TH‐A‐BRF‐06: Optimal Timing for Ultrasound‐Activated Drug Delivery for Treatment of Prostate Cancer Under MR Guidance

Abstract

Purpose:To determine optimal timing for applying tumor targeted focused ultrasound (FUS) under MR guidance to release drugs from nanodroplets (ultrasound responsive, drug delivery vehicles) for effective treatment of prostate cancer.Methods:Poly lactide (PDLA) nanodroplets loaded with model drug {fluorescently labeled paclitaxel (FPTX)} were prepared using solid dispersion technique. Human prostate cancer, LNCaP cells were implanted orthotopically in prostates of male nude mice. Tumor bearing mice (n=3) were injected with 125 microlitre of 0.1% FPTX, 2% PDLA nanodroplets via tail‐vein. At 30min, 2h, 6h and 24h animals were anesthetized, blood was collected by eye bleed, then animals were sacrificed, tumor and organs were excised and weighted. One cut portion of the organ was homogenized, incubated in lysis buffer and centrifuged. Lysates were read using fluorescence spectrophotometer. Other portion was cut into sections for qualitative analysis using fluorescence microscope. Mice (n=3) were also injected with 0.1% FPTX solution (non encapsulated drug form) and mice (n=3) with no injections were used as controls.Results:Drug‐loaded nanodroplets shows more drug accumulation in tumor with maximum concentration of one third of injected dose after 2h of injection when compared with maximum concentration of less than one tenth of injected dose after 2h of injection for free drug. The time range 2h to 6h is considered optimum for applying FUS to activate drug release from nanodroplets, when maximum drug concentration is seen in tumor while low concentration is found in blood thus minimizing potential damage to blood vessels. Microscopy studies show consistency with quantitative data.Conclusion:Our prior in vivo studies have showed significant tumor growth delay when FUS is applied under MR imaging in combination with docetaxel loaded nanodroplets. Present work with model drug loaded nanodroplets indicates the potential for increasing prostate cancer treatment efficacy and providing preclinical data for using FUS‐mediated drug delivery under MR guidance.