title: Novel PET Imaging of Atherosclerosis with 68Ga-Labeled NOTA-Neomannosylated Human Serum Albumin.
abstract: Activated macrophages take up18F-FDG via glucose transporters, so this compound is useful for atherosclerosis imaging by PET. However,18F-FDG application is limited for imaging of the heart and brain, in which glucose uptake is high, and in patients with aberrant glucose metabolism. The aims of this study were to confirm that mannosylated human serum albumin (MSA) specifically binds to the mannose receptor (MR) on macrophages and to test the feasibility of68Ga-labeled NOTA-MSA for PET imaging of atherosclerotic plaques.
  
  
  METHODS
  The peritoneal macrophages of C57/B6 mice were collected, incubated with rhodamine B isothiocyanate-MSA (10 μg/mL), and evaluated by confocal microscopy and flow cytometry. The same evaluations were performed after preincubation of the macrophages with anti-CD206 MR blocking antibodies. NOTA-MSA was synthesized by conjugating 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid to MSA, followed by labeling with68Ga. Rabbits with atherosclerotic aorta induced by a 3-mo cholesterol diet and chronic inflammation underwent consecutive PET/CT with18F-FDG and68Ga-NOTA-MSA at 2-d intervals.
  
  
  RESULTS
  The binding of MSA to MR and its dose-dependent reduction by preincubation with anti-CD206 MR blocking antibody were confirmed. Rhodamine B isothiocyanate and fluorescein isothiocyanate fluorescence colocalized at the atherosclerotic plaque. The68Ga-NOTA-MSA SUVs of the atherosclerotic aorta were significantly higher than those of the healthy arteries and inferior vena cava and were comparable to those obtained with18F-FDG.
  
  
  CONCLUSIONS
  These findings suggest that MR-specific68Ga-NOTA-MSA is effective for detecting atherosclerosis in the aorta and is a promising radiopharmaceutical for imaging atherosclerosis because of the presence of M2 macrophages in atherosclerotic plaques.
authors.affiliation: Cardiovascular Center, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Eung Ju
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Nuclear Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Sungeun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Cardiovascular Center, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea mdhsseo@korea.ac.kr jmjng@snu.ac.kr.|Korea University-Korea Institute of Science and Technology (KU-KIST) Graduate School of Converging Science and Technology, Seoul, South Korea.
authors.forename: Hong Seog
authors.initials: HS
authors.lastname: Seo
authors.affiliation: Cardiovascular Center, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Yong Jik
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Nuclear Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Jae Seon
authors.initials: JS
authors.lastname: Eo
authors.affiliation: Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, South Korea mdhsseo@korea.ac.kr jmjng@snu.ac.kr.
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.affiliation: Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Boeun
authors.initials: B
authors.lastname: Lee
authors.affiliation: Research Institute of Skin Imaging, Korea University College of Medicine, Seoul, South Korea; and.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Molecular Medicine, Ewha Womans University School of Medicine, Seoul, South Korea.
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Park
authors.affiliation: Department of Molecular Medicine, Ewha Womans University School of Medicine, Seoul, South Korea.
authors.forename: Myeongsook
authors.initials: M
authors.lastname: Jeong
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002478:Cells, Cultured; D005240:Feasibility Studies; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics*; D006573:Heterocyclic Compounds, 1-Ring; D006801:Humans; D007553:Isotope Labeling; D037181:Lectins, C-Type / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008358:Mannose / Q000493:pharmacokinetics*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012709:Serum Albumin / Q000493:pharmacokinetics
chemical_list: D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D012709:Serum Albumin; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D008358:Mannose
keywords: atherosclerosis; inflammation; mannose receptor; positron emission tomography