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 anew, target-specific MR contra st 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 sires for detectio n by MRI. ACPLs targeted to intercellular adhesion molecule-1 (ICAM-1), an endothelial leukocyte receptor upregulated on cerebral microvasculature dur ing EAE, were administered to diseased mice. Fluorescence microscopy confir med that fluorescently-tagged ACPLs were localized to central nervous syste m (CNS) microvasculature in a pattern consistent with ICAM-1 upregulation d escribed 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 A CPLs can be used as MRI contrast agents to visualize specific:molecules exp ressed on vascular endothelium during disease. (C) 2000 Elsevier Science B. V. All rights reserved.