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

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-D10C...

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Main Authors: 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
Format: Article
Language:English
Published: SpringerOpen 2025-06-01
Series:EJNMMI Research
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Online Access:https://doi.org/10.1186/s13550-025-01254-2
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Summary: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. Graphical abstract
ISSN:2191-219X