研究动态
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磁共振引导的超声刺激微泡疗法增强放射治疗诱发的肿瘤反应。

MR-guided ultrasound-stimulated microbubble therapy enhances radiation-induced tumor response.

发表日期:2023 Mar 18
作者: Evan McNabb, Deepa Sharma, Lakshmanan Sannachi, Anoja Giles, Wenyi Yang, Gregory J Czarnota
来源: Cell Death & Disease

摘要:

高强度聚焦超声(HIFU)系统已被批准用于治疗性超声传递,以引起组织消融或诱导高热。微泡剂也已与声耦合曝露相结合使用。这些需要温度反馈和监测,以防止不稳定空化并防止超额组织加热。以往的研究利用较低功率和压力来振荡微泡并在不需热诱导损伤的情况下将能量传递给内皮细胞,从而能使肿瘤具有放射增敏性。本研究调查了商业MR集成HIFU系统上减少声功率和压力是否可在超声刺激微泡(USMB)疗法后增强放射诱导的肿瘤反应。用制造商提供的高温疗法系统校准进行商业可用MR集成HIFU系统,超声换能器被校准为达到-750 kPa峰值负压。30只人非PC3瘤体白兔分组接受无治疗、14分钟USMB、8Gy单独放射或联合治疗。MR测温术收集了肿瘤中心和远处肌肉区的体内温度变化。在放疗治疗后24小时收集组织标本。通过苏木精-伊红染色和免疫组织化学分析测量肿瘤细胞死亡率,并与未经处理的对照组进行比较。先前USMB所需的期望峰值负压-750 kPa在输入功率约为5W时发生。12只兔子中10只的温度变化限制在4℃以下。接受USMB单独或与放射联合治疗的大腿远端肌肉区域中位温度为2.50℃。最后,通过免疫组织化学分析证明了联合治疗组与未经处理对照组相比显著的肿瘤细胞死亡。商业MR引导治疗HIFU系统通过与辐射曝露结合使用USMB疗法能够有效治疗兔模型的PC3肿瘤。未来的工作可能会发现商业MR引导治疗系统在使用机械刺激微泡和损伤内皮细胞时,无需高热剂量即可产生抗肿瘤反应。 ©2023年。作者。
High intensity focused ultrasound (HIFU) systems have been approved for therapeutic ultrasound delivery to cause tissue ablation or induced hyperthermia. Microbubble agents have also been used in combination with sonication exposures. These require temperature feedback and monitoring to prevent unstable cavitation and prevent excess tissue heating. Previous work has utilized lower power and pressure to oscillate microbubbles and transfer energy to endothelial cells in the absence of thermally induced damage that can radiosensitize tumors. This work investigated whether reduced acoustic power and pressure on a commercial available MR-integrated HIFU system could result in enhanced radiation-induced tumor response after exposure to ultrasound-stimulated microbubbles (USMB) therapy. A commercially available MR-integrated HIFU system was used with a hyperthermia system calibration provided by the manufacturer. The ultrasound transducer was calibrated to reach a peak negative pressure of - 750 kPa. Thirty male New Zealand white rabbits bearing human derived PC3 tumors were grouped to receive no treatment, 14 min of USMB, 8 Gy of radiation in a separate irradiation cabinet, or combined treatments. In vivo temperature changes were collected using MR thermometry at the tumor center and far-field muscle region. Tissues specimens were collected 24 h post radiation therapy. Tumor cell death was measured and compared to untreated controls through hematoxylin and eosin staining and immunohistochemical analysis. The desired peak negative pressure of - 750 kPa used for previous USMB occurred at approximately an input power of 5 W. Temperature changes were limited to under 4 °C in ten of twelve rabbits monitored. The median temperature in the far-field muscle region of the leg was 2.50 °C for groups receiving USMB alone or in combination with radiation. Finally, statistically significant tumor cell death was demonstrated using immunohistochemical analysis in the combined therapy group compared to untreated controls. A commercial MR-guided therapy HIFU system was able to effectively treat PC3 tumors in a rabbit model using USMB therapy in combination with radiation exposures. Future work could find the use of reduced power and pressure levels in a commercial MR-guided therapy system to mechanically stimulate microbubbles and damage endothelial cells without requiring high thermal doses to elicit an antitumor response.© 2023. The Author(s).