In Vivo Study of Pulsed Focused Ultrasound Mediated Nanodroplet-Encapsulated Chemo-Therapeutic Agent for Treatment of Prostate Cancer
L Chen*, X Chen, R Gupta, D Cvetkovic, B Wang, C Ma, Fox Chase Cancer Center, Philadelphia, PASU-E-U-2 Sunday 3:00PM - 6:00PM Room: Exhibit Hall
Purpose: We developed techniques for the formulation of docetaxel encapsulated nanodroplets, which respond to ultrasound. This study aims to investigate the improvement of prostate cancer treatment by a novel drug delivery technique combining pulsed high intensity focused ultrasound (pHIFU) exposures and docetaxel encapsulated nanodroplets under MR image guidance using prostate cancers grown orthotopically in nude mice.
Methods:Human prostate cancer (LNCaP) cells were implanted orthotopically. Tumor growth was monitored using MRI. When the tumors reached a designated volume of 91 ± 21 mm3, tumor bearing mice were randomly divided into 5 groups (n=5). Group 1 animals were treated with an IV injection of docetaxel-encapsulated nanodroplets (DTX+ND) + pFUS. Animals in Group 2 were treated with pFUS alone. Animals in Group 3 were injected (IV) with docetaxel-encapsulated nanodroplets (DTX+ND) alone, Group 4 received free docetaxel and Group 5 was used as control. The mean diameter of the drug-loaded nanodroplets was 220 ± 30nm.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.
Results:Compared with the control group, significant tumor growth delay was observed in Group 1 with p=0.039 at 4 weeks after treatment. 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).
Conclusion:Our preliminary results showed a great potential for prostate cancer therapy using targeted docetaxel + nanodroplets, which could be activated by pHIFU. More animal studies are warranted to confirm the results and to further optimize the docetaxel + nanodroplets delivery and pHIFU parameters.