Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
Br J Cancer. 2012 Jul 24;107(3):469-76. doi: 10.1038/bjc.2012.279. Epub 2012 Jul 12.
Tumour vasculature is an important component of tumour growth and survival. Recent evidence indicates tumour vasculature also has an important role in tumour radiation response. In this study, we investigated ultrasound and microbubbles to enhance the effects of radiation.
Human bladder cancer HT-1376 xenografts in severe combined immuno-deficient mice were used. Treatments consisted of no, low and high concentrations of microbubbles and radiation doses of 0, 2 and 8 Gy in short-term and longitudinal studies. Acute response was assessed 24 h after treatment and longitudinal studies monitored tumour response weekly up to 28 days using power Doppler ultrasound imaging for a total of 9 conditions (n=90 animals).
Quantitative analysis of ultrasound data revealed reduced blood flow with ultrasound-microbubble treatments alone and further when combined with radiation. Tumours treated with microbubbles and radiation revealed enhanced cell death, vascular normalisation and areas of fibrosis. Longitudinal data demonstrated a reduced normalised vascular index and increased tumour cell death in both low and high microbubble concentrations with radiation.
Our study demonstrated that ultrasound-mediated microbubble exposure can enhance radiation effects in tumours, and can lead to enhanced tumour cell death.
肿瘤血管是肿瘤生长和存活的重要组成部分。最近的证据表明，肿瘤血管在肿瘤辐射反应中也起着重要作用。在这项研究中，我们研究了超声和微泡以增强辐射的效果。
使用严重联合免疫缺陷小鼠中的人膀胱癌 HT-1376 异种移植物。治疗包括无微泡、低浓度微泡和高浓度微泡以及 0、2 和 8 Gy 的辐射剂量，在短期和纵向研究中分别进行了 9 种条件（n=90 只动物）的处理。在治疗后 24 小时评估急性反应，纵向研究每周监测肿瘤反应，直至 28 天，总共使用 9 种条件（n=90 只动物）。
超声数据分析的定量结果显示，单独使用超声-微泡治疗以及与辐射联合使用时，血流减少。用微泡和辐射治疗的肿瘤显示出增强的细胞死亡、血管正常化和纤维化区域。纵向数据表明，在低浓度和高浓度微泡与辐射联合使用时，正常化血管指数降低，肿瘤细胞死亡增加。
我们的研究表明，超声介导的微泡暴露可以增强肿瘤的辐射效应，并导致增强的肿瘤细胞死亡。
