In vivo imaging of activated endothelium using an anti-VCAM-1 magnetooptical probe.
It has been suggested that vascular cell adhesion molecule-1 (VCAM-1) could serve as an early marker for inflammation of the endothelium. The ability to noninvasively image VCAM-1 could thus be a useful tool to diagnose a number of inflammatory diseases at early stages. Here we demonstrate that magnetooptical nanoparticles conjugated to anti-VCAM-1 antibodies can be used to specifically detect VCAM-1 expression on endothelial cells in culture and in vivo. Elevated VCAM-1 expression was detected on cultured murine heart endothelial cells by both fluorescence and magnetic resonance, while only basal expression levels were detected on murine dermal endothelial cells. Intravital microscopy of a murine inflammatory model injected with the VCAM-1 targeted nanoparticles revealed specific labeling of the activated endothelium, with labeling kinetics yielding a maximum vessel wall signal 6 h after injection. In contrast, nontargeted nanoparticles did not exhibit any specific labeling of the endothelium. These studies suggest that the developed nanoparticle would be useful for MR and optical detection of activated endothelium.
Tsourkas
Andrew
A
Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129-2060, USA.
Shinde-Patil
Vivek R
VR
Kelly
Kimberly A
KA
Patel
Pratik
P
Wolley
Allison
A
Allport
Jennifer R
JR
Weissleder
Ralph
R
D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000276:immunology*; D002478:Cells, Cultured; D004727:Endothelium / Q000378:metabolism*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008280:Magnetics; D051379:Mice; D018613:Microscopy, Confocal; D015394:Molecular Structure; D055095:Optics and Photonics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1