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

Journal article

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 μm) 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 μm. 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 (R2 = 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.

Authors: von zur Muhlen, C; Peter, K; Ali, ZA; Schneider, JE; McAteer, MA

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Karger Publishers
• Journal: Journal of Vascular Research
• Volume: 46
• Issue: 1
• Pages: 6-14
• Publication date: 2009-05-31
• Acceptance date: 2008-01-19
• DOI: 10.1159/000135660
• EISSN: 1423-0135
• ISSN: 1018-1172
• Language: English
• Keywords: molecular imaging; magnetic resonance imaging; atherosclerosis; thrombosis; platelets