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

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

doi:10.1186/s13550-025-01254-2

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

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

Research output: Contribution to journal › Article › Scientific › peer-review

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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.

Original language	English
Article number	66
Journal	EJNMMI Research
Volume	15
Issue number	1
DOIs	https://doi.org/10.1186/s13550-025-01254-2
Publication status	Published - 4 Jun 2025
MoE publication type	A1 Journal article-refereed

Funding

The study was supported financially by grants from the Jane and Aatos Erkko Foundation (to A.R.), the Finnish Foundation for Cardiovascular Research (to P.A. and\u00A0A.R.), the Research Council of Finland (#350117 to A.R.), the Sigrid Jus\u00E9lius Foundation (to A.R and A.Sa.), the Orion Research Foundation (to P.A.), and the Turku University Foundation (to P.A.). P.A. is a PhD student supported partially by the Drug Research Doctoral Programme of the University of Turku Graduate School and the doctoral module of the InFLAMES Flagship. The study was supported financially by grants from the Jane and Aatos Erkko Foundation (to A.R.), the Finnish Foundation for Cardiovascular Research (to P.A. and A.R.), the Research Council of Finland (#350117 to A.R.), the Sigrid Jus\u00E9lius Foundation (to A.R and A.Sa.), the Orion Research Foundation (to P.A.), and the Turku University Foundation (to P.A.). P.A. is a PhD student supported partially by the Drug Research Doctoral Programme of the University of Turku Graduate School and the doctoral module of the InFLAMES Flagship.

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s13550-025-01254-2Final published version, 11.2 MBLicence: CC BY

https://urn.fi/URN:NBN:fi-fe2025091195325

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Andriana, P., Palani, S., Liljenbäck, H., Iqbal, I., Oikonen, V., Virta, J., Makrypidi, K., Rajander, J., Atencio Herre, E., Suni, A., Jalkanen, S., Knuuti, J., Martinez-Pomares, L., Pirmettis, I., Li, X.-G., Saraste, A., & Roivainen, A. (2025). Macrophage mannose receptor CD206-targeted PET imaging in experimental acute myocardial infarction. EJNMMI Research, 15(1), Article 66. https://doi.org/10.1186/s13550-025-01254-2

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title = "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-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. ",

author = "Putri Andriana and Senthil Palani and Heidi Liljenb{\"a}ck and Imran Iqbal and Vesa Oikonen and Jenni Virta and Konstantina Makrypidi and Johan Rajander and \{Atencio Herre\}, Erika and Aino Suni and Sirpa Jalkanen and Juhani Knuuti and Luisa Martinez-Pomares and Ioannis Pirmettis and Xiang-Guo Li and Antti Saraste and Anne Roivainen",

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Andriana, P, Palani, S, Liljenbäck, H, Iqbal, I, Oikonen, V, Virta, J, Makrypidi, K, Rajander, J, Atencio Herre, E, Suni, A, Jalkanen, S, Knuuti, J, Martinez-Pomares, L, Pirmettis, I, Li, X-G, Saraste, A & Roivainen, A 2025, 'Macrophage mannose receptor CD206-targeted PET imaging in experimental acute myocardial infarction', EJNMMI Research, vol. 15, no. 1, 66. https://doi.org/10.1186/s13550-025-01254-2

TY - JOUR

T1 - Macrophage mannose receptor CD206-targeted PET imaging in experimental acute myocardial infarction

AU - Andriana, Putri

AU - Palani, Senthil

AU - Liljenbäck, Heidi

AU - Iqbal, Imran

AU - Oikonen, Vesa

AU - Virta, Jenni

AU - Makrypidi, Konstantina

AU - Rajander, Johan

AU - Atencio Herre, Erika

AU - Suni, Aino

AU - Jalkanen, Sirpa

AU - Knuuti, Juhani

AU - Martinez-Pomares, Luisa

AU - Pirmettis, Ioannis

AU - Li, Xiang-Guo

AU - Saraste, Antti

AU - Roivainen, Anne

PY - 2025/6/4

Y1 - 2025/6/4

N2 - 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.

AB - 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.

U2 - 10.1186/s13550-025-01254-2

DO - 10.1186/s13550-025-01254-2

M3 - Article

C2 - 40465093

SN - 2191-219X

VL - 15

JO - EJNMMI Research

JF - EJNMMI Research

IS - 1

M1 - 66

ER -

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

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