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Specific E-selectin targeting with a superparamagnetic MRI contrast agent.

Sébastien Boutry1, Sophie Laurent, Luce Vander Elst

  • 1Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, B-7000 Mons, Belgium.

Contrast Media & Molecular Imaging
|December 29, 2006
PubMed
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This study developed a novel contrast agent, ultrasmall particles of iron oxide grafted with sialyl Lewis(x) (USPIO-g-sLe(x)), for magnetic resonance imaging (MRI) of inflammation. The agent specifically targets E-selectin on inflamed endothelial cells, showing promise for diagnosing inflammatory conditions.

Area of Science:

  • Biomedical Imaging
  • Nanotechnology
  • Immunology

Background:

  • Inflammation involves endothelial adhesion molecules like E-selectin.
  • Targeting E-selectin is crucial for diagnosing inflammatory diseases.
  • Ultrasmall particles of iron oxide (USPIO) are used as MRI contrast agents.

Purpose of the Study:

  • To develop and evaluate a novel E-selectin-targeted MRI contrast agent.
  • To assess the in vitro and in vivo efficacy of USPIO-g-sLe(x) for detecting inflammation.
  • To investigate the potential of USPIO-g-sLe(x) for diagnosing endothelial activation.

Main Methods:

  • Synthesized USPIO-g-sLe(x) by grafting a sialyl Lewis(x) mimetic onto USPIO.
  • Tested USPIO-g-sLe(x) in vitro on tumor necrosis factor alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells (HUVECs).

Related Experiment Videos

  • Evaluated USPIO-g-sLe(x) in vivo using a concanavalin A (Con A)-induced hepatitis mouse model.

    • Main Results:

    • USPIO-g-sLe(x) showed significant retention on stimulated HUVECs in vitro.
    • T(2)-weighted MRI revealed higher binding of USPIO-g-sLe(x) to activated HUVECs.
    • In vivo, USPIO-g-sLe(x) demonstrated specific retention in inflamed liver vasculature, suggesting E-selectin interaction.

    Conclusions:

    • USPIO-g-sLe(x) effectively targets endothelial E-selectin in both in vitro and in vivo models.
    • This targeted contrast agent is suitable for MRI diagnosis of inflammation.
    • USPIO-g-sLe(x) can be used for in vitro evaluation of endothelial cell activation.