Abstract
Microbubble contrast agents suitable for targeted molecular imaging have been described. Commonly used agents are gas-filled micron-size bubbles. Targeting ligands (antibodies, peptides, or proteoglycans) are coupled to the contrast particles and ensure firm attachment of microbubbles to intravascular regions of interest. Targeting is directed to selectins or integrins upregulated on vascular endothelium in the areas of pathology (inflammation, ischemia-reperfusion injury, or angiogenesis). Real-time imaging has been performed in animal models with sub-millimeter spatial resolution. Detection sensitivity for targeted microbubble contrast is superb: single bubbles (pg mass) can be visualized by ultrasound. Successful retention of microbubbles on the target is dependent on the target receptor surface density as well as targeting ligand surface density on the bubbles. To improve targeting efficacy, microbubbles can be outfitted with fast-binding ligands (such as P-selectin glycoprotein ligand-1 analogs) in addition to slow but firmly binding ligands (such as antibodies). Ultrasound irradiation also improves efficacy of targeting, especially in high shear conditions. In addition to imaging, microbubbles can be applied for drug and gene delivery purposes: interaction of ultrasound and bubbles can be used for in situ targeted deposition, activation and release of pharmaceutical agents [Disclosures: ALK, JJR, and KFL: Targeson stock ownership. ALK: Philips Research grant.]
Published Version
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