Ultrasonic enhancement of αvβ3 expressing-cells with targeted contrast agents

Targeted contrast agents have the potential to substantially improve the ability of ultrasound contrast agents to delineate otherwise difficult-to-detect pathologies. In this manuscript, optical microscopy and acoustic backscatter measurements from human umbilical vein endothelial cells (HUVEC) exposed to targeted and control microbubbles illustrate the high affinity of targeted agents for the α_vβ₃ integrin. Backscatter measurements are provided for cell layers exposed to three types of targeted contrast agents in addition to two controls. Acoustic studies illustrate a backscatter amplitude increase from α_vβ₃ expressing cells exposed to the targeted contrast agent of up to 13 fold compared to non-targeted agents. Additionally, echo decorrelation is shown to be a function of acoustic pressure and microbubble density. Frequency domain analysis demonstrates that adherent targeted microbubbles exhibit a significantly more narrowband spectrum than free microbubbles. These results suggest that targeted contrast agents may provide additional sensitivity in the detection of tumors, and that adherent contrast agents may be differentiable from free-floating microbubbles.