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

Magn Reson Med. 2000 Sep;44(3):433-9. doi: 10.1002/1522-2594(200009)44:3<433::aid-mrm14>;2-9.


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

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / metabolism
  • Antibody Specificity
  • Biotinylation
  • Contrast Media / administration & dosage*
  • Contrast Media / chemistry
  • Cornea / blood supply
  • Cornea / pathology
  • Corneal Neovascularization / chemically induced
  • Corneal Neovascularization / diagnosis*
  • Corneal Neovascularization / metabolism
  • Corneal Neovascularization / pathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Fibroblast Growth Factor 2
  • Fluorocarbons* / administration & dosage
  • Gadolinium / administration & dosage
  • Image Enhancement / methods*
  • Immunohistochemistry
  • Injections, Intravenous
  • Magnetic Resonance Angiography / methods*
  • Microspheres
  • Neovascularization, Pathologic / chemically induced
  • Neovascularization, Pathologic / diagnosis
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Rabbits
  • Receptors, Vitronectin / immunology
  • Receptors, Vitronectin / metabolism*
  • Thrombomodulin / metabolism


  • Antibodies, Monoclonal
  • Contrast Media
  • Fluorocarbons
  • Receptors, Vitronectin
  • Thrombomodulin
  • Fibroblast Growth Factor 2
  • Gadolinium