Wu Sheng-Kai, Tsai Chia-Lin, Mir Aisha, Marcus Stuart L, Hynynen Kullervo
Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Sci Rep. 2025 Jan 7;15(1):1161. doi: 10.1038/s41598-025-85314-6.
Sonodynamic therapy is an emerging therapeutic approach against brain tumours. However, the treatment scheme and ultrasound parameters have yet to be explored for clinical translation. Our study aimed to optimize ultrasound parameters for sonodynamic therapy (SDT) with 5-ALA as a sonosensitizing agent and to evaluate its therapeutic outcome on the rodent 9L gliosarcoma and the human U87 glioblastoma models. We stereotactically implanted brain tumour cells in rats and monitored tumour volume via MRI. SDT was conducted weekly using a 60 mg/kg dose of 5-ALA, injected intravenously 6 h before sonication. We used a driving frequency of 580 kHz with 0.75 MPa and evaluated the effect of different burst lengths to optimize ultrasound parameters. We also tested SDT against advanced-stage brain tumours to verify its efficacy further. Our results showed that a longer burst length could improve therapeutic outcomes. Tumour growth inhibition was established only in the first three weeks with 10 ms and 50 ms burst length sonication, but 86 ms burst length greatly improved the survival outcome. Therefore, the therapeutic efficacy is proportionate to the burst length and, thus, the total delivered energy. Repeated SDT using multiple targets to cover the entire tumour volume with optimal ultrasound parameters can achieve significant anti-tumour effects in both 9L and U87 models. Lastly, our results on late-stage tumour treatments showed that SDT can still provide prolonged survival. These promising findings demonstrate that repeated SDT using transcranial-focused ultrasound together with 5-ALA can optimize anti-tumour effects and even lead to complete clearance of the tumours. This weekly treatment with pulsed ultrasound sonication strategy is practical for future clinical translation.
声动力疗法是一种新兴的脑肿瘤治疗方法。然而，其治疗方案和超声参数尚未进行临床转化探索。我们的研究旨在优化以5-氨基乙酰丙酸（5-ALA）作为声敏剂的声动力疗法（SDT）的超声参数，并评估其对啮齿动物9L胶质肉瘤和人U87胶质母细胞瘤模型的治疗效果。我们通过立体定向将脑肿瘤细胞植入大鼠体内，并通过磁共振成像（MRI）监测肿瘤体积。SDT每周进行一次，使用60mg/kg剂量的5-ALA，在超声处理前6小时静脉注射。我们使用580kHz的驱动频率和0.75MPa，并评估不同脉冲长度对超声参数优化的影响。我们还测试了SDT对晚期脑肿瘤的作用，以进一步验证其疗效。我们的结果表明，较长的脉冲长度可以改善治疗效果。仅在最初三周，10ms和50ms脉冲长度的超声处理可抑制肿瘤生长，但86ms脉冲长度可显著改善生存结果。因此，治疗效果与脉冲长度成正比，进而与总传递能量成正比。使用多个靶点以最佳超声参数覆盖整个肿瘤体积进行重复SDT，在9L和U87模型中均可实现显著的抗肿瘤效果。最后，我们对晚期肿瘤治疗的结果表明，SDT仍可延长生存期。这些有前景的发现表明，使用经颅聚焦超声联合5-ALA进行重复SDT可优化抗肿瘤效果，甚至可导致肿瘤完全清除。这种每周进行脉冲超声处理的治疗策略对未来的临床转化具有实际意义。
