Bundgaard-Nielsen Mads, Johnsen Rikke Helin, Mortensen Jann, Shaker Saher Burhan, Nielsen Christoffer Tandrup Holst
Center for Rheumatology and Spine Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Department for Respiratory Medicine and Infectious Diseases, Copenhagen University Hospital - North Zealand Hospital, Hilleroed, Denmark.
Autoimmun Rev. 2025 Aug 29;24(9):103856. doi: 10.1016/j.autrev.2025.103856. Epub 2025 Jun 20.
Currently, no tools can monitor ongoing fibrotic activity properly, making early identification of and timely therapeutic intervention with antifibrotics in patients with progressive fibrosing interstitial lung disease (ILD) difficult. Fibroblast activation protein-α inhibitor (FAPI) radiotracers could address these challenges.
This review examines the association between pulmonary FAPI tracer uptake, fibrotic activity, and clinical parameters used for disease monitoring and prognostication in ILD to provide insights into its clinical potential.
In January 2025, a systematic literature search on PubMed, Ovid Medline, and Cochrane Library, utilizing the block-search strategy and snowballing, was conducted, and 13 studies were included.
Both murine and human studies support that FAPI tracer uptake reflects fibrotic activity in ILDs, as uptake was consistently elevated in subject groups compared to controls. In murine ILD models, increased uptake was associated with fibrosis and fibroblast activation protein-α (FAP-α) expression upon histological examination. Uptake preceded the development of fibrosis on computed tomography (CT) and attenuated once fibrosis was established. In human ILD patients (Idiopathic pulmonary fibrosis (IPF) = 55, Connective tissue disease (CTD) ILD = 68, other ILDs = 55), FAPI uptake was localized to fibrotic lesions on high-resolution computed tomography (HRCT) and associated with increased FAP-α expression ex vivo. Uptake correlated with baseline pulmonary function tests (PFTs) and fibrosis extent on HRCT. Increased FAPI tracer uptake at baseline predicted disease progression upon follow-up.
An increasing body of evidence supports that FAPI tracers hold great clinical potential for the management of ILD by accurately monitoring fibrotic disease activity and identifying patients at risk of progression. Further research is required to confirm these findings.
目前，尚无工具能够恰当地监测正在进行的纤维化活动，这使得在进行性纤维化间质性肺疾病（ILD）患者中早期识别并及时采用抗纤维化药物进行治疗干预变得困难。成纤维细胞活化蛋白-α抑制剂（FAPI）放射性示踪剂可以应对这些挑战。
本综述探讨肺部FAPI示踪剂摄取、纤维化活动以及用于ILD疾病监测和预后评估的临床参数之间的关联，以深入了解其临床潜力。
2025年1月，利用分块搜索策略和滚雪球法在PubMed、Ovid Medline和Cochrane图书馆进行了系统的文献检索，纳入了13项研究。
小鼠和人类研究均支持FAPI示踪剂摄取反映了ILD中的纤维化活动，因为与对照组相比，研究对象组的摄取量持续升高。在小鼠ILD模型中，组织学检查显示摄取增加与纤维化和成纤维细胞活化蛋白-α（FAP-α）表达相关。在计算机断层扫描（CT）上，摄取增加先于纤维化的发展，而一旦纤维化形成，摄取就会减弱。在人类ILD患者（特发性肺纤维化（IPF）=55例，结缔组织病（CTD）相关ILD=68例，其他ILD=55例）中，FAPI摄取在高分辨率计算机断层扫描（HRCT）上定位于纤维化病变，并且与体外FAP-α表达增加相关。摄取与基线肺功能测试（PFT）和HRCT上的纤维化程度相关。基线时FAPI示踪剂摄取增加预示着随访时疾病进展。
越来越多的证据支持FAPI示踪剂通过准确监测纤维化疾病活动和识别有疾病进展风险的患者，在ILD管理方面具有巨大的临床潜力。需要进一步的研究来证实这些发现。
