Macrophage mannose receptor CD206-targeted PET imaging in experimental acute myocardial infarction.

IF 3.1 3区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

EJNMMI Research Pub Date : 2025-06-04 DOI:10.1186/s13550-025-01254-2

Putri Andriana, Senthil Palani, Heidi Liljenbäck, Imran Iqbal, Vesa Oikonen, Jenni Virta, Konstantina Makrypidi, Johan Rajander, Erika Atencio Herre, Aino Suni, Sirpa Jalkanen, Juhani Knuuti, Luisa Martinez-Pomares, Ioannis Pirmettis, Xiang-Guo Li, Antti Saraste, Anne Roivainen

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引用次数: 0

Abstract

Background: The macrophage mannose receptor (CD206) is expressed predominantly on the surface of M2-type macrophages, which play a role in resolution of inflammation after myocardial injury. The purpose of this study was to evaluate the utility of CD206-targeted PET tracer Al[¹⁸F]F-NOTA-D10CM, a fluorinated mannosylated dextran derivative, for imaging immune responses after experimental acute myocardial infarction (MI).

Results: Flow cytometry revealed selective binding of Alexa-488-NOTA-D10CM to human M2-polarized macrophages derived from blood monocytes compared to M1 macrophages. The binding affinity of Al[¹⁸F]F-NOTA-DCM for CD206-positive Chinese hamster ovary cells was 1.83 ± 0.68 nM. In vivo PET and ex vivo autoradiography experiments in Sprague-Dawley rats studied at 3 and 7 days after permanent ligation of the left coronary artery or a sham-operation, showed significantly higher uptake of Al[¹⁸F]F-NOTA-DCM in the MI area than in remote areas, or the myocardium of sham-operated rats. However, there was no difference in uptake in the MI area between day 3 and day 7. Uptake of Al[¹⁸F]F-NOTA-DCM in the MI area correlated positively with the area-% of CD206-positive staining of the left ventricular myocardium (r = 0.481, P = 0.006). In vitro competition studies on tissue cryosections using a molar excess of unlabeled D10CM revealed a reduction of approximately 85%, confirming specific tracer binding.

Conclusion: Al[¹⁸F]F-NOTA-D10CM PET detects overexpression of CD206 after ischemic myocardial injury, and may be a suitable biomarker for detecting M2-type macrophages associated with the inflammatory process post-MI.

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巨噬细胞甘露糖受体cd206靶向PET成像在实验性急性心肌梗死中的应用。

背景：巨噬细胞甘露糖受体（CD206）主要表达于m2型巨噬细胞表面，在心肌损伤后炎症的消退中发挥作用。本研究的目的是评估cd206靶向PET示踪剂Al[18F]F-NOTA-D10CM（一种氟化甘露糖基化葡聚糖衍生物）在实验性急性心肌梗死（MI）后免疫反应成像中的应用价值。结果：流式细胞术显示，与M1巨噬细胞相比，Alexa-488-NOTA-D10CM可选择性结合来自血液单核细胞的人m2极化巨噬细胞。Al[18F]F-NOTA-DCM对cd206阳性的中国仓鼠卵巢细胞的结合亲和力为1.83±0.68 nM。在左冠状动脉永久性结扎或假手术后3天和7天进行的Sprague-Dawley大鼠体内PET和离体放射自显像实验显示，心肌梗死区Al[18F]F-NOTA-DCM的摄取明显高于其他部位或假手术大鼠的心肌。然而，在第3天和第7天之间，心肌梗死区域的摄取没有差异。心肌梗死区Al[18F]F-NOTA-DCM摄取与左心室cd206阳性染色面积%呈正相关（r = 0.481, P = 0.006）。使用摩尔过量的未标记D10CM进行组织冷冻的体外竞争研究显示，减少了约85%，证实了特异性示踪剂结合。结论：Al[18F]F-NOTA-D10CM PET检测缺血心肌损伤后CD206过表达，可能是检测心肌梗死后炎症过程相关的m2型巨噬细胞的合适生物标志物。

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

EJNMMI Research RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING&nb-

CiteScore

5.90

自引率

3.10%

发文量

审稿时长

13 weeks

期刊介绍： EJNMMI Research publishes new basic, translational and clinical research in the field of nuclear medicine and molecular imaging. Regular features include original research articles, rapid communication of preliminary data on innovative research, interesting case reports, editorials, and letters to the editor. Educational articles on basic sciences, fundamental aspects and controversy related to pre-clinical and clinical research or ethical aspects of research are also welcome. Timely reviews provide updates on current applications, issues in imaging research and translational aspects of nuclear medicine and molecular imaging technologies. The main emphasis is placed on the development of targeted imaging with radiopharmaceuticals within the broader context of molecular probes to enhance understanding and characterisation of the complex biological processes underlying disease and to develop, test and guide new treatment modalities, including radionuclide therapy.