Polyglucose nanoparticles with renal elimination and macrophage avidity facilitate PET imaging in ischaemic heart disease

Edmund J. Keliher, Yu-Xiang Ye, Gregory R. Wojtkiewicz, Aaron D. Aguirre, Benoit Tricot, Max L. Senders, Hannah Groenen, Francois Fay, Carlos Perez-Medina, Claudia Calcagno, Giuseppe Carlucci, Thomas Reiner, Yuan Sun, Gabriel Courties, Yoshiko Iwamoto, Hye-Yeong Kim, Cuihua Wang, John W. Chen, Filip K. Swirski, Hsiao-Ying Wey, Jacob Hooker, Zahi A. Fayad, Willem J. M. Mulder, Ralph Weissleder () and Matthias Nahrendorf ()
Additional contact information
Edmund J. Keliher: Massachusetts General Hospital and Harvard Medical School
Yu-Xiang Ye: Massachusetts General Hospital and Harvard Medical School
Gregory R. Wojtkiewicz: Massachusetts General Hospital and Harvard Medical School
Aaron D. Aguirre: Massachusetts General Hospital and Harvard Medical School
Benoit Tricot: Massachusetts General Hospital and Harvard Medical School
Max L. Senders: Icahn School of Medicine at Mount Sinai
Hannah Groenen: Icahn School of Medicine at Mount Sinai
Francois Fay: Icahn School of Medicine at Mount Sinai
Carlos Perez-Medina: Icahn School of Medicine at Mount Sinai
Claudia Calcagno: Icahn School of Medicine at Mount Sinai
Giuseppe Carlucci: Memorial Sloan-Kettering Cancer Center
Thomas Reiner: Memorial Sloan-Kettering Cancer Center
Yuan Sun: Massachusetts General Hospital and Harvard Medical School
Gabriel Courties: Massachusetts General Hospital and Harvard Medical School
Yoshiko Iwamoto: Massachusetts General Hospital and Harvard Medical School
Hye-Yeong Kim: Massachusetts General Hospital and Harvard Medical School
Cuihua Wang: Massachusetts General Hospital and Harvard Medical School
John W. Chen: Massachusetts General Hospital and Harvard Medical School
Filip K. Swirski: Massachusetts General Hospital and Harvard Medical School
Hsiao-Ying Wey: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Jacob Hooker: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Zahi A. Fayad: Icahn School of Medicine at Mount Sinai
Willem J. M. Mulder: Icahn School of Medicine at Mount Sinai
Ralph Weissleder: Massachusetts General Hospital and Harvard Medical School
Matthias Nahrendorf: Massachusetts General Hospital and Harvard Medical School

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract Tissue macrophage numbers vary during health versus disease. Abundant inflammatory macrophages destruct tissues, leading to atherosclerosis, myocardial infarction and heart failure. Emerging therapeutic options create interest in monitoring macrophages in patients. Here we describe positron emission tomography (PET) imaging with 18F-Macroflor, a modified polyglucose nanoparticle with high avidity for macrophages. Due to its small size, Macroflor is excreted renally, a prerequisite for imaging with the isotope flourine-18. The particle’s short blood half-life, measured in three species, including a primate, enables macrophage imaging in inflamed cardiovascular tissues. Macroflor enriches in cardiac and plaque macrophages, thereby increasing PET signal in murine infarcts and both mouse and rabbit atherosclerotic plaques. In PET/magnetic resonance imaging (MRI) experiments, Macroflor PET imaging detects changes in macrophage population size while molecular MRI reports on increasing or resolving inflammation. These data suggest that Macroflor PET/MRI could be a clinical tool to non-invasively monitor macrophage biology.

Date: 2017
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DOI: 10.1038/ncomms14064

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