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

Abstract

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.

Progression in low‐intensity ultrasound‐induced tumor radiosensitization

“…There is no doubt that UTMD-induced vascular closure and tumor cell death have potential applications in enhancing the RT's effectiveness. [76][77][78][79][80][81] Researchers have further conducted investigations into the effects of UTMD-induced radiosensitization on larger tumor models in rabbits with prostate tumor xenografts. The results proved that that combining UTMD and RT resulted in enhanced radiological effects and improved antitumor efficacy when compared to using each therapy alone.…”

“…In addition to the PC3 prostate cancer xenograft model, similar findings were also observed in mouse and rat models of bladder cancer, breast cancer, hepatocellular carcinoma, fibrosarcoma, and glioblastoma. There is no doubt that UTMD‐induced vascular closure and tumor cell death have potential applications in enhancing the RT's effectiveness 76–81 …”