title: Surfactant-stabilized contrast agent on the nanoscale for diagnostic ultrasound imaging.
abstract: Ultrasound contrast agents (CA) are generally micron-sized stabilized gas bubbles, injected IV. However, to penetrate beyond the vasculature and accumulate in targets such as tumors, CA must be an order of magnitude smaller. We describe a method of achieving nanometer-sized, surfactant-stabilized CA by differential centrifugation. High g force was shown to destroy bubble integrity. Optimal conditions (300 rpm for 3 min) produced an agent with a mean diameter of 450 nm, which gave 25.5 dB enhancement in vitro at a dose of 10 microL/mL, with a 13 min half-life. In vivo, the CA produced excellent power Doppler and grey-scale pulse inversion harmonic images at low acoustic power when administered. In vivo dose-response curves obtained in three rabbits showed enhancement between 20 and 25 dB for dosages above 0.025 mL/kg. These results encourage further investigation of the possible diagnostic and therapeutic benefits of using nanoparticles as CA, including passive targeting and accumulation in tumors.
authors.affiliation: School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Wheatley
authors.forename: Flemming
authors.initials: F
authors.lastname: Forsberg
authors.forename: Neal
authors.initials: N
authors.lastname: Dube
authors.forename: Mihir
authors.initials: M
authors.lastname: Patel
authors.forename: Brian E
authors.initials: BE
authors.lastname: Oeffinger
mesh_terms: D000818:Animals; D002498:Centrifugation / Q000379:methods; D003287:Contrast Media / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D006601:Hexoses / Q000008:administration & dosage; D007089:Image Enhancement / Q000379:methods; D007668:Kidney / Q000000981:diagnostic imaging; D049329:Nanostructures; D010316:Particle Size; D011136:Polysorbates / Q000008:administration & dosage; D011817:Rabbits; D013501:Surface-Active Agents; D014465:Ultrasonics; D018617:Ultrasonography, Doppler, Pulsed / Q000379:methods
chemical_list: D003287:Contrast Media; D006601:Hexoses; D011136:Polysorbates; C418026:ST68; D013501:Surface-Active Agents