Targeted phase-change contrast agents (PCCAs) have shown great potential for both cancer imaging and therapy. However the acoustic response of targeted PCCAs exposed to ultrasound high frame rate imaging pulses after vaporization has not been fully explored. We herein report the investigation of the change in acoustic signal of folate receptor targeted (FR)-and non-targeted (NT)-PCCAs exposed to breast cancer cells immediately after acoustic vaporization using high frame rate ultrasound imaging. The results show that the vaporized FR-PCCAs measured on the cells has higher acoustic signal than vaporized NT-PCCAs. Moreover, it was found that the acoustic signal of vaporized FR-PCCA on the cells is more persistent than that of vaporized NT-PCCAs 1 second post activation. This is likely because the FR-PCCAs can be vaporized and remain attached to the cancer cells. Furthermore, the high frame rate ultrasound imaging used in this study showed the fast decay of the acoustic signal on the cells immediately after activation, particularly for the NT-PCCAs. These results offer a new insight into the behavior of targeted PCCAs for ultrasound molecular imaging and therapy.