Magnetic resonance imaging of inflammation with a specific selectin-targeted contrast agent.

Abstract

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(x), 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 lipopolysaccharide. 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.

• Authors: Sébastien Boutry, Carmen Burtea, Sophie Laurent, Gérard Toubeau, Luce Vander Elst, Robert N Muller
• Journal: Magnetic resonance in medicine (Magn Reson Med) Vol. 53 Issue 4 Pg. 800-7 (Apr 2005) ISSN: 0740-3194 [Print] United States
• PMID: 15799062 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2005 Wiley-Liss, Inc.

Chemical References

• Contrast Media
• E-Selectin
• Gadolinium DTPA

Topics

• Animals
• Contrast Media (chemistry, pharmacokinetics)
• E-Selectin (chemistry)
• Gadolinium DTPA (analogs & derivatives, chemistry, pharmacokinetics)
• Hepatitis (metabolism, pathology)
• Magnetic Resonance Imaging
• Male
• Mice
• Mice, Inbred BALB C
• Tissue Distribution