Role of frequency and mechanical index in ultrasonic-enhanced chemotherapy in rats

Abstract

Purpose The therapeutic effect of ultrasound and micellar-encapsulated doxorubicin was studied in vivo using a tumor-bearing rat model with emphasis on how tumor growth rate is affected by ultrasonic parameters such as frequency and intensity. Methods This study employed ultrasound of two different frequencies (20, 476 kHz) and two pulse intensities, but identical mechanical indices and temporal average intensities. Ultrasound was applied weekly for 15 min to one of two bilateral leg tumors (DHD/K12/TRb colorectal epithelial cell line) in the rat model immediately after intravenous injection of micelle-encapsulated doxorubicin. This therapy was applied weekly for 6 weeks. Results showed that tumors treated with drug and ultrasound displayed, on average, slower growth rates than non-insonated tumors (P = 0.0047). However, comparison between tumors that received 20 or 476-kHz ultrasound treatments showed no statistical difference (P = 0.9275) in tumor growth rate. Conclusion Application of ultrasound in combination with drug therapy was effective in reducing tumor growth rate, irrespective of which frequency was employed.