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WE-AB-BRA-02: Study of the Therapeutic Effects of Pulsed Focused Ultrasound Combined with Encapsulated Chemotherapeutic Agents for Prostate Cancer in Vivo.

PURPOSE
To investigate the improvement of prostate cancer inhibition by combining pulsed focused ultrasound (pFUS) exposures and chemotherapeutic agents encapsulated nanodroplets under MR guidance for prostate cancer therapy.


METHODS
Prostate cancer (LNCaP) cells were implanted orthotopically. First we developed nanodroplets encapsulated with chemotherapeutic agents for both paclitaxel (PTX) and docetaxel (DTX). Secondly, tumor-bearing mice were randomly divided into 5 groups (n=5). Group 1 animals were treated with an i.v injection of DTX-encapsulated nanodroplets (DTX-ND) + pFUS. Group 2 were treated with pFUS alone. Group 3 were injected (i.v) with DTX-ND alone, Group 4 received free DTX and Group 5 was used as control. Ultrasound treatment parameters were 1MHz, 25W acoustic power, 10% duty cycle and 60 seconds for each sonication. After treatment, animals were allowed to survive for 4 weeks. Tumor volumes were measured on MRI. Third, we repeated the experiment with PTX-ND. Finally we performed study on biodistribution of PTX-ND for prostate cancer and the treatment effects on tumor growth delay are being evaluated.


RESULTS
With DTX-ND, significant tumor growth delay was observed in Group 1 with p=0.039. There was no significant tumor growth delay observed for Group 2 (p=0.477), Group 3 (p=0.209) and Group 4 (p=0.476). The results are consistent with earlier PTX-ND studies in which significant tumor growth delay was observed in Group 1 with p=0.004. There was no significant tumor growth delay observed for Group 2 (p=0.285), Group 3 (p=0.452) and Group 4 (p=0.158). The peak of drug update in tumor appeared at 4h after injection in the biodistribution study.


CONCLUSION
Our results showed a great potential of targeted nanodroplets for prostate cancer therapy, which could be activated by pFUS. Our study also suggested that the optimal timing for applying pFUS is 4h after i.v injection of PTX-ND and the treatment effect is being evaluated.