Platelets are the key to thrombus formation in atherothrombosis and play a major role in plaque rupture. Non-invasive imaging of activated platelets would be of great clinical interest. Here, we evaluate the ability of a magnetic resonance imaging (MRI) contrast agent consisting of microparticles of iron oxide (MPIO) and a single-chain antibody targeting ligand-induced binding sites (LIBS) on activated GPIIb/IIIa to image carotid artery thrombosis and. Anti-LIBS or control antibody were conjugated to 1μm-sized MPIOs (LIBS-MPIO/control-MPIO). Non-occlusive wall-adherent thrombi were induced in BL/6 mice using 6% ferric chloride. MRI (at 9.4 Tesla) of the carotid artery was performed once before (figure
, A) and repeatedly in 12min long sequences after LIBS-MPIO/control-MPIO injection. After 36min, a significant signal void, which is the typical effect of iron oxide-based contrast agents, was observed with LIBS-MPIO (figure
, B), but not control-MPIO (P<0.01) and corresponded to LIBS-MPIO binding as confirmed by histology. After thrombolysis, in LIBS-MPIO injected mice the signal void subsided, indicating successful thrombolysis (figure
, C). On histology, MPIO-content of thrombus, as well as thrombus size, correlated significantly with LIBS-MPIO-induced signal void (both P<0.01). LIBS-MPIO allows in vivo MRI of activated platelets with excellent contrast properties and monitoring of thrombolytic therapy. This approach represents a novel non-invasive technique allowing rapid detection and quantification of platelet-containing thrombi, such as found on the surface of ruptured atherosclerotic plaques.
Application of Serial In Vivo Magnetic Resonance Imaging to Evaluate the Efficacy of Endothelin Receptor Antagonist SB 217242 in the Rat Carotid Artery Model of Neointima Formation