title: Effects of acoustic radiation force on the binding efficiency of BR55, a VEGFR2-specific ultrasound contrast agent.
abstract: This work describes an in vivo study analyzing the effect of acoustic radiation force (ARF) on the binding of BR55 VEGFR2-specific contrast-agent microbubbles in a model of prostatic adenocarcinoma in rat. A commercial ultrasound system was modified by implementing high duty-cycle 3.5-MHz center frequency ARF bursts in a scanning configuration. This enabled comparing the effects of ARF on binding in tumor and healthy tissue effectively in the same field of view. Bubble binding was established by measuring late-phase enhancement in amplitude modulation (AM) contrast-specific imaging mode (4 MHz, 150 kPa) 10 min after agent injection when the unbound bubbles were cleared from the circulation. Optimal experimental conditions, such as agent concentration (0.4 × 10(8)-1.6 × 10(8) bubbles/kg), acoustic pressure amplitude (26-51 kPa) and duty-cycle (20%-95%) of the ARF bursts, were evaluated in their ability to enhance binding in tumor without significantly increasing binding in healthy tissue. Using the optimal conditions (38 kPa peak-negative pressure, 95% duty cycle), ARF-assisted binding of BR55 improved significantly in tumor (by a factor of 7) at a lower agent dose compared with binding without ARF, and it had an insignificant effect on binding in healthy tissue. Thus, the high binding specificity of BR55 microbubbles for targeting VEGFR2 present at sites of active angiogenesis was confirmed by this study. Therefore, it is believed that based on the results obtained in this work, ultrasound molecular imaging using target-specific contrast-agent microbubbles should preferably be performed in combination with ARF.
authors.affiliation: Bracco Suisse SA, Geneva Research Center and Manufacturing Site, Plan-les-Ouates/Geneva, Switzerland. peter.frinking@bracco.com
authors.forename: Peter J A
authors.initials: PJ
authors.lastname: Frinking
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tardy
authors.forename: Martine
authors.initials: M
authors.lastname: Théraulaz
authors.forename: Marcel
authors.initials: M
authors.lastname: Arditi
authors.forename: Jeffry
authors.initials: J
authors.lastname: Powers
authors.forename: Sibylle
authors.initials: S
authors.lastname: Pochon
authors.forename: François
authors.initials: F
authors.lastname: Tranquart
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000528:radiation effects; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods; D054459:Elasticity Imaging Techniques / Q000379:methods*; D019220:High-Energy Shock Waves; D008297:Male; D045423:Microbubbles; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011485:Protein Binding / Q000528:radiation effects; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D040301:Vascular Endothelial Growth Factor Receptor-2