title: Development of a magnetic resonance imaging protocol for the characterization of atherosclerotic plaque by using vascular cell adhesion molecule-1 and apoptosis-targeted ultrasmall superparamagnetic iron oxide derivatives.
abstract: OBJECTIVE
  Acute ischemic events are often caused by the disruption of lipid-rich plaques, which are frequently not angiographically visible. Vascular cell adhesion molecule-1 and apoptotic cell-targeted peptides studied during our previous work were conjugated to ultrasmall superparamagnetic iron oxide (USPIO) (USPIO-R832 for vascular cell adhesion molecule-1 targeting; USPIO-R826 for apoptosis targeting) and assessed by magnetic resonance imaging.
  
  
  RESULTS
  Apolipoprotein E knockout mice were injected with 0.1 mmol Fe/kg body weight and were imaged on a 4.7-T Bruker magnetic resonance imaging until 24 hours after contrast agent administration. Aortic samples were then harvested and examined by histochemistry, and the magnetic resonance images and histological micrographs were analyzed with ImageJ software. The plaques enhanced by USPIO-R832 contained macrophages concentrated in the cap and a large necrotic core, whereas USPIO-R826 produced a negative enhancement of plaques rich in macrophages and neutral fats concentrated inside the plaque. Both USPIO derivatives colocalized with their target on histological sections and were able to detect plaques with a vulnerable morphology, but each one is detecting a specific environment.
  
  
  CONCLUSIONS
  Our vascular cell adhesion molecule-1 and apoptotic cell targeted USPIO derivatives seem to be highly promising tools for atherosclerosis imaging contributing to the detection of vulnerable plaques. They are able to attain their target in low doses and as fast as 30 minutes after administration.
authors.affiliation: Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, Mendeleev Building, B-7000 Mons, Belgium.
authors.forename: Carmen
authors.initials: C
authors.lastname: Burtea
authors.forename: Sébastien
authors.initials: S
authors.lastname: Ballet
authors.forename: Sophie
authors.initials: S
authors.lastname: Laurent
authors.forename: Olivier
authors.initials: O
authors.lastname: Rousseaux
authors.forename: Anne
authors.initials: A
authors.lastname: Dencausse
authors.forename: Walter
authors.initials: W
authors.lastname: Gonzalez
authors.forename: Marc
authors.initials: M
authors.lastname: Port
authors.forename: Claire
authors.initials: C
authors.lastname: Corot
authors.forename: Luce
authors.initials: L
authors.lastname: Vander Elst
authors.forename: Robert N
authors.initials: RN
authors.lastname: Muller
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D017209:Apoptosis; D050197:Atherosclerosis / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics; D003911:Dextrans / Q000008:administration & dosage / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007275:Injections, Intravenous; D019169:Jurkat Cells; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000008:administration & dosage; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics; D058226:Plaque, Atherosclerotic / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D011485:Protein Binding; D014018:Tissue Distribution; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010455:Peptides; D019010:Vascular Cell Adhesion Molecule-1; C097921:ferumoxtran-10