Molecular imaging using a site-targeted ultrasound contrast agent

We have developed a nongaseous, ligand-targeted perfluorocarbon nanoparticle emulsion which can acoustically enhance the presence of molecular epitopes on tissue surfaces. In a two-part study, we first demonstrate how perfluorocarbons with varying phase velocities impact the acoustic reflectivity of plasma clots targeted with an anti-fibrin perfluorocarbon nanoparticle in vitro. The targeted perfluorocarbon contrast agents increased backscattered power from 18.2 to 23.4 dB with the greatest enhancement noted for formulations with low acoustic impedance. Porcine carotid arteries were injured by percutaneous balloon angioplasty and treated in situ with a tissue factor-targeted or control nanoparticulate immunoemulsion. Intravascular ultrasound images (30 MHz) of the arteries before and after application of contrast agent demonstrated the acoustic localization and enhancement of stretch-induced tissue factor expression within the carotid media, which was not apparent in the control vessels.