title: Visualization of vascular inflammation in the atherosclerotic mouse by ultrasmall superparamagnetic iron oxide vascular cell adhesion molecule-1-specific nanoparticles.
abstract: OBJECTIVE
  Noninvasive imaging of atherosclerosis remains challenging in clinical applications. Here, we applied noninvasive molecular imaging to detect vascular cell adhesion molecule-1 in early and advanced atherosclerotic lesions of apolipoprotein E-deficient mice.
  
  
  RESULTS
  Ultrasmall superparamagnetic iron oxide particles functionalized with (P03011) or without (P3007) vascular cell adhesion molecule-1-binding peptide were visualized by ultra high-field (17.6 T) magnetic resonance. Injection of P03011 resulted in a marked signal loss in the aortic root of apolipoprotein E-deficient mice fed a Western diet for 8 and 26 weeks in vivo and ex vivo, compared with preinjection measurements, P3007-injected mice, and P03011- or P3007-injected age-matched C57BL/6 controls. Histological analyses revealed iron accumulations in the intima, in colocalization with vascular cell adhesion molecule-1-expressing macrophages and endothelial cells. Coherent anti-Stokes Raman scattering microscopy demonstrated iron signals in the intima and media of the aortic root in the P03011-injected but not untreated apolipoprotein E-deficient mice, localized to macrophages, luminal endothelial-like cells, and medial regions containing smooth muscle cells. Electron microscopy confirmed iron particles enclosed in endothelial cells and in the vicinity of smooth muscle cells.
  
  
  CONCLUSIONS
  Using a combination of innovative imaging modalities, in this study, we demonstrate the feasibility of applying P03011 as a contrast agent for imaging of atherosclerosis.
authors.affiliation: Experimentelle Physik V, Universität Würzburg, Würzburg, Germany.
authors.forename: Marta
authors.initials: M
authors.lastname: Michalska
authors.forename: Lina
authors.initials: L
authors.lastname: Machtoub
authors.forename: Helga D
authors.initials: HD
authors.lastname: Manthey
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bauer
authors.forename: Volker
authors.initials: V
authors.lastname: Herold
authors.forename: Georg
authors.initials: G
authors.lastname: Krohne
authors.forename: Gunthard
authors.initials: G
authors.lastname: Lykowsky
authors.forename: Markus
authors.initials: M
authors.lastname: Hildenbrand
authors.forename: Thomas
authors.initials: T
authors.lastname: Kampf
authors.forename: Peter
authors.initials: P
authors.lastname: Jakob
authors.forename: Alma
authors.initials: A
authors.lastname: Zernecke
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Bauer
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005290:Ferric Compounds / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D013059:Spectrum Analysis, Raman; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D014657:Vasculitis / Q000378:metabolism* / Q000473:pathology*
chemical_list: D001057:Apolipoproteins E; D005290:Ferric Compounds; D019010:Vascular Cell Adhesion Molecule-1; C000499:ferric oxide