Activated platelets play a prominent role in multiple diseases, in particular arterial and venous thrombosis, as well as in atherosclerosis and cancer. More recent studies demonstrate further an important role for platelets in generating a permissive microenvironment for tumor growth, and the promotion of invasion and metastasis. To advance the in vivo study of the biological activity of this activated cell type from basic experimental to a clinical focus, new translatable platelet-specific molecular imaging agents are required. Herein, we report the development of a near-infrared fluorescence probe based upon tirofiban, a clinically-approved small molecule glycoprotein IIb/IIIa inhibitor (GPIIb/IIIa). Through in vitro experiments with human platelets, and in vivo in a murine model of deep vein thrombosis, we demonstrate the avidity of the generated probe for activated platelets, thereby enabling rapid in vivo visualization within the vasculature
|