Suppr超能文献

利用 Ga 标记的成纤维细胞激活蛋白抑制剂 FAPI-04 对心肌梗死后成纤维细胞活性进行分子成像。

Molecular Imaging of Fibroblast Activity After Myocardial Infarction Using a Ga-Labeled Fibroblast Activation Protein Inhibitor, FAPI-04.

机构信息

Department of Nuclear Medicine, Klinikum rechts der Isar der TUM, Munich, Germany

Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universität, Munich, Germany.

出版信息

J Nucl Med. 2019 Dec;60(12):1743-1749. doi: 10.2967/jnumed.119.226993. Epub 2019 Aug 12.

Abstract

Heart failure remains a major source of late morbidity and mortality after myocardial infarction (MI). The temporospatial presence of activated fibroblasts in the injured myocardium predicts the quality of cardiac remodeling after MI. Therefore, monitoring of activated fibroblasts is of great interest for studying cardiac remodeling after MI. Fibroblast activation protein (FAP) expression is upregulated in activated fibroblasts. This study investigated the feasibility of imaging activated fibroblasts with a new Ga-labeled FAP inhibitor (Ga-FAPI-04) for PET imaging of fibroblast activation in a preclinical model of MI. MI and sham-operated rats were scanned with Ga-FAPI-04 PET/CT (1, 3, 6, 14, 23, and 30 d after MI) and with F-FDG (3 d after MI). Dynamic Ga-FAPI-04 PET and blocking studies were performed on MI rats 7 d after coronary ligation. After in vivo scans, the animals were euthanized and their hearts harvested for ex vivo analyses. Cryosections were prepared for autoradiography, hematoxylin and eosin (H&E), and immunofluorescence staining. Ga-FAPI-04 uptake in the injured myocardium peaked on day 6 after coronary ligation. The tracer accumulated intensely in the MI territory, as identified by decreased F-FDG uptake and confirmed by PET/MR and H&E staining. Autoradiography and H&E staining of cross-sections revealed that Ga-FAPI-04 accumulated mainly at the border zone of the infarcted myocardium. In contrast, there was only minimal uptake in the infarct of the blocked rats, comparable to the uptake in the remote noninfarcted myocardium (PET image-derived ratio of infarct uptake to remote uptake: 6 ± 2). Immunofluorescence staining confirmed the presence of FAP-positive myofibroblasts in the injured myocardium. Morphometric analysis of the whole-heart sections demonstrated 3- and 8-fold higher FAP-positive fibroblast density in the border zone than in the infarct center and remote area, respectively. Ga-FAPI-04 represents a promising radiotracer for in vivo imaging of post-MI fibroblast activation. Noninvasive imaging of activated fibroblasts may have significant diagnostic and prognostic value, which could aid clinical management of patients after MI.

摘要

心肌梗死后心力衰竭仍然是晚期发病率和死亡率的主要原因。在损伤的心肌中活化成纤维细胞的时空存在预测了心肌梗死后心脏重构的质量。因此,监测活化的成纤维细胞对于研究心肌梗死后的心脏重构具有重要意义。成纤维细胞激活蛋白 (FAP) 的表达在活化的成纤维细胞中上调。本研究旨在探讨一种新的 Ga 标记的 FAP 抑制剂 (Ga-FAPI-04) 用于心肌梗死后成纤维细胞活化的 PET 成像的可行性,该抑制剂在心肌梗死后的临床前模型中进行了研究。MI 和假手术大鼠在 MI 后 1、3、6、14、23 和 30 天用 Ga-FAPI-04 PET/CT 进行扫描,并在 MI 后 3 天用 F-FDG 进行扫描。在冠状动脉结扎后 7 天对 MI 大鼠进行动态 Ga-FAPI-04 PET 和阻断研究。在体内扫描后,将动物安乐死并取出心脏进行离体分析。制备冷冻切片进行放射自显影、苏木精和伊红 (H&E) 和免疫荧光染色。Ga-FAPI-04 在冠状动脉结扎后第 6 天在受损心肌中的摄取达到峰值。该示踪剂在 MI 区域强烈积累,这通过 F-FDG 摄取减少来确定,并通过 PET/MR 和 H&E 染色来证实。横截面的放射自显影和 H&E 染色表明,Ga-FAPI-04 主要在梗死心肌的交界区积聚。相比之下,在阻断大鼠的梗死部位仅有最小的摄取,与非梗死的远程心肌的摄取相当(PET 图像衍生的梗死摄取与远程摄取之比:6±2)。免疫荧光染色证实了损伤心肌中存在 FAP 阳性的肌成纤维细胞。全心脏切片的形态计量学分析表明,交界区的 FAP 阳性成纤维细胞密度分别比梗死中心和远程区域高 3 倍和 8 倍。Ga-FAPI-04 是一种很有前途的放射性示踪剂,可用于体内成像心肌梗死后的成纤维细胞激活。活化成纤维细胞的非侵入性成像可能具有重要的诊断和预后价值,这将有助于 MI 后患者的临床管理。

相似文献

2
Noninvasive Monitoring of Reparative Fibrosis after Myocardial Infarction in Rats Using Ga-FAPI-04 PET/CT.
Mol Pharm. 2022 Nov 7;19(11):4171-4178. doi: 10.1021/acs.molpharmaceut.2c00551. Epub 2022 Aug 15.
3
Imaging of cardiac fibroblast activation in a patient after acute myocardial infarction using Ga-FAPI-04.
J Nucl Cardiol. 2022 Oct;29(5):2254-2261. doi: 10.1007/s12350-021-02603-z. Epub 2021 Apr 15.
4
Molecular imaging of fibroblast activation protein after myocardial infarction using the novel radiotracer [Ga]MHLL1.
Theranostics. 2021 Jun 22;11(16):7755-7766. doi: 10.7150/thno.51419. eCollection 2021.
6
Ga-FAPI PET visualize heart failure: from mechanism to clinic.
Eur J Nucl Med Mol Imaging. 2023 Jan;50(2):475-485. doi: 10.1007/s00259-022-05994-4. Epub 2022 Oct 21.
7
Early detection of radiation-induced myocardial damage by [F]AlF-NOTA-FAPI-04 PET/CT imaging.
Eur J Nucl Med Mol Imaging. 2023 Jan;50(2):453-464. doi: 10.1007/s00259-022-05962-y. Epub 2022 Sep 19.
9
Cardiac fibroblast activation detected by Ga-68 FAPI PET imaging as a potential novel biomarker of cardiac injury/remodeling.
J Nucl Cardiol. 2021 Jun;28(3):812-821. doi: 10.1007/s12350-020-02307-w. Epub 2020 Sep 25.
10
Visualization of Activated Fibroblasts in Heart Failure with Preserved Ejection Fraction with [F]AlF-NOTA-FAPI-04 PET/CT Imaging.
Mol Pharm. 2023 May 1;20(5):2634-2641. doi: 10.1021/acs.molpharmaceut.3c00075. Epub 2023 Apr 12.

引用本文的文献

1
Comparison of [Ga]Ga-FAPI-04 and [F]FDG PET/CT for detection of bone metastases of lung cancer.
Quant Imaging Med Surg. 2025 Sep 1;15(9):8627-8640. doi: 10.21037/qims-2025-234. Epub 2025 Aug 18.
2
Fibrotic Disease: from Signaling Pathways and Biomarkers to Molecular Imaging.
Mol Imaging Biol. 2025 Aug 11. doi: 10.1007/s11307-025-02038-9.
3
PET Study of S1PR1 Expression in Rodent Model of Myocardial Infarction.
Mol Imaging Biol. 2025 Aug 6. doi: 10.1007/s11307-025-02039-8.
9
Molecular Imaging of Fibroblast Activation Protein in Response to Cardiac Injury Using [Ga]Ga-DATA.SA.FAPi.
Pharmaceuticals (Basel). 2025 Apr 29;18(5):658. doi: 10.3390/ph18050658.
10
Application of Ga- and Lu-Labeled FAP Inhibitor in Evaluation and Treatment of Cardiac Fibrosis After Myocardial Infarction.
MedComm (2020). 2025 May 16;6(6):e70198. doi: 10.1002/mco2.70198. eCollection 2025 Jun.

本文引用的文献

1
A novel fibroblast activation inhibitor attenuates left ventricular remodeling and preserves cardiac function in heart failure.
Am J Physiol Heart Circ Physiol. 2018 Sep 1;315(3):H563-H570. doi: 10.1152/ajpheart.00603.2017. Epub 2018 Jun 27.
2
A Tumor-Imaging Method Targeting Cancer-Associated Fibroblasts.
J Nucl Med. 2018 Sep;59(9):1423-1429. doi: 10.2967/jnumed.118.210435. Epub 2018 Apr 6.
3
Development of Quinoline-Based Theranostic Ligands for the Targeting of Fibroblast Activation Protein.
J Nucl Med. 2018 Sep;59(9):1415-1422. doi: 10.2967/jnumed.118.210443. Epub 2018 Apr 6.
4
Post-Myocardial Infarction Heart Failure.
JACC Heart Fail. 2018 Mar;6(3):179-186. doi: 10.1016/j.jchf.2017.09.015.
5
Small molecule-mediated inhibition of myofibroblast transdifferentiation for the treatment of fibrosis.
Proc Natl Acad Sci U S A. 2017 May 2;114(18):4679-4684. doi: 10.1073/pnas.1702750114. Epub 2017 Apr 17.
6
Cardiac αβ integrin expression following acute myocardial infarction in humans.
Heart. 2017 Apr;103(8):607-615. doi: 10.1136/heartjnl-2016-310115. Epub 2016 Dec 7.
7
Cardiac fibrosis in myocardial infarction-from repair and remodeling to regeneration.
Cell Tissue Res. 2016 Sep;365(3):563-81. doi: 10.1007/s00441-016-2431-9. Epub 2016 Jun 21.
8
The Living Scar--Cardiac Fibroblasts and the Injured Heart.
Trends Mol Med. 2016 Feb;22(2):99-114. doi: 10.1016/j.molmed.2015.12.006. Epub 2016 Jan 14.
9
Fibroblast activation protein alpha expression identifies activated fibroblasts after myocardial infarction.
J Mol Cell Cardiol. 2015 Oct;87:194-203. doi: 10.1016/j.yjmcc.2015.08.016. Epub 2015 Aug 28.
10
Selective Inhibitors of Fibroblast Activation Protein (FAP) with a (4-Quinolinoyl)-glycyl-2-cyanopyrrolidine Scaffold.
ACS Med Chem Lett. 2013 Mar 18;4(5):491-6. doi: 10.1021/ml300410d. eCollection 2013 May 9.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验