Sonodynamic Therapy Consisting of Focused Ultrasound and a Photosensitizer Causes a Selective Antitumor Effect in a Rat Intracranial Glioma Model

In this study we sought to determine the optimal focused ultrasound acoustic conditions with photosensitizers for the ablation of experimental intracranial glioma in rats. Materials and Methods: 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. Results: 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. Conclusion: 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.