? Recently, the development of targeted contrast agents for molecular imaging has caught the attention of the medical and scientific community. Targeted ultrasound contrast agents, microbubbles which bear adhesion ligands to specific molecular targets expressed in areas such as angiogenesis, inflammation, or thrombus have the potential to make a significant impact in the detection, assessment, and localization of pathologies otherwise undetectable with medical imaging. Because of the convenience and availability of ultrasound as an imaging technology, targeted contrast agents for use with ultrasound have the potential to rapidly transform this modality into an even more powerful clinical tool. Unfortunately, recent studies with targeted ultrasound contrast agents have failed to illustrate the sensitivity hoped for to make this technique revolutionary. In this proposal, we present a plan to increase the sensitivity of ultrasound to targeted contrast agents over an order of magnitude. Our model target for these studies is angiogenesis (the formation of new blood vessels), which is required for tumor growth beyond 1-2 mm in diameter. The integrin alpha(v)beta(3) is over-expressed in regions of angiogenesis, and has been shown to correlate with tumor grade. These properties make the alpha (v)beta(3) integrin an ideal target for site-directed contrast agents. This proposal describes a three-part method to achieve the desired substantial increase in sensitivity by combining a completely new contrast agent with a novel contrast agent delivery technique, and we package these improvements with the substantially improved detection strategies only possible due to the improvements in the agent and the delivery. The combined tools and experience of the Departments of Biomedical and Chemical Engineering, the School of Veterinary Medicine, and the Cancer Center at the University of California, Davis, provide a unique and qualified research group for implementing this new system for molecular imaging with ultrasound. ? ?
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