Radio-labelled fibroblast activation protein inhibitors in interstitial lung diseases - a systematic review.

IF 9.2 1区医学 Q1 IMMUNOLOGY

Autoimmunity reviews Pub Date : 2025-06-20 DOI:10.1016/j.autrev.2025.103856

Mads Bundgaard Nielsen, Rikke Helin Johnsen, Jann Mortensen, Saher Burhan Shaker, Christoffer Tandrup Holst Nielsen

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引用次数: 0

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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放射性标记成纤维细胞活化蛋白抑制剂在间质性肺疾病中的应用综述

背景：目前，没有工具可以适当地监测正在进行的纤维化活动，这使得进展性纤维化间质性肺疾病（ILD）患者的早期识别和及时的抗纤维化药物治疗干预变得困难。成纤维细胞活化蛋白-α抑制剂（FAPI）放射性示踪剂可以解决这些挑战。目的：本综述探讨肺FAPI示踪剂摄取、纤维化活性和用于ILD疾病监测和预后的临床参数之间的关系，以深入了解其临床潜力。方法：于2025年1月对PubMed、Ovid Medline和Cochrane Library进行系统文献检索，采用分组检索策略和滚雪球法，纳入13项研究。结果：小鼠和人类的研究都支持FAPI示踪剂的摄取反映了ild的纤维化活性，因为与对照组相比，受试者组的摄取持续升高。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)表达有关。在计算机断层扫描（CT）上，摄取先于纤维化的发展，并在纤维化建立后减弱。在人类ILD患者（特发性肺纤维化（IPF） = 55，结缔组织病（CTD） ILD = 68，其他ILD = 55）中，高分辨率计算机断层扫描（HRCT）显示，FAPI摄取局限于纤维化病变，并与体外FAP-α表达增加相关。摄取与基线肺功能测试（PFTs）和HRCT纤维化程度相关。基线时FAPI示踪剂摄取增加预测随访时疾病进展。结论：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进展风险的患者，在ILD的管理中具有巨大的临床潜力。需要进一步的研究来证实这些发现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Autoimmunity reviews 医学-免疫学

CiteScore

24.70

自引率

4.40%

发文量

164

审稿时长

21 days

期刊介绍： Autoimmunity Reviews is a publication that features up-to-date, structured reviews on various topics in the field of autoimmunity. These reviews are written by renowned experts and include demonstrative illustrations and tables. Each article will have a clear "take-home" message for readers. The selection of articles is primarily done by the Editors-in-Chief, based on recommendations from the international Editorial Board. The topics covered in the articles span all areas of autoimmunology, aiming to bridge the gap between basic and clinical sciences. In terms of content, the contributions in basic sciences delve into the pathophysiology and mechanisms of autoimmune disorders, as well as genomics and proteomics. On the other hand, clinical contributions focus on diseases related to autoimmunity, novel therapies, and clinical associations. Autoimmunity Reviews is internationally recognized, and its articles are indexed and abstracted in prestigious databases such as PubMed/Medline, Science Citation Index Expanded, Biosciences Information Services, and Chemical Abstracts.