Phase-change contrast agents (PCCAs) can be vaporized to the echogenic gas state by acoustic/thermal energy from an ultrasound transducer. Few studies to date have explored the molecular imaging capability of PCCAs. In this study, we generate nanoscale droplets composed of low boiling point perfluorocarbons encapsulated in lipid shells capable of targeting αvβ 3. When incubated with HUVEC cells expressing α vβ3, the agents could be activated and imaged with the same transducer, and produced a significant increase in pixel intensity within the cell monolayer. Analysis showed a significant imaging contrast over both baseline and non-targeted controls. Low-boiling point, nanoscale PCCAs may provide new approaches to intravascular and extravascular ultrasound-based molecular imaging.