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 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.
Sipkins
D A
DA
Department of Radiology, Stanford University School of Medicine, Lucas MRS Research Center, Stanford, CA 94305-5429, USA.
Gijbels
K
K
Tropper
F D
FD
Bednarski
M
M
Li
K C
KC
Steinman
L
L
D000818:Animals; D000911:Antibodies, Monoclonal; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000378:metabolism*; D004337:Drug Carriers; D004660:Encephalitis / Q000175:diagnosis* / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005682:Gadolinium / Q000008:administration & dosage; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008081:Liposomes; D008279:Magnetic Resonance Imaging; D051379:Mice; D008815:Mice, Inbred Strains; D008856:Microscopy, Fluorescence; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D008081:Liposomes; D018799:Intercellular Adhesion Molecule-1; D005682:Gadolinium