Evaluating the effects of radiation and acoustically-stimulated microbubble therapy in an in vivo breast cancer model

Ultrasound-stimulated microbubbles (USMB) cause localized vascular effects and sensitize tumors to radiation therapy (XRT). We investigated acoustic parameter optimization for combining USMB and XRT. We treated breast cancer xenograft tumors with 500 kHz pulsed ultrasound at varying pressures (570 or 740 kPa), durations (1 to 10 minutes), and microbubble concentrations (0.01 to 1% (v/v)). Radiation therapy (2 Gy) was administered immediately or after a 6-hour delay. Histological staining of tumors 24 hours after treatment detected changes in cell morphology, cell death, and microvascular density. Significant cell death resulted at 570 kPa after a 1-minute exposure with 1% (v/v) microbubbles with or without XRT. However, significant microvascular disruption required higher ultrasound pressure and exposure duration greater than 5 minutes. Introducing a 6-hour delay between treatments (USMB and XRT) showed a similar tumor effect with no further improvement in response as compared to when XRT was delivered immediately after USMB.

Automated summary

Ultrasound-stimulated microbubbles (USMB) can enhance the effects of radiation therapy (XRT) on tumors by causing localized vascular effects. This study investigated the optimization of acoustic parameters for combining USMB and XRT in breast cancer xenograft tumors. The results showed that a pressure of 570 kPa, 1-minute exposure, and 1% (v/v) microbubble concentration resulted in significant cell death, while higher ultrasound pressure and exposure duration were required for significant microvascular disruption. Additionally, introducing a 6-hour delay between USMB and XRT did not further improve the tumor response compared to immediate XRT delivery.