapeutic use in RA. |
| format | Article |
| id | doaj-art-d18da9ecda7e45ba972756334e316e63 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-d18da9ecda7e45ba972756334e316e632025-08-20T02:35:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.16166181616618Targeting fibroblast activation protein in rheumatoid arthritis: from molecular imaging to precision therapeuticsYupeng Huang0Yang Wu1Huan Liu2Yuehong Chen3Qibing Xie4Geng Yin5Department of General Practice, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of General Practice, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of General Practice, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaRheumatoid arthritis (RA), a chronic inflammatory disorder characterized by synovitis and joint destruction, remains a global health challenge. Activated fibroblast-like synoviocytes (FLS), which play a crucial role in the progression of RA, demonstrate tumor-like invasiveness and secrete inflammatory mediators. Fibroblast activation protein (FAP), a type II transmembrane serine protease, has been extensively studied in oncology for decades and has yielded significant clinical benefits. FAP is highly expressed in tumor-associated fibroblasts and plays a pivotal role in tumor growth, dissemination, and immune escape. In cancer imaging, small-molecule FAP inhibitor (FAPI) PET/CT has demonstrated superior sensitivity for detecting primary tumors and metastases. Additionally, FAP-targeted radionuclide therapy has emerged as a promising strategy for delivering precise radiation to tumors, while sparing healthy tissues. Beyond oncology, research on FAP in non-malignant diseases is rapidly advancing. In RA, FAP is overexpressed in RA-FLS but scarce in normal tissues. Thus, FAPI PET/CT can accurately visualize synovitis and monitor the treatment response in patients with RA. Similarly, FAP imaging is used to assess extra-articular manifestations, such as interstitial lung disease and cardiac fibrosis, by mapping fibroblast activity, offering a non-invasive tool. Moreover, emerging therapies, such as FAP-targeted photodynamic therapy, selectively eliminate pathogenic cells in RA models, highlighting their therapeutic potential. This review highlights the advances in FAP-targeted imaging for RA, specifically focusing on FAP as a key biomarker for diagnosis, disease evaluation, and potential therapeutic use in RA.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1616618/fullrheumatoid arthritisfibroblast activation proteinFAPIdisease evaluationtreatment |
| spellingShingle | Yupeng Huang Yang Wu Huan Liu Yuehong Chen Qibing Xie Geng Yin Targeting fibroblast activation protein in rheumatoid arthritis: from molecular imaging to precision therapeutics Frontiers in Immunology rheumatoid arthritis fibroblast activation protein FAPI disease evaluation treatment |
| title | Targeting fibroblast activation protein in rheumatoid arthritis: from molecular imaging to precision therapeutics |
| title_full | Targeting fibroblast activation protein in rheumatoid arthritis: from molecular imaging to precision therapeutics |
| title_fullStr | Targeting fibroblast activation protein in rheumatoid arthritis: from molecular imaging to precision therapeutics |
| title_full_unstemmed | Targeting fibroblast activation protein in rheumatoid arthritis: from molecular imaging to precision therapeutics |
| title_short | Targeting fibroblast activation protein in rheumatoid arthritis: from molecular imaging to precision therapeutics |
| title_sort | targeting fibroblast activation protein in rheumatoid arthritis from molecular imaging to precision therapeutics |
| topic | rheumatoid arthritis fibroblast activation protein FAPI disease evaluation treatment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1616618/full |
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