Visualization of activated platelets by targeted magnetic resonance imaging utilizing conformation-specific antibodies against glycoprotein IIb/IIIa

J Vasc Res. 2009;46(1):6-14. doi: 10.1159/000135660. Epub 2008 May 31.

Abstract

Ruptured atherosclerotic plaques, lined with activated platelets, constitute an attractive target for magnetic resonance imaging (MRI). This study evaluated whether microparticles of iron oxide (MPIO) targeting ligand-induced binding sites (LIBS) on the activated conformation of glycoprotein IIb/IIIa could be used to image platelets. MPIO (size: 1 microm) were conjugated to anti-LIBS or control single-chain antibody. Following guidewire injury to mouse femoral artery, platelet adhesion was present after 24 h. Mice were perfused with anti-LIBS-MPIO (or control MPIO) via the left ventricle and 11.7-tesla MRI was performed on femoral arteries ex vivo. A 3D gradient echo sequence attained an isotropic resolution of 25 microm. MPIO binding, quantified by MRI, was 4-fold higher with anti-LIBS-MPIO in comparison to control MPIO (p < 0.01). In histological sections, low signal zones on MRI and MPIO correlated strongly (R(2) = 0.72; p < 0.001), indicating accurate MR quantification. In conclusion, anti-LIBS-MPIO bind to activated platelets in mouse arteries, providing a basis for the use of function-specific single-chain antibody-MPIO conjugates for molecular MRI, and represent the first molecular imaging of a conformational change in a surface receptor. This presents an opportunity to specifically image activated platelets involved in acute atherothrombosis with MRI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies
  • Binding Sites
  • Binding Sites, Antibody
  • Blood Platelets
  • Femoral Artery / injuries
  • Femoral Artery / ultrastructure
  • Ferric Compounds*
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Platelet Activation
  • Platelet Adhesiveness
  • Platelet Glycoprotein GPIIb-IIIa Complex / immunology
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism*
  • Protein Conformation
  • Receptors, Immunologic / metabolism

Substances

  • Antibodies
  • Ferric Compounds
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Receptors, Immunologic
  • ferric oxide