Open AccessSpecific E‐selectin targeting with a superparamagnetic MRI contrast agent
Author(s) -
Boutry Sébastien,
Laurent Sophie,
Elst Luce Vander,
Muller Robert N.
Publication year - 2006
Publication title -
contrast media & molecular imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.714
H-Index - 50
eISSN - 1555-4317
pISSN - 1555-4309
DOI - 10.1002/cmmi.87
Subject(s) - in vivo , in vitro , umbilical vein , mri contrast agent , e selectin , chemistry , cell adhesion molecule , context (archaeology) , tumor necrosis factor alpha , pathology , microbiology and biotechnology , medicine , immunology , adhesion , cell adhesion , biochemistry , biology , paleontology , organic chemistry
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 Lewis x (sLe x ), 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‐sLe x , 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‐ α ) and were then incubated with USPIO‐g‐sLe x or ungrafted USPIO. In vivo , hepatitis was induced on NMRI mice by injection of concanavalin A (Con A). USPIO‐g‐sLe x and ungrafted USPIO were injected intravenously. In vitro results showed an extensive retention of USPIO‐g‐sLe x on TNF‐ α stimulated HUVECs. Image intensity and R 2 measurements performed on T 2 ‐weighted MR images demonstrated a significantly higher binding of USPIO‐g‐sLe x 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 T 2 ‐weighted MR images. Unexpectedly, when injected to Con A‐treated mice, USPIO‐g‐sLe x induced a significantly lower attenuation of liver signal intensity than USPIO or USPIO‐g‐sLe x 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‐sLe x is recognizing endothelial E‐selectin. USPIO‐g‐sLe x is thus well suited for the MRI diagnosis of inflammation and for the in vitro evaluation of endothelial cells activation. Copyright © 2006 John Wiley & Sons, Ltd.