Mahboobeh Alamolhoda1, Manijhe Mokhtari-Dizaji2, Amir Hoshang Barati3, Hadi Hasanzadeh4. 1. Department of Medical Physics, Tarbiat Modares University, P.O. Box: 14115-133, Tehran, Iran. 2. Department of Medical Physics, Tarbiat Modares University, P.O. Box: 14115-133, Tehran, Iran. mokhtarm@modares.ac.ir. 3. Medical Physics Department, Kurdistan Medical Sciences University, Sanandaj, Iran. 4. Medical Physics Department, Semnan Medical Sciences University, Semnan, Iran.
Abstract
INTRODUCTION: Dual-frequency ultrasound has recently been shown to extensively enhance the acoustic cavitation yield in water. METHODS: In this study, the in vivo antitumor effect of simultaneous, dual-frequency ultrasound at low-level intensity (I SATA = 2 W/cm(2) for 1 MHz and I SATA = 0.2 W/cm(2) for 150 kHz) in combination with an intravenous injection of 5 mg/kg hematoporphyrin (Hp) was investigated in a model of breast adenocarcinoma in Balb/c mice. Seventy-one tumor-bearing mice were divided into nine treatment groups: control, sham, Hp injection, and single- and dual-frequency sonication in the presence and absence of Hp. The tumor growth delay was then calculated based on the tumor volume at various times after treatment using the following parameters: relative volume percent, [Formula: see text] and [Formula: see text] times (to reach five and two times the initial volume), percent of tumor growth inhibition ratio, and survival period. RESULTS: Our results showed no significant difference between the 150 kHz and 1 MHz single-frequency groups when compared with the sham group after 9 days of treatment (p > 0.05). However, treatment with dual-frequency ultrasound significantly delayed tumor growth when compared with the sham group (p < 0.05) after 9 days of treatment. Furthermore, in vivo experiments showed that combined dual-frequency sonication controlled tumor growth more effectively than single-frequency sonication. Evaluation of the therapeutic effects of single- and dual-frequency ultrasound in sonodynamic therapy revealed that treatment with the combination of dual-frequency ultrasound and Hp resulted in a significant reduction in the relative volume percent of tumors after 3 days of treatment (p < 0.05) compared with the controls. Additionally, the T 5 time and the survival period in the group treated with the combination therapy was significantly longer than those in all the other groups (p < 0.05). These findings were further verified histopathologically. CONCLUSION: In conclusion, our results reveal that sonodynamic therapy using dual-frequency ultrasound is able to extend the survival time of animals compared with single-frequency sonication.
INTRODUCTION: Dual-frequency ultrasound has recently been shown to extensively enhance the acoustic cavitation yield in water. METHODS: In this study, the in vivo antitumor effect of simultaneous, dual-frequency ultrasound at low-level intensity (I SATA = 2 W/cm(2) for 1 MHz and I SATA = 0.2 W/cm(2) for 150 kHz) in combination with an intravenous injection of 5 mg/kg hematoporphyrin (Hp) was investigated in a model of breast adenocarcinoma in Balb/c mice. Seventy-one tumor-bearing mice were divided into nine treatment groups: control, sham, Hp injection, and single- and dual-frequency sonication in the presence and absence of Hp. The tumor growth delay was then calculated based on the tumor volume at various times after treatment using the following parameters: relative volume percent, [Formula: see text] and [Formula: see text] times (to reach five and two times the initial volume), percent of tumor growth inhibition ratio, and survival period. RESULTS: Our results showed no significant difference between the 150 kHz and 1 MHz single-frequency groups when compared with the sham group after 9 days of treatment (p > 0.05). However, treatment with dual-frequency ultrasound significantly delayed tumor growth when compared with the sham group (p < 0.05) after 9 days of treatment. Furthermore, in vivo experiments showed that combined dual-frequency sonication controlled tumor growth more effectively than single-frequency sonication. Evaluation of the therapeutic effects of single- and dual-frequency ultrasound in sonodynamic therapy revealed that treatment with the combination of dual-frequency ultrasound and Hp resulted in a significant reduction in the relative volume percent of tumors after 3 days of treatment (p < 0.05) compared with the controls. Additionally, the T 5 time and the survival period in the group treated with the combination therapy was significantly longer than those in all the other groups (p < 0.05). These findings were further verified histopathologically. CONCLUSION: In conclusion, our results reveal that sonodynamic therapy using dual-frequency ultrasound is able to extend the survival time of animals compared with single-frequency sonication.