Targeted Drug Delivery Technique Employing Pulsed Focused Ultrasound for Treatment of Prostate
L Chen1*, N Rapoport2, X Chen1, D Cvetkovic1, J Xue3, q xu4, X Tong4, H Liu5, R Gupta2, C Ma1, (1) Fox Chase Cancer Center, PHILADELPHIA, PA, (2) University of Utah, Salt Lake City, UT, (3) Cancer Center of Union Hospital, Tongji Medical College of Huazhong Univers, Wuhan,(4) 3rd Affiliated Hospital of Qiqihar Medical University, Qiqihar,(5) Henan Provincial Cancer Hospital, Zhengzhou,TU-A-BRA-11 Tuesday 8:00:00 AM - 9:55:00 AM Room: Ballroom A
Purpose: The purpose of this study is to investigate an innovative approach to prostate cancer therapy using nanodroplet-encapsulated drugs combined with pFUS (pulsed high intensity focused ultrasound) treatment. Pulsed FUS treatment provides a localized drug release from the carrier and enhanced intracellular uptake, which ensures temporal and spatial control of local drug delivery while lowering the systemic toxicity.
Methods: LNCaP cells were implanted into the prostates of nude mice. Tumor growth was monitored using MRI. The tumor-bearing mice were randomly divided into 5 groups (n=3). Group 1, animals were treated with an IV injection of paclitaxel (PTX)-encapsulated nanodroplets (ND-PTX) + pFUS. Animals in Group 2 were treated with pFUS alone. Animals in Group 3 were injected (IV) with PTX-encapsulated nanodroplets alone, Group 4 received pFUS+empty nanodroplets and Group 5 was used as a control group. After treatment, animals were allowed to survive for 4 weeks. Tumor growth delay was monitored by MRI. The formulation of the PTX-encapsulated nanodroplets is as follows: PTX dose 20 mg/kg, Nanoemulsion composition 0.5% PTX, 1% perfluorocarbon and 2% stabilizing block copolymer. Ultrasound treatment parameters were 1MHz, 25W acoustic power, 10% duty cycle and 60 sec for each sonication.
Results: Compared with the control group, significant tumor growth delay was observed in Group 1 with p=0.004, 3 weeks after treatment. 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).
Conclusions: Our preliminary results showed a great potential for prostate cancer therapy using targeted PTX+ nanodroplets, which could be activated by pFUS. More animal studies are warranted to confirm the results. The enhancement effect of pFUS on targeted drug delivery needs to be investigated quantitatively. This work is supported by Focused Ultrasound Surgery Foundation, DOD PC073127 and DOD BC102806. Technical support from InSightec is graciously acknowledged.