SU‐E‐U‐04: Evaluation of Normal Tissue Toxicity of Drug‐Loaded Nanodroplets Used for Treating Prostate Cancer with MR‐Guided Focused‐Ultrasound

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.