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.
Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis
