Increasing binding efficiency of ultrasound targeted agents with radiation force

We demonstrate both theoretically and experimentally that ultrasound radiation force can significantly increase the binding efficiency of targeted contrast agents without increasing non-specific adhesion of agents to the target surface. The radial oscillation of a microbubble was determined using a previously developed model, and then displacement and translational velocity were predicted by solving the trajectory equation of the microbubble. Theoretical evaluation showed that a microbubble can be easily displaced across a vessel by radiation force. Experiments with an avidin-coated tube and biotin-targeted microbubbles clearly demonstrated the effect of radiation force in increasing the efficiency of specific binding. Under control conditions, only sporadic binding to the vessel wall was observed. With radiation force, targeted agents adhered to the vessel wall at 20 times the rate of control experiments. An experiment with microbubbles targeted to α_vβ₃ expressing cells showed similar results.