心血管成纤维细胞显像的现状和展望

doi:10. 3969/ j. issn. 1006-7795. 2024. 01. 009

摘要/Abstract

摘要： 心肌纤维化是众多心血管疾病共同的基础病理改变，与心脏不良预后密切相关。目前临床上评价心肌纤维化的技术存在有创、特异性欠佳、无法早期诊断等不足。近年来，靶向活化成纤维细胞的核素显像因其在检测心肌纤维化以及在评估疾病进展和治疗反应方面的潜力而受到人们的关注。本文结合现有研究，重点介绍其应用现状、优势和局限性，探讨其在心血管疾病中的前景，旨在为进一步推动靶向活化成纤维细胞的核素显像在心血管疾病中的应用提供参考和启示。

关键词: 心血管疾病, 成纤维细胞活化蛋白抑制剂, 心肌纤维化, 分子显像

Abstract: Myocardial fibrosis is a common pathological basis of many cardiovascular diseases and is closely related to poor prognosis of the cardiac disease. At present,there are limitations in clinical evaluation techniques for myocardial fibrosis,such as being invasive,lacking specificity,and unable to diagnose early. In recent years,nuclide imaging targeting activated fibroblasts has received attention for its potential in detecting myocardial fibrosis and in evaluating disease progression and treatment response. Based on the existing studies,the present paper focuses on its application status,advantages and limitations,and discusses its prospects in cardiovascular diseases,aiming to provide reference and inspiration to promote the application of targeted activated fibroblast radionuclide imaging in cardiovascular diseases.

Key words: cardiovascular diseases, fibroblast activation protein inhibitor, myocardial fibrosis, molecular imaging

中图分类号:

R541
R445

李丽娜, 杨敏福. 心血管成纤维细胞显像的现状和展望[J]. 首都医科大学学报, 2024, 45(1): 46-51.

Li Lina, Yang Minfu. Current status and prospect of cardiovascular fibroblast imaging[J]. Journal of Capital Medical University, 2024, 45(1): 46-51.

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链接本文: https://journal03.magtech.org.cn/Jweb_sdykdxxb/CN/10. 3969/ j. issn. 1006-7795. 2024. 01. 009

https://journal03.magtech.org.cn/Jweb_sdykdxxb/CN/Y2024/V45/I1/46

参考文献

［1］《中国心血管健康与疾病报告》编写组.《中国心血管健康与疾病报告2021》概述［J］.中国心血管病研究，2022，20（7）：577-596.
［2］Avery D, Govindaraju P, Jacob M, et al. Extracellular matrix directs phenotypic heterogeneity of activated fibroblasts［J］. Matrix Biol, 2018, 67: 90-106.
［3］Nagaraju C K, Robinson E L, Abdesselem M, et al. Myofibroblast phenotype and reversibility of fibrosis in patients with end-stage heart failure［J］. J Am Coll Cardiol, 2019, 73(18): 2267-2282.
［4］Kong P, Christia P, Frangogiannis N G. The pathogenesis of cardiac fibrosis［J］. Cell Mol Life Sci, 2014, 71(4): 549-574.
［5］Bing R, Dweck M R. Myocardial fibrosis: why image, how to image and clinical implications［J］. Heart, 2019, 105(23): 1832-1840.
［6］Raina S, Lensing S Y, Nairooz R S, et al. Prognostic value of late gadolinium enhancement CMR in systemic amyloidosis［J］. JACC Cardiovasc Imaging, 2016, 9(11): 1267-1277.
［7］Aghajanian H, Kimura T, Rurik J G, et al. Targeting cardiac fibrosis with engineered T cells［J］. Nature, 2019, 573(7774): 430-433.
［8］Ambale-Venkatesh B, Lima J A C. Cardiac MRI: a central prognostic tool in myocardial fibrosis［J］. Nat Rev Cardiol, 2015, 12(1): 18-29.
［9］Mewton N, Liu C Y, Croisille P, et al. Assessment of myocardial fibrosis with cardiovascular magnetic resonance［J］. J Am Coll Cardiol, 2011, 57(8): 891-903.
［10］Gupta S, Ge Y, Singh A, et al. Multimodality imaging assessment of myocardial fibrosis［J］. JACC Cardiovasc Imaging, 2021, 14(12): 2457-2469.
［11］Frangogiannis N G. Cardiac fibrosis［J］. Cardiovasc Res, 2021, 117(6): 1450-1488.
［12］Serruys P W, Hara H, Garg S, et al. Coronary computed tomographic angiography for complete assessment of coronary artery disease: JACC state-of-the-art review［J］. J Am Coll Cardiol, 2021, 78(7): 713-736.
［13］Luis S A, Chan J, Pellikka P A. Echocardiographic assessment of left ventricular systolic function: an overview of contemporary techniques, including speckle-tracking echocardiography［J］. Mayo Clin Proc, 2019, 94(1): 125-138.
［14］Weber K T. Cardiac interstitium in health and disease: the fibrillar collagen network［J］. J Am Coll Cardiol, 1989, 13(7): 1637-1652.
［15］Lajiness J D, Conway S J. Origin, development, and differentiation of cardiac fibroblasts［J］. J Mol Cell Cardiol, 2014, 70: 2-8.
［16］Luo Y P, Pan Q Q, Yang H X, et al. Fibroblast activation protein-targeted PET/CT with ⁶⁸Ga-FAPI for imaging IgG4-Related disease: comparison to ¹⁸F-FDG PET/CT［J］. J Nucl Med, 2021, 62(2): 266-271.
［17］Rosenkrans Z T, Massey C F, Bernau K, et al. ［⁶⁸Ga］ Ga-FAPI-46 PET for non-invasive detection of pulmonary fibrosis disease activity［J］. Eur J Nucl Med Mol Imaging, 2022, 49(11): 3705-3716.
［18］Zhou Y, Yang X, Liu H P, et al. Value of ［⁶⁸Ga］ Ga-FAPI-04 imaging in the diagnosis of renal fibrosis［J］. Eur J Nucl Med Mol Imaging, 2021, 48(11): 3493-3501.
［19］Pirasteh A, Periyasamy S, Meudt J J, et al. Staging liver fibrosis by fibroblast activation protein inhibitor PET in a human-sized swine model［J］. J Nucl Med, 2022, 63(12): 1956-1961.
［20］Xie B Q, Wang J X, Xi X Y, et al. Fibroblast activation protein imaging in reperfused ST-elevation myocardial infarction: comparison with cardiac magnetic resonance imaging［J］. Eur J Nucl Med Mol Imaging, 2022, 49(8): 2786-2797.
［21］Chen B X, Xing H Q, Gong J N, et al. Imaging of cardiac fibroblast activation in patients with chronic thromboembolic pulmonary hypertension［J］. Eur J Nucl Med Mol Imaging, 2022, 49(4): 1211-1222.
［22］Heckmann M B, Reinhardt F, Finke D, et al. Relationship between cardiac fibroblast activation protein activity by positron emission tomography and cardiovascular disease［J］. Circ Cardiovasc Imaging, 2020, 13(9): e010628.
［23］Wang L, Wang Y L, Wang J, et al. Myocardial activity at ¹⁸F-FAPI PET/CT and risk for sudden cardiac death in hypertrophic cardiomyopathy［J］. Radiology, 2023, 306(2): e221052.
［24］Varasteh Z, Mohanta S, Robu S, et al. Molecular imaging of fibroblast activity after myocardial infarction using a ⁶⁸Ga-Labeled fibroblast activation protein inhibitor, FAPI-04［J］. J Nucl Med, 2019, 60(12): 1743-1749.
［25］Qiao P, Wang Y, Zhu K, et al. Noninvasive monitoring of reparative fibrosis after myocardial infarction in rats using ⁶⁸Ga-FAPI-04 PET/CT［J］. Mol Pharm, 2022, 19(11): 4171-4178.
［26］Notohamiprodjo S, Nekolla S G, Robu S, et al. Imaging of cardiac fibroblast activation in a patient after acute myocardial infarction using ⁶⁸Ga-FAPI-04［J］. J Nucl Cardiol, 2022, 29(5): 2254-2261.
［27］Kessler L, Kupusovic J, Ferdinandus J, et al. Visualization of fibroblast activation after myocardial infarction using ⁶⁸Ga-FAPI PET［J］. Clin Nucl Med, 2021, 46(10): 807-813.
［28］Zhang M, Quan W, Zhu T, et al. ［⁶⁸Ga］ Ga-DOTA-FAPI-04 PET/MR in patients with acute myocardial infarction: potential role of predicting left ventricular remodeling［J］. Eur J Nucl Med Mol Imaging, 2023, 50(3): 839-848.
［29］Diekmann J, Koenig T, Thackeray J T, et al. Cardiac fibroblast activation in patients early after acute myocardial infarction: integration with mr tissue characterization and subsequent functional outcome［J］. J Nucl Med, 2022, 63(9): 1415-1423.
［30］Totzeck M, Siebermair J, Rassaf T, et al. Cardiac fibroblast activation detected by positron emission tomography/computed tomography as a possible sign of cardiotoxicity［J］. Eur Heart J, 2020, 41(9): 1060.
［31］Niu N, Huo L, Zhang S, et al. Immune checkpoint inhibitor-associated cardiotoxicity detected by ⁶⁸Ga-DOTATATE PET/CT and ⁶⁸Ga-FAPI PET/CT［J］. Eur Heart J Cardiovasc Imaging, 2022, 23(3): e123.
［32］Finke D, Heckmann M B, Herpel E, et al. Early detection of checkpoint inhibitor-associated myocarditis using ⁶⁸Ga-FAPI PET/CT［J］. Front Cardiovasc Med, 2021: 8, 614997.
［33］Wei Y C, Sun Y H, Liu J Y, et al. Early detection of radiation-induced myocardial damage by ［¹⁸F］AlF-NOTA-FAPI-04 PET/CT imaging［J］. Eur J Nucl Med Mol Imaging, 2023, 50(2): 453-464.
［34］Zhang Y, Dong Z, Wang L, et al. Functional significance of myocardial activity at ¹⁸F-FAPI PET/CT in hypertrophic cardiomyopathy identified by cardiac magnetic resonance feature-tracking strain analysis［J］. Eur J Nucl Med Mol Imaging, 2023, 51(1): 110-122.
［35］Song W Y, Zhang X, He S K, et al. ⁶⁸Ga-FAPI PET visualize heart failure: from mechanism to clinic［J］. Eur J Nucl Med Mol Imaging, 2023, 50(2): 475-485.
［36］Xie B Q, Li L N, Lin M M, et al. ⁹⁹mTc-HFAPi imaging identifies early myocardial fibrosis in the hypertensive heart［J］. J Hypertens, 2023, 41(10): 1645-1652.
［37］Xi X Y, Wang L, Liu A J, et al. Myocardial fibroblast activation imaging in light chain cardiac amyloidosis［J］. J Nucl Cardiol, 2023, 30(4): 1690-1692.
［38］Siebermair J, Kessler L, Kupusovic J, et al. Cardiac fibroblast activation detected by ⁶⁸Gallium-FAPI-46 positron emission tomography-magnetic resonance imaging as a sign of chronic activity in cardiac sarcoidosis［J］. Eur Heart J Case Rep, 2022, 6(1): ytac005.
［39］Treutlein C, Distler J H W, Tascilar K, et al. Assessment of myocardial fibrosis in patients with systemic sclerosis using ［⁶⁸Ga］ Ga-FAPI-04-PET-CT［J］. Eur J Nucl Med Mol Imaging, 2023, 50(6): 1629-1635.
［40］Wu S M, Pang Y Z, Zhao L, et al. ⁶⁸Ga-FAPI PET/CT versus ¹⁸F-FDG PET/CT for the evaluation of disease activity in takayasu arteritis［J］. Clin Nucl Med, 2021, 46(10): 847-849.
［41］Gong J N, Chen B X, Xing H Q, et al. Pulmonary artery imaging with ⁶⁸Ga-FAPI-04 in patients with chronic thromboembolic pulmonary hypertension［J］. J Nucl Cardiol, 2023, 30(3): 1166-1172.
［42］Kupusovic J, Kessler L, Nekolla S G, et al. Visualization of thermal damage using ⁶⁸Ga-FAPI-PET/CT after pulmonary vein isolation［J］. Eur J Nucl Med Mol Imaging, 2022, 49(5): 1553-1559.
［43］Wu M Q, Ning J, Li J L, et al. Feasibility of in vivo imaging of fibroblast activation protein in human arterial walls［J］. J Nucl Med, 2022, 63(6): 948-951.