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


CONCLUSIONS
This liposomal contrast agent displays great potential for in vivo MRI of inflammation-related ICAM-1 expression.
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB, Eindhoven, the Netherlands.
Leonie E M
LE
Paulis
Igor
I
Jacobs
Nynke M
NM
van den Akker
Tessa
T
Geelen
Daniel G
DG
Molin
Lucas W E
LW
Starmans
Klaas
K
Nicolay
Gustav J
GJ
Strijkers
D000818:Animals; D002460:Cell Line; D003287:Contrast Media / Q000737:chemistry*; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000378:metabolism*; D005682:Gadolinium / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D057054:Molecular Imaging; D033081:Shear Strength; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D003287:Contrast Media; D007074:Immunoglobulin G; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D005682:Gadolinium