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2005-01-01 - Article/Dans un journal avec peer-review - Anglais - 8 page(s)

Boutry Sébastien , Burtea Carmen , Laurent Sophie , Toubeau Gérard, Vander Elst Luce , Muller Robert , "Magnetic resonance imaging of inflammation with a specific selectin-targeted contrast agent" in Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine, 53, 4, 800-807

  • Edition : Wiley Liss, Inc., New York (NY)
  • Codes CREF : Résonance magnétique nucléaire (biophysique) (DI131B), Sciences biomédicales (DI3200), Pharmacocinétique (DI3431), Chimie organique (DI1313), Imagerie médicale, radiologie, tomographie (DI3243)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108), Histologie (M118)
Texte intégral :

Abstract(s) :

(Anglais) E-selectin-targeted contrast enhancement of blood vessels in inflamed tissues was investigated with a new contrast agent, Gd-DTPA-B(sLe(x))A, which was recently obtained by grafting a synthetic mimetic of sialyl-Lewis ', an E-selectin ligand, onto Gd-DTPA. The pharmacokinetics, biodistribution, and potential to image inflammation by MRI of this E-selectin-targeted contrast agent were evaluated. The inhibition (by 15-34%) produced by Gd-DTPA-B(sLe(x))A on Sialyl Le(x)-PAA-biotin binding to E-selectin confirmed the specific interaction of the new contrast agent with this adhesion molecule. Gd-DTPA-B(sLe(x))A was tested at a dose of 0.1 mmol/kg b.w. on mice and rats in a fulminant hepatitis model induced by the co-administration of D-galactosamine and E. coli lipopolysaccha ride. A significant and prolonged contrast enhancement between blood vessels and liver parenchyma was obtained in pathological conditions, which attests to the specificity of the agent for E-selectin. The prolonged vascular residence (48.9 min in hepatitis vs. 29.8 min in healthy animals), as evidenced by the pharmacokinetic characterization, suggests that Gd-DTPA-B(sLe(x))A interacts with the specific receptors expressed during inflammation. The biodistribution of the compound indicates its retention in inflamed liver by both specific mechanisms and nonspecific accumulation due to the necrotic lesions. The same mechanisms are invoked to account for its retention in the spleen.

Identifiants :
  • DOI : 10.1002/mrm.20403
  • PMID : 15799062

Mots-clés :
  • (Anglais) E-selectin
  • (Anglais) inflammation
  • (Anglais) molecular imaging
  • (Anglais) magnetic resonance imaging
  • (Anglais) MRI contrast agents