Visualization of activated platelets by targeted magnetic resonance imaging utilizing conformation-specific antibodies against glycoprotein IIb/IIIa.
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.
von zur Muhlen
Constantin
C
Department of Cardiovascular Medicine, University of Oxford, Oxford, UK.
Peter
Karlheinz
K
Ali
Ziad A
ZA
Schneider
Jurgen E
JE
McAteer
Martina A
MA
Neubauer
Stefan
S
Channon
Keith M
KM
Bode
Christoph
C
Choudhury
Robin P
RP
D000818:Animals; D000906:Antibodies; D001665:Binding Sites; D001666:Binding Sites, Antibody; D001792:Blood Platelets; D005263:Femoral Artery / Q000293:injuries / Q000648:ultrastructure; D005290:Ferric Compounds; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology / Q000378:metabolism*; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000378:metabolism
D000906:Antibodies; D005290:Ferric Compounds; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011971:Receptors, Immunologic; C000499:ferric oxide