Vascular in vivo MRI for the detection of arterial thrombosis by targeting activated platelets - new imaging agents for MRI approaches

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Activated platelets are early indicators of imminent rupture of the fibrous cap in unstable atherosclerotic plaques. Therefore, non-invasive MRI of activated platelets would be of great clinical interest. In previous studies we evaluated microparticles of iron oxide (MPIO) coated with a single-chain antibody targeting ligand-induced binding sites (LIBS) on activated glycoprotein IIb/IIIa to image carotid artery thrombosis in mice. Even though these studies allowed successful imaging, limitations of this technique are models of minor platelet aggregation and high shear stress on the platelet surface, which do not result in sufficient binding of such microparticles. Furthermore, toxicity of the used particles prevents application in humans. We therefore aim to conjugate nanoparticle based imaging agents (size 10-100 nm) to LIBS-specific antibodies and apply these in a model of minor vascular platelet adhesion (femoral wire injury model in mice) and wall adherent arterial thrombosis (carotid artery injury model). The nanoparticle-based imaging agents that will be investigated for possible human applications include superparamagetic iron oxide nanoparticles, gadolinium dendrimers, and liposome encapsulated fluorinated markers. Using this approach, we aim to continue the development of a platelet-based contrast agent that can be directly transferred into human applications in future projects. The ultimate aim of the project is to enable the clinician to image rupture-prone atherosclerotic plaques before they cause myocardial infarction or stroke.