Magnetic resonance contrast enhancement of neovasculature with alpha(v)beta(3)-targeted nanoparticles.
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.
Anderson
S A
SA
Monsanto Company, St. Louis, Missouri, USA.
Rader
R K
RK
Westlin
W F
WF
Null
C
C
Jackson
D
D
Lanza
G M
GM
Wickline
S A
SA
Kotyk
J J
JJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D000918:Antibody Specificity; D019921:Biotinylation; D003287:Contrast Media / Q000008:administration & dosage* / Q000737:chemistry; D003315:Cornea / Q000098:blood supply / Q000473:pathology; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2; D005466:Fluorocarbons / Q000008:administration & dosage; D005682:Gadolinium / Q000008:administration & dosage; D007089:Image Enhancement / Q000379:methods*; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008863:Microspheres; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D019030:Receptors, Vitronectin / Q000276:immunology / Q000378:metabolism*; D018180:Thrombomodulin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D003287:Contrast Media; D005466:Fluorocarbons; D019030:Receptors, Vitronectin; D018180:Thrombomodulin; D016222:Fibroblast Growth Factor 2; D005682:Gadolinium