Ultrasound dose fractionation in sonodynamic therapy

Sonodynamic therapy (SDT) is a new modality in cancer therapy and it is based on preferential uptake and/or retention of a sonosensitizing drug in tumor tissues and subsequent activation of the drug by ultrasound. The dose fractionation effect in radiation therapy has been known for more than a century, but it is not reported in SDT so far. In this study, the in vivo antitumor effect of the simultaneous dual-frequency ultrasound (1 MHz and 150 kHz) at low-level intensity (cumulative I(SATA) = 2.2W/cm(2); total energy density 3960J/cm(2); for 30 min sonication) in combination with the sonosensitizer of photofrin (PF) (sodium porfimer) was investigated in dose fractionation regime in a spontaneous murine model of breast adenocarcinoma in Balb/c mice. The tumor-bearing mice were divided into six groups (n = 8 to 10): Untreated groups included control and sham; experimental groups were treated with 5 mg/kg intravenous injection of PF alone, with combined PF and ultrasound for 30-min sonication in one fraction at 24 h after PF administration; with combined PF and ultrasound for 30 min sonicatin in three fraction at 18, 24 and 30 h after PF administration; and finally with combined PF and ultrasound for 30 min sonication in five fraction at 12, 18, 24, 30 and 36 h after PF administration. The tumor growth delay (TGD) parameters and the percent of apoptotic index AI (%) were measured in treated and untreated groups. The results show that the TGD parameters in treatment groups with combined drug and ultrasound fractionation mode were significantly different compared with other groups (p < 0.05). Also the sonodynamic ultrasound dose fractionation in five fractions is more effective than of the three-fraction regime. The AI of the tumor tissues treated by ultrasound dose fractionation was also significantly higher in the other groups (p < 0.05), in which the AI (%) in the group treated with five fractions was higher with respect to group treated with 3 fractions (11.56 +/- 1.2; 8.7 +/- 0.87), respectively. In conclusion, the ultrasound dose fractionation can be useful in therapeutic effect in SDT and may have future clinical applications.