Open Access Research

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

Leonie EM Paulis1, Igor Jacobs1, Nynke M van den Akker2, Tessa Geelen1, Daniel G Molin3, Lucas WE Starmans1, Klaas Nicolay1 and Gustav J Strijkers1*

Author Affiliations

1 Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB, Eindhoven, the Netherlands

2 Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD, Maastricht, the Netherlands

3 Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD, Maastricht, the Netherlands

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Journal of Nanobiotechnology 2012, 10:25 doi:10.1186/1477-3155-10-25

Published: 20 June 2012

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.

Keywords:
Molecular MRI; Liposome; ICAM-1; Endothelium; Leukocyte; Shear stress