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2006-01-01 - Article/Dans un journal avec peer-review - Anglais - 8 page(s)

Boutry Sébastien , Laurent Sophie , Vander Elst Luce , Muller Robert , "Specific E-selectin targeting with a superparamagnetic MRI contrast agent" in Contrast Media & Molecular Imaging, 1, 1, 15-22

  • Edition : John Wiley & Sons, Inc, Chichester (United Kingdom)
  • Codes CREF : Résonance magnétique nucléaire (biophysique) (DI131B), Chimie organique (DI1313), Imagerie médicale, radiologie, tomographie (DI3243), Chimie inorganique (DI1312)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108)
Texte intégral :

Abstract(s) :

(Anglais) Targeting of the endothelial inflammatory adhesion molecule E-selectin by magnetic resonance imaging (MRI) was performed with a superparamagnetic contrast agent in the context of in vitro and in vivo models of inflammation. The specific contrast agent was obtained by grafting a synthetic mimetic of sialyl Lewisx (sLex), a natural ligand of E-selectin expressed on leukocytes, on the dextran coating of ultrasmall particles of iron oxide (USPIO). This new contrast agent, called USPIO-g-sLex, was tested, in vitro, on cultured human umbilical vein endothelial cells (HUVECs) stimulated to express inflammatory adhesion molecules, and in vivo, on a mouse model of hepatitis. In vitro, HUVECs were stimulated with the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-) and were then incubated with USPIO-g-sLex or ungrafted USPIO. In vivo, hepatitis was induced on NMRI mice by injection of concanavalin A (Con A). USPIO-g-sLex and ungrafted USPIO were injected intravenously. In vitro results showed an extensive retention of USPIO-g-sLex on TNF- stimulated HUVECs. Image intensity and R2 measurements performed on T2-weighted MR images demonstrated a significantly higher binding of USPIO-g-sLex on stimulated HUVECs. In vivo, USPIO are known to pass through the fenestrae of the liver and to be captured by Kupffer cells, inducing a loss of signal intensity on T2-weighted MR images. Unexpectedly, when injected to Con A-treated mice, USPIO-g-sLex induced a significantly lower attenuation of liver signal intensity than USPIO or USPIO-g-sLex injected to healthy mice, or USPIO injected to Con A-treated mice, suggesting that the specific contrast media is retained extracellularly by an interaction with E-selectin overexpressed on the vascular endothelium. Both in vitro and in vivo results therefore indicate that USPIO-g-sLex is recognizing endothelial E-selectin. USPIO-g-sLex is thus well suited for the MRI diagnosis of inflammation and for the in vitro evaluation of endothelial cells activation.

Identifiants :
  • DOI : 10.1002/cmmi.87
  • PMID : 17193596