An in-vivo study of the combined therapeutic effects of pulsed non-thermal focused ultrasound and radiation for prostate cancer

Abstract

Purpose The purpose of this study was to investigate the in vivo combined effects of pulsed focused ultrasound (pFUS) and radiation (RT) for prostate cancer treatment. Materials and Methods An animal prostate tumor model was developed by implanting human LNCaP tumor cells in the prostates of nude mice. Tumor-bearing mice were treated with pFUS, RT or both (pFUS + RT) and compared with a control group. Non-thermal pFUS treatment was delivered by keeping the body temperature below 42 °C as measured real-time by MR thermometry and using a pFUS protocol (1 MHz, 25 W focused ultrasound; 1 Hz pulse rate with a 10% duty cycle for 60 sec for each sonication). Each tumor was covered entirely using 4–8 sonication spots. RT treatment with a dose of 2 Gy was delivered using an external beam (6 MV photon energy with dose rate 300MU/min). Following the treatment, mice were scanned weekly with MRI for tumor volume measurement. Results The results showed that the tumor volume in the control group increased exponentially to 142 ± 6%, 205 ± 12%, 286 ± 22% and 410 ± 33% at 1, 2, 3 and 4 weeks after treatment, respectively. In contrast, the pFUS group was 29% (p < 0.05), 24% (p < 0.05), 8% and 9% smaller, the RT group was 7%, 10%, 12% and 18% smaller, and the pFUS + RT group was 32%, 39%, 41% and 44% (all with p < 0.05) smaller than the control group at 1, 2, 3, and 4 weeks post treatment, respectively. Tumors treated by pFUS showed an early response (i.e. the first 2 weeks), while the RT group showed a late response. The combined pFUS + RT treatment showed consistent response throughout the post-treatment weeks. Conclusions These results suggest that RT combined with non-thermal pFUS can significantly delay the tumor growth. The mechanism of tumor cell killing between pFUS and RT may be different. Pulsed FUS shows early tumor growth delay, while RT contributes to the late effect on tumor growth delay. The addition of pFUS to RT significantly enhanced the therapeutic effect for prostate cancer treatment.