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Platelets can be found on the surface of inflamed and ruptured atherosclerotic plaques. Thus, targeting of activated platelets may allow for molecular imaging of vulnerable atherosclerotic lesions. We here investigated microbubbles (MB) functionalized with the selectin ligand sialyl Lewis a  individually (MB sLea ) or dually with sLe a  and an antibody targeting ligand-induced binding sites of the activated GPIIb/IIIa receptor (MB Dual ). Assessed by  in vitro  flow chamber, targeted MB exhibited increased adhesion to platelets as compared to MB Control . While MB sLea  rolled slowly on the platelets’ surface, MB Dual  enhanced the percentage of firm adhesion.  In vivo , MB were investigated by ultrasound in a model of ferric chloride induced non-occlusive carotid artery thrombosis. MB sLea  and MB Dual  revealed a higher ultrasound mean acoustic intensity than MB Control  (p < 0.05), however MB Dual  demonstrated no additional increase in mean signal intensity as compared to MB sLea . The degree of carotid artery stenosis on histology correlated well with the ultrasound acoustic intensity of targeted MB (p < 0.05). While dual targeting of MB using fast binding carbohydrate polymers and specific antibodies is a promising strategy to support adhesion to activated platelets under arterial shear stress, these advantages seem not readily translatable to  in vivo  models.

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Dual targeting improves capture of ultrasound microbubbles towards activated platelets but yields no additional benefit for imaging of arterial thrombosis