放射性核素标记的成纤维细胞活化蛋白抑制剂正电子发射断层扫描在心脏疾病诊断中的研究进展

doi:10.16150/j.1671-2870.2025.02.014

摘要/Abstract

摘要：

成纤维细胞活化蛋白（fibroblast activation protein， FAP）作为一种特异性表达于活化心肌成纤维细胞（cardiac fibroblasts， CFs）表面的Ⅱ型跨膜丝氨酸蛋白酶，在心肌损伤、炎症及纤维化过程中，通过降解细胞外基质和激活转化生长因子β（transforming growth factor-β， TGF-β）等关键通路，驱动心肌间质重塑及胶原沉积，成为心肌纤维化发展的核心效应靶点。FAP仅在活化的CFs中显著上调，在但正常心肌组织中很少表达，这为心肌疾病的无创精准诊断提供了分子基础。近年来，放射性核素标记的FAP抑制剂（FAP inhibitor， FAPI）正电子发射断层扫描（positron emission tomography， PET）技术凭借其无创性、高靶向性和定量评估能力，可在分子层面早期捕获微纤维化信号，突破了传统影像（如心脏磁共振）对结构性改变的依赖，在活动性心肌纤维化的动态评估中展现出独特优势，为心脏疾病的早期诊断、病理机制探索及预后评估提供了新路径。当前研究证实，FAPI-PET在多种心脏疾病中具有重要应用价值，如在急性心肌梗死后左心室重构中动态监测梗死周边区FAP活性，可预测心室扩张及不良重构的趋势；针对放化疗及免疫治疗心脏毒性导致的亚临床纤维化实现早期预警；对于心脏淀粉样变性，可帮助早期量化评估心肌纤维化负荷，并协助评估不同亚型的危险分层和预后；在肺动脉高压及右心室重构中，可全面评估弥漫性纤维化，并显示疾病严重程度；针对不同亚型心肌病（如肥厚型/扩张型等），通过分析纤维化空间分布辅助临床表型的判断；还可评估房颤导管消融术后心房损伤修复反应，以预测心律失常复发风险。本文综述FAPI-PET检查在心脏疾病诊断中应用的国内外研究进展，展望其应用潜力与未来挑战。

关键词: 成纤维细胞活化蛋白, 心肌纤维化, 心肌损伤, 心室重塑, 细胞外基质

Abstract:

Fibroblast activation protein (FAP) is a type Ⅱ transmembrane serine protease specifically expressed on the surface of activated cardiac fibroblasts (CFs). During myocardial injury, inflammation, and fibrosis, it drives myocardial interstitial remodeling and collagen deposition by degrading the extracellular matrix and activating key pathways such as transforming growth factor-β (TGF-β), thus serving as a central effector target in the development of myocardial fibrosis. FAP is significantly upregulated exclusively in activated CFs, with minimal expression in normal myocardial tissue, provi-ding a molecular basis for the non-invasive and precise diagnosis of cardiac diseases. In recent years, radionuclide-labeled FAP inhibitor (FAPI) positron emission tomography (PET), with its non-invasiveness, high targeting specificity, and quantitative evaluation capability, has enabled the early detection of microfibrosis signals at the molecular level. This technique overcomes the reliance of conventional imaging (e.g., cardiac magnetic resonance) on structural changes, demonstrating unique advantages in the dynamic evaluation of active myocardial fibrosis and providing a novel pathway for early diagnosis, exploration of pathological mechanisms, and prognostic evaluation of cardiac diseases. Current research confirms that FAPI-PET holds significant application value across multiple cardiac diseases. For example, in left ventricular remodeling after acute myocardial infarction, dynamic monitoring of FAP activity in the peri-infarct zone can predict ventricular dilation and adverse remodeling trends. In cardiotoxicity induced by radiotherapy, chemotherapy, or immunotherapy, it achieves early warning of subclinical fibrosis. For cardiac amyloidosis, it facilitates early quantification of myocardial fibrotic burden and assists in risk stratification and prognosis evaluation across different subtypes. In pulmonary hypertension and right ventricular remodeling, it can comprehensively evaluate diffuse fibrosis and reflect the severity of the di-sease. For different subtypes of cardiomyopathy (e.g., hypertrophic/dilated), it assists in clinical phenotype identification by analyzing the spatial distribution of fibrosis. Additionally, it can be used to evaluate the atrial injury repair responses after catheter ablation for atrial fibrillation, thereby predicting the risk of arrhythmia recurrence. This study reviews domestic and international research advances in the application of FAPI-PET in the diagnosis of cardiac diseases, and discusses its application potential and future challenges.

Key words: Fibroblast activation protein, Myocardial fibrosis, Myocardial injury, Ventricular remodeling, Extracellular matrix

中图分类号:

R541

贾迎起, 张敏, 李彪. 放射性核素标记的成纤维细胞活化蛋白抑制剂正电子发射断层扫描在心脏疾病诊断中的研究进展[J]. 诊断学理论与实践, 2025, 24(02): 220-225.

JIA Yingqi, ZHANG Min, LI Biao. Research progress on positron emission tomography using radionuclide-labeled fibroblast activation protein inhibitor in diagnosis of cardiac diseases[J]. Journal of Diagnostics Concepts & Practice, 2025, 24(02): 220-225.

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