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Evaluation of Normal Tissue Toxicity of Drug-Loaded Nanodroplets Used for Treating Prostate Cancer with MR-Guided Focused-Ultrasound

R Gupta

R Gupta*, D Cvetkovic , B Wang , C Ma , L Chen , Fox Chase Cancer Center, Philadelphia, PA


SU-E-U-4 (Sunday, July 12, 2015) 3:00 PM - 6:00 PM Room: Exhibit Hall

Purpose:Our prior studies have showed significant prostate tumor growth-delay when pulsed focused ultrasound (pFUS) is applied under MR-guidance in combination with docetaxel-encapsulated nanodroplets (DTX-ND). The purpose of the present work was to investigate normal tissue toxicity of DTX-ND in order to study true efficacy of a novel prostate cancer treatment approach combining DTX-ND injections and pFUS exposures under MR guidance.

Methods:Poly {ethylene oxide}-co-poly {D, L-lactide} (PDLA) nanodroplets loaded with docetaxel were synthesized in our lab using solid dispersion technique with 0.5% docetaxel, 2% perfluorocarbon and 2% PDLA. The mean diameter of the nanodroplets was 220 ± 30nm. Human prostate cancer, LNCaP cells were implanted orthotopically in prostates of male nude mice. Tumor growth was monitored using MRI. Tumor–bearing mice were randomly divided into 5 groups. Group 1 animals were treated with DTX-ND and pFUS. Ultrasound treatment parameters were 1MHz, 25W acoustic power, 10% duty cycle and 60 seconds for each sonication. Group 2 mice were treated with pFUS. Group 3 mice were injected with DTX-ND. Group 4 received free docetaxel and Group 5 mice were used as control (no treatment). Mice weights were monitored for toxicity.

Results:Docetaxel-loaded nanodroplets showed no normal tissue toxicity as average mice weights (27.12 ±0.75 g) from group 1 were statistically, no different when compared with average mice weights (24.39 ±0.62 g) from control group (p >0.05). Also, average mice weights from group2 (24.95 ±1.2 g), group3 (26.16 ± 0.66 g) and group4 (27.10 ±0.65 g) showed no significant difference in weights when compared to control group (p >0.05).

Conclusion:This study demonstrates that our formulation of DTX-ND shows no normal tissue toxicity in mice. These findings help us in evaluating the true efficacy of our hypothesized prostate cancer treatment strategy using focused-ultrasound activated drug-delivery under MR guidance without incurring additional toxicity.

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