Magnetic resonance contrast enhancement of neovasculature with alpha(v)beta(3)-targeted nanoparticles

Site-directed contrast enhancement of angiogenic vessels in vivo was demons trated using antibody targeting of an MRI contrast agent to the alpha(nu)be ta(3) integrin, a molecular marker characteristic of angiogenic endothelium . The agent was tested in a rabbit corneal micropocket model, in which neov asculature is induced in the cornea using basic fibroblast growth factor. T he targeted contrast agent consists of Gd-perfluorocarbon nanoparticles lin ked to alpha(nu)beta(3) integrin antibody DM101. The animal group receiving the targeted contrast agent displayed a 25% increase in the average MR sig nal intensity after 90 min. Control groups in which the nanoparticles are e ither used alone, linked to an isotype-matched antibody, or linked to DM101 and administered following receptor blocking did not display MR contrast e nhancement at similar dose levels. These findings indicate that the antibod y-targeted agent enhances MR signal intensity in the capillary bed in a cor neal micropocket model of angiogenesis, and is selectively retained within the angiogenic region via specific interaction with the alpha(nu)beta(3) ep itope. (C) 2000 Wiley-Liss, Inc.