Huang Yupeng, Wu Yang, Liu Huan, Chen Yuehong, Xie Qibing, Yin Geng
Department of General Practice, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Front Immunol. 2025 Jun 18;16:1616618. doi: 10.3389/fimmu.2025.1616618. eCollection 2025.
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.
类风湿关节炎(RA)是一种以滑膜炎和关节破坏为特征的慢性炎症性疾病,仍然是一项全球性的健康挑战。活化的成纤维细胞样滑膜细胞(FLS)在RA的进展中起关键作用,表现出肿瘤样侵袭性并分泌炎症介质。成纤维细胞活化蛋白(FAP)是一种II型跨膜丝氨酸蛋白酶,在肿瘤学领域已被广泛研究数十年,并产生了显著的临床效益。FAP在肿瘤相关成纤维细胞中高度表达,在肿瘤生长、扩散和免疫逃逸中起关键作用。在癌症成像中,小分子FAP抑制剂(FAPI)PET/CT在检测原发性肿瘤和转移灶方面显示出卓越的敏感性。此外,FAP靶向放射性核素治疗已成为一种有前景的策略,可在保护健康组织的同时,将精确的辐射传递至肿瘤。除肿瘤学外,FAP在非恶性疾病中的研究也在迅速推进。在RA中,FAP在RA-FLS中过表达,但在正常组织中稀缺。因此,FAPI PET/CT可以准确显示滑膜炎并监测RA患者的治疗反应。同样,FAP成像通过绘制成纤维细胞活性来评估关节外表现,如间质性肺病和心脏纤维化,提供了一种非侵入性工具。此外,新兴疗法,如FAP靶向光动力疗法,可在RA模型中选择性消除致病细胞,凸显了其治疗潜力。本综述重点介绍了针对RA的FAP靶向成像的进展,特别关注FAP作为RA诊断、疾病评估和潜在治疗用途的关键生物标志物。