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SU-E-J-01: MR Guided Pulsed Focused Ultrasound Mediated Targeted Chemotherapeutic-Agent Delivery in Management of Prostate Cancer
Med Phys. 2015 Jun;42(6) :3263
PMID: 26127394   
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PURPOSE: The purpose of this study is to investigate an innovative approach to prostate cancer therapy using nanodroplet-encapsulated drugs combined with pulsed high intensity focused ultrasound (pFUS) treatment. Pulsed FUS treatment improves localized drug release from the carrier and enhances intracellular uptake, which ensures temporal and spatial control of local drug delivery while reducing systemic toxicity from the drugs. 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=5 for each group). Group 1, animals were treated with an IV injection of docetaxel (DTX)-encapsulated nanodroplets (ND-DTX) + pFUS. Animals in Group 2 were treated with pFUS alone. Animals in Group 3 were injected (IV) with DTX-encapsulated nanodroplets alone, Group 4 received free DTX alone and Group 5 was used as a control group. After treatment, animals were allowed to survive for 3 weeks. Tumor growth delay was monitored by MRI (resolution: <0.2mm). The formulation of the DTX-encapsulated nanodroplets was: DTX 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: Our results showed that Group 1, in which animals were treated with an IV injection of ND-DTX + pFUS, exhibited the most tumor growth control (50%-30%) among all groups. All other groups showed similar tumor growth to that of the control group after the treatment (within statistical uncertainties). CONCLUSION: Our preliminary results showed a great potential for prostate cancer therapy using targeted DTX+ nanodroplets, which could be activated by pFUS. Further animal studies are warranted to confirm the results. The enhancement effect of pFUS on targeted drug delivery needs to be investigated quantitatively.
Chen, L Cvetkovic, D Gupta, R Wang, B Ma, C United States Med Phys. 2015 Jun;42(6):3263. doi: 10.1118/1.4924089.