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SU-E-U-04: Evaluation of Normal Tissue Toxicity of Drug-Loaded Nanodroplets Used for Treating Prostate Cancer with MR-Guided Focused-Ultrasound
Med Phys. 2015 Jun;42(6) :3241
PMID: 26127302   
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Abstract
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.
Notes
Gupta, R Cvetkovic, D Wang, B Ma, C Chen, L United States Med Phys. 2015 Jun;42(6):3241. doi: 10.1118/1.4923997.