Nonaka Masani, Yamamoto Masaaki, Yoshino Shinichiro, Umemura Shin-Ichiro, Sasaki Kazunari, Fukushima Takeo
Department of Neurosurgery, Fukuoka University School of Medicine, Jonan-ku, Fukuoka 814-0180, Japan.
Anticancer Res. 2009 Mar;29(3):943-50.
In this study we sought to determine the optimal focused ultrasound acoustic conditions with photosensitizers for the ablation of experimental intracranial glioma in rats.
Normal rat brains were sonicated via a transducer placed on the dural surface with or without a prior intravenous injection of the photosensitizer Rose Bengal (50 mg/kg of body weight). The ultrasound intensity was varied to 25, 110 or 150 W/cm(2), and the duration of irradiation was 10 s, or 1, 3, or 5 min. In experimental intracranial gliomas, one week after inoculation of C6 rat glioma cells in the rat brain, the rat brain was sonicated through a 10 mm-diameter craniotomy.
A selective antitumor effect against cerebral glioma while sparing normal brain tissues was achieved by sonodynamic focused therapy consisting of focused ultrasound at 25 W/cm(2) at 1 MHz for 5 min and Rose Bengal (50 mg/kg of body weight). The areas of tumors in sham-operated rats and in rats that received sonodynamic therapy without and with Rose Bengal at an intensity of 25 W/cm(2) for 5 min were 19.53+/-3.89, 10.64+/-2.21 and 3.01+/-1.74 mm(2), respectively. The tumor area was significantly smaller in the ultrasound therapy groups than in control non-treated animals (p=0.002). There was no significant temperature change in tumor tissues during sonication with 25 W/cm(2) at 1 MHz.
This is the first report to demonstrate the usefulness of sonodynamic therapy consisting of focused ultrasound and photosensitizer for the treatment of experimental malignant glioma.
在本研究中,我们试图确定使用光敏剂时聚焦超声的最佳声学条件,用于大鼠实验性颅内胶质瘤的消融。
正常大鼠脑通过置于硬脑膜表面的换能器进行超声处理,在静脉注射光敏剂孟加拉玫瑰红(50mg/kg体重)前后进行。超声强度分别为25、110或150W/cm²,照射持续时间为10秒、1、3或5分钟。在实验性颅内胶质瘤中,将C6大鼠胶质瘤细胞接种到大鼠脑内一周后,通过直径10mm的开颅术对大鼠脑进行超声处理。
通过由1MHz频率、25W/cm²聚焦超声照射5分钟和孟加拉玫瑰红(50mg/kg体重)组成的声动力聚焦疗法,实现了对脑胶质瘤的选择性抗肿瘤作用,同时保留正常脑组织。假手术大鼠以及接受强度为25W/cm²、持续5分钟的声动力疗法但未使用和使用孟加拉玫瑰红的大鼠的肿瘤面积分别为19.53±3.89、10.64±2.21和3.01±1.74mm²。超声治疗组的肿瘤面积明显小于未治疗的对照动物(p = 0.002)。在1MHz频率、25W/cm²超声处理期间,肿瘤组织内温度无明显变化。
这是首次证明由聚焦超声和光敏剂组成的声动力疗法用于治疗实验性恶性胶质瘤有效性的报告。