The development of a multimodal iron-oxide nanoparticle targeting VCAM-1 for in vivo imaging of vulnerable atherosclerotic plaques
House, Adrian Elliot
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It is estimated that, worldwide, over 17 million people die annually as a consequence of cardiovascular diseases (CVDs). As a result of such alarming statistics, modes of early detection have been explored. In recent years, ironoxide nanoparticles combined with radioisotopes have been considered for joint in vivo Positron Emission Tomography (PET)/Magnetic Resonance (MR) imaging. Simultaneous use of these imaging modalities combines the benefits of MR's exceptional tissue contrast and resolution with PET's more sensitive acquisition of molecular data. To take advantage of these properties, a bimodal contrast agent was developed, with iron-oxide serving as the MR contrast moiety and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as a chelator for the positron emitter 64Cu. VCAM-1 targeting peptides were then attached to increase specificity of these nanoparticles to vulnerable in vivo atherosclerotic lesions. The synthesis was verified with Dynamic Light Scattering, Nuclear Magnetic Resonance relaxivity, and endothelial cell culture analysis. Use of the probe was examined in a carotid artery-ligated ApoE CVD mouse model, resulting in significant contrast in MR images coinciding with the injured site.
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