ICAM-1 expression in autoimmune encephalitis visualized using magnetic resonance imaging

The expression of leukocyte adhesion molecules in the intact brains of mice with experimental autoimmune encephalitis (EAE) was visualized by Magnetic Resonance Imaging (MRI) through the use of a new, target-specific MR contrast agent. Antibody-conjugated paramagnetic liposomes (ACPLs) were designed...

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Bibliographic Details
Published in:Journal of neuroimmunology 2000-04, Vol.104 (1), p.1-9
Main Authors: Sipkins, Dorothy A, Gijbels, Koenraad, Tropper, François D, Bednarski, Mark, Li, King C.P, Steinman, Lawrence
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal
Autoimmune Diseases - diagnosis
Autoimmune Diseases - metabolism
Drug Carriers
Encephalitis - diagnosis
Encephalitis - metabolism
Endothelium, Vascular - metabolism
Gadolinium - administration & dosage
intercellular adhesion molecule 1
Intercellular Adhesion Molecule-1 - metabolism
Intracellular adhesion molecules (ICAM)
Liposomes
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI)
Mice
Mice, Inbred Strains
Microscopy, Fluorescence
Multiple sclerosis (MS)
Tissue Distribution
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Summary:The expression of leukocyte adhesion molecules in the intact brains of mice with experimental autoimmune encephalitis (EAE) was visualized by Magnetic Resonance Imaging (MRI) through the use of a new, target-specific MR contrast agent. Antibody-conjugated paramagnetic liposomes (ACPLs) were designed to achieve in vivo targeting of molecules expressed on vascular endothelium, while providing sufficient signal enhancement at these sites for detection by MRI. ACPLs targeted to intercellular adhesion molecule-1 (ICAM-1), an endothelial leukocyte receptor upregulated on cerebral microvasculature during EAE, were administered to diseased mice. Fluorescence microscopy confirmed that fluorescently-tagged ACPLs were localized to central nervous system (CNS) microvasculature in a pattern consistent with ICAM-1 upregulation described immunohistochemically. High resolution MRI of mouse brains ex vivo demonstrated that ACPL binding conferred significant enhancement of signal intensity (SI) as compared to control images. These results suggest that ACPLs can be used as MRI contrast agents to visualize specific molecules expressed on vascular endothelium during disease.
ISSN:0165-5728
1872-8421
DOI:10.1016/S0165-5728(99)00248-9