title: 2-deoxy-2-[18F]fluoro-D-mannose positron emission tomography imaging in atherosclerosis.
abstract: Progressive inflammation in atherosclerotic plaques is associated with increasing risk of plaque rupture. Molecular imaging of activated macrophages with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) has been proposed for identification of patients at higher risk for acute vascular events. Because mannose is an isomer of glucose that is taken up by macrophages through glucose transporters and because mannose receptors are expressed on a subset of the macrophage population in high-risk plaques, we applied (18)F-labeled mannose (2-deoxy-2-[(18)F]fluoro-D-mannose, [(18)F]FDM) for targeting of plaque inflammation. Here, we describe comparable uptake of [(18)F]FDM and [(18)F]FDG in atherosclerotic lesions in a rabbit model; [(18)F]FDM uptake was proportional to the plaque macrophage population. Our FDM competition studies in cultured cells with 2-deoxy-2-[(14)C]carbon-D-glucose ([(14)C]2DG) support at least 35% higher [(18)F]FDM uptake by macrophages in cell experiments. We also demonstrate that FDM restricts binding of anti-mannose receptor antibody to macrophages by approximately 35% and that mannose receptor targeting may provide an additional avenue for imaging of plaque inflammation.
authors.affiliation: 1] Kurume University School of Medicine, Kurume, Japan. [2].
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tahara
authors.affiliation: 1] [2].
authors.forename: Jogeshwar
authors.initials: J
authors.lastname: Mukherjee
authors.affiliation: 1] Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. [3].
authors.forename: Hans J
authors.initials: HJ
authors.lastname: de Haas
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Artiom D
authors.initials: AD
authors.lastname: Petrov
authors.affiliation: Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Tawakol
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Nezam
authors.initials: N
authors.lastname: Haider
authors.affiliation: Kurume University School of Medicine, Kurume, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Tahara
authors.forename: Cristian C
authors.initials: CC
authors.lastname: Constantinescu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Hendrikus H
authors.initials: HH
authors.lastname: Boersma
authors.affiliation: Kurume University School of Medicine, Kurume, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Imaizumi
authors.affiliation: CVPath Institute, Gaithersburg, Maryland, USA.
authors.forename: Masataka
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Aloke
authors.initials: A
authors.lastname: Finn
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Zahi
authors.initials: Z
authors.lastname: Fayad
authors.affiliation: CVPath Institute, Gaithersburg, Maryland, USA.
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
authors.affiliation: 1] Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), Madrid, Spain.
authors.forename: Lisardo
authors.initials: L
authors.lastname: Bosca
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Jagat
authors.initials: J
authors.lastname: Narula
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis* / Q000473:pathology; D001345:Autoradiography; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000648:ultrastructure*; D049268:Positron-Emission Tomography / Q000379:methods*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D012210:Rhamnose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014057:Tomography, X-Ray Computed
chemical_list: D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; C017190:2-deoxy-2-fluoromannose; D012210:Rhamnose