Sonodynamically Induced Antitumor Effects of 5-Aminolevulinic Acid and Fractionated Ultrasound Irradiation in an Orthotopic Rat Glioma Model

The sonodynamically induced selective antitumor effects of 5-aminolevulinic acid (5-ALA) on a C6 glioma that was implanted in a rat brain were evaluated. One week after the inoculation of the brains with the C6 rat glioma cells, glioma development was monitored using a 1.5 T MRI. Brains both with and without intravenous administration of 5-ALA (60 mg/kg body weight) or Radachlorin (40 mg/kg body weight) were insonated by a 1 MHz ultrasound at a dose of 2.65 W/cm2. Irradiation was performed in a fractionated manner to avoid any thermal effects in the tissue due to the focused ultrasound; 16 min of irradiation were followed by a 3 min recess, then 4 min of resumed irradiation. Mean tumor sizes, measured after the rats were sacrificed 2 weeks post treatment, were 122.48 ± 39.64 mm3 in sham-operated rats, 87.42 ± 21.40 mm3 in rats receiving ultrasound without 5-ALA, 10.50 ± 8.20 mm3 in rats receiving ultrasound with 5-ALA, and 56.42 ± 12.48 mm3 in rats receiving ultrasound with Radachlorin. The tumor size was significantly smaller in the therapy group receiving sonodynamic 5-ALA than in any of the other groups (p < 0.05). This experimental rat model showed that sonodynamic therapy can be useful in the treatment of deep-seated malignant gliomas.