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Journal of Nuclear Medicine

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Research ArticleCardiovascular

Targeted PET Imaging of Chemokine Receptor 2–Positive Monocytes and Macrophages in the Injured Heart

Gyu Seong Heo, Geetika Bajpai, Wenjun Li, Hannah P. Luehmann, Deborah H. Sultan, Hao Dun, Florian Leuschner, Steven L. Brody, Robert J. Gropler, Daniel Kreisel, Kory J. Lavine and Yongjian Liu
Journal of Nuclear Medicine January 2021, 62 (1) 111-114; DOI: https://doi.org/10.2967/jnumed.120.244673
Gyu Seong Heo
1Department of Radiology, Washington University School of Medicine, St. Louis, Missouri
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Geetika Bajpai
2Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
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Wenjun Li
3Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
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Hannah P. Luehmann
1Department of Radiology, Washington University School of Medicine, St. Louis, Missouri
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Deborah H. Sultan
1Department of Radiology, Washington University School of Medicine, St. Louis, Missouri
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Hao Dun
2Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
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Florian Leuschner
4Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany
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Steven L. Brody
1Department of Radiology, Washington University School of Medicine, St. Louis, Missouri
2Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
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Robert J. Gropler
1Department of Radiology, Washington University School of Medicine, St. Louis, Missouri
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Daniel Kreisel
3Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
4Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany
5Department of Immunology and Pathology, Washington University School of Medicine, St. Louis, Missouri; and
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Kory J. Lavine
2Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
5Department of Immunology and Pathology, Washington University School of Medicine, St. Louis, Missouri; and
6Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri
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Yongjian Liu
1Department of Radiology, Washington University School of Medicine, St. Louis, Missouri
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Abstract

Proinflammatory macrophages are important mediators of inflammation after myocardial infarction and of allograft injury after heart transplantation. The aim of this study was to image the recruitment of proinflammatory chemokine receptor 2–positive (CCR2+) cells in multiple heart injury models. Methods: 64Cu-DOTA-extracellular loop 1 inverso (ECL1i) PET was used to image CCR2+ monocytes and macrophages in a heart transplantation mouse model. Flow cytometry was performed to characterize CCR2+ cells. Autoradiography on a human heart specimen was conducted to confirm binding specificity. 64Cu- and 68Ga-DOTA-ECL1i were compared in an ischemia–reperfusion injury mouse model. Results: 64Cu-DOTA-ECL1i showed sensitive and specific detection of CCR2+ cells in all tested mouse models, with efficacy comparable to that of 68Ga-DOTA-ECL1i. Flow cytometry demonstrated specific expression of CCR2 on monocytes and macrophages. The tracer binds to human CCR2. Conclusion: This work establishes the utility of 64Cu-DOTA-ECL1i to image CCR2+ monocytes and macrophages in mouse models and provides the requisite preclinical information to translate the targeted clinical-grade CCR2 imaging probe for clinical investigation of heart diseases.

  • PET
  • C-C chemokine receptor type 2 (CCR2)
  • monocytes
  • macrophages
  • heart injury

Footnotes

  • ↵* Contributed equally to this work.

  • Published online May 22, 2020.

  • © 2021 by the Society of Nuclear Medicine and Molecular Imaging.
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Journal of Nuclear Medicine: 62 (1)
Journal of Nuclear Medicine
Vol. 62, Issue 1
January 1, 2021
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Targeted PET Imaging of Chemokine Receptor 2–Positive Monocytes and Macrophages in the Injured Heart
Gyu Seong Heo, Geetika Bajpai, Wenjun Li, Hannah P. Luehmann, Deborah H. Sultan, Hao Dun, Florian Leuschner, Steven L. Brody, Robert J. Gropler, Daniel Kreisel, Kory J. Lavine, Yongjian Liu
Journal of Nuclear Medicine Jan 2021, 62 (1) 111-114; DOI: 10.2967/jnumed.120.244673

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Targeted PET Imaging of Chemokine Receptor 2–Positive Monocytes and Macrophages in the Injured Heart
Gyu Seong Heo, Geetika Bajpai, Wenjun Li, Hannah P. Luehmann, Deborah H. Sultan, Hao Dun, Florian Leuschner, Steven L. Brody, Robert J. Gropler, Daniel Kreisel, Kory J. Lavine, Yongjian Liu
Journal of Nuclear Medicine Jan 2021, 62 (1) 111-114; DOI: 10.2967/jnumed.120.244673
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Keywords

  • PET
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  • monocytes
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