Targeting of ICAM-1 on vascular endothelium under static and shear stress conditions using a liposomal Gd-based MRI contrast agent

L.E.M. Paulis, I. Jacobs, N.M. van den Akker, T. Geelen, D.G. Molin, L.W.E. Starmans, K. Nicolay, G.J. Strijkers

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    Abstract

    Background
    The upregulation of intercellular adhesion molecule-1 (ICAM-1) on the endothelium of blood vessels in response to pro-inflammatory stimuli is of major importance for the regulation of local inflammation in cardiovascular diseases such as atherosclerosis, myocardial infarction and stroke. In vivo molecular imaging of ICAM-1 will improve diagnosis and follow-up of patients by non-invasive monitoring of the progression of inflammation.

    Results
    A paramagnetic liposomal contrast agent functionalized with anti-ICAM-1 antibodies for multimodal magnetic resonance imaging (MRI) and fluorescence imaging of endothelial ICAM-1 expression is presented. The ICAM-1-targeted liposomes were extensively characterized in terms of size, morphology, relaxivity and the ability for binding to ICAM-1-expressing endothelial cells in vitro. ICAM-1-targeted liposomes exhibited strong binding to endothelial cells that depended on both the ICAM-1 expression level and the concentration of liposomes. The liposomes had a high longitudinal and transversal relaxivity, which enabled differentiation between basal and upregulated levels of ICAM-1 expression by MRI. The liposome affinity for ICAM-1 was preserved in the competing presence of leukocytes and under physiological flow conditions.

    Conclusion
    This liposomal contrast agent displays great potential for in vivo MRI of inflammation-related ICAM-1 expression.
    Original languageEnglish
    Pages (from-to)1-12
    Number of pages12
    JournalJournal of Nanobiotechnology
    Volume10
    DOIs
    Publication statusPublished - 20 Jun 2012

    Keywords

    • Molecular MRI
    • Liposome
    • ICAM-1
    • Endothelium
    • Leukocyte
    • Shear stress

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