Abstract
Site-directed contrast enhancement of angiogenic vessels in vivo was demonstrated using antibody targeting of an MRI contrast agent to the alpha(v)beta(3) integrin, a molecular marker characteristic of angiogenic endothelium. The agent was tested in a rabbit corneal micropocket model, in which neovasculature is induced in the cornea using basic fibroblast growth factor. The targeted contrast agent consists of Gd-perfluorocarbon nanoparticles linked to alpha(v)beta(3) integrin antibody DM101. The animal group receiving the targeted contrast agent displayed a 25% increase in the average MR signal intensity after 90 min. Control groups in which the nanoparticles are either used alone, linked to an isotype-matched antibody, or linked to DM101 and administered following receptor blocking did not display MR contrast enhancement at similar dose levels. These findings indicate that the antibody-targeted agent enhances MR signal intensity in the capillary bed in a corneal micropocket model of angiogenesis, and is selectively retained within the angiogenic region via specific interaction with the alpha(v)beta(3) epitope.
MeSH terms
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Animals
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Antibodies, Monoclonal / chemistry
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Antibodies, Monoclonal / metabolism
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Antibody Specificity
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Biotinylation
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Contrast Media / administration & dosage*
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Contrast Media / chemistry
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Cornea / blood supply
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Cornea / pathology
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Corneal Neovascularization / chemically induced
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Corneal Neovascularization / diagnosis*
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Corneal Neovascularization / metabolism
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Corneal Neovascularization / pathology
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Fibroblast Growth Factor 2
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Fluorocarbons* / administration & dosage
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Gadolinium / administration & dosage
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Image Enhancement / methods*
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Immunohistochemistry
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Injections, Intravenous
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Magnetic Resonance Angiography / methods*
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Microspheres
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Neovascularization, Pathologic / chemically induced
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Neovascularization, Pathologic / diagnosis
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Neovascularization, Pathologic / metabolism
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Neovascularization, Pathologic / pathology
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Rabbits
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Receptors, Vitronectin / immunology
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Receptors, Vitronectin / metabolism*
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Thrombomodulin / metabolism
Substances
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Antibodies, Monoclonal
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Contrast Media
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Fluorocarbons
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Receptors, Vitronectin
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Thrombomodulin
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Fibroblast Growth Factor 2
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Gadolinium