title: Polyglucose nanoparticles with renal elimination and macrophage avidity facilitate PET imaging in ischaemic heart disease.
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 with18F-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.
authors.affiliation: Center for Systems Biology and Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Keliher
authors.affiliation: Center for Systems Biology and Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Ye
authors.affiliation: Center for Systems Biology and Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Wojtkiewicz
authors.affiliation: Center for Systems Biology and Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Aguirre
authors.affiliation: Center for Systems Biology and Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
authors.forename: Benoit
authors.initials: B
authors.lastname: Tricot
authors.affiliation: Translational and Molecular Imaging Institute and Department of Radiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.|Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Max L
authors.initials: ML
authors.lastname: Senders
authors.affiliation: Translational and Molecular Imaging Institute and Department of Radiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Groenen
authors.affiliation: Translational and Molecular Imaging Institute and Department of Radiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
authors.forename: Francois
authors.initials: F
authors.lastname: Fay
authors.affiliation: Translational and Molecular Imaging Institute and Department of Radiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Perez-Medina
authors.affiliation: Translational and Molecular Imaging Institute and Department of Radiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Calcagno
authors.affiliation: Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carlucci
authors.affiliation: Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.|Department of Radiology, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiner
authors.affiliation: Center for Systems Biology and Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Center for Systems Biology and Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Courties
authors.affiliation: Center for Systems Biology and Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwamoto
authors.affiliation: Center for Systems Biology and Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
authors.forename: Hye-Yeong
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Center for Systems Biology and Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
authors.forename: Cuihua
authors.initials: C
authors.lastname: Wang
authors.affiliation: Center for Systems Biology and Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Center for Systems Biology and Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Swirski
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Imaging, Massachusetts General Hospital, Harvard Medical School, 149 Thirteenth Street, Charlestown, Massachusetts 02129, USA.
authors.forename: Hsiao-Ying
authors.initials: HY
authors.lastname: Wey
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Imaging, Massachusetts General Hospital, Harvard Medical School, 149 Thirteenth Street, Charlestown, Massachusetts 02129, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Hooker
authors.affiliation: Translational and Molecular Imaging Institute and Department of Radiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.affiliation: Translational and Molecular Imaging Institute and Department of Radiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.|Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Willem J M
authors.initials: WJ
authors.lastname: Mulder
authors.affiliation: Center for Systems Biology and Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Alpert 536, Boston, Massachusetts 02115, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.affiliation: Center for Systems Biology and Department of Imaging, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
mesh_terms: D000818:Animals; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000378:metabolism; D005936:Glucans / Q000737:chemistry / Q000378:metabolism*; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D008264:Macrophages / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000295:instrumentation / Q000379:methods*; D011817:Rabbits; D065667:Renal Elimination
chemical_list: D005462:Fluorine Radioisotopes; D005936:Glucans; C000615276:Fluorine-18