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.
METHODS AND 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.

Links

Publisher Full Text

Authors

Burtea C, Ballet S, Laurent S, Rousseaux O, Dencausse A, Gonzalez W, Port M, Corot C, Vander Elst L, Muller RN

Institution

Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, Mendeleev Building, B-7000 Mons, Belgium.

Source

Arteriosclerosis, thrombosis, and vascular biology 32:6 2012 Jun pg e36-48

MeSH

Animals
Aorta, Abdominal
Aortic Diseases
Apolipoproteins E
Apoptosis
Atherosclerosis
Contrast Media
Dextrans
Disease Models, Animal
Female
Human Umbilical Vein Endothelial Cells
Humans
Injections, Intravenous
Jurkat Cells
Macrophages
Magnetic Resonance Imaging
Magnetite Nanoparticles
Mice
Mice, Knockout
Necrosis
Peptides
Plaque, Atherosclerotic
Predictive Value of Tests
Protein Binding
Tissue Distribution
Vascular Cell Adhesion Molecule-1

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22516067