Abstract LB-41: Prolonged survival upon ultrasound-enhanced doxorubicin delivery in two syngenic glioblastoma mouse models

Abstract

Abstract Glioblastoma multiforme (GBM) is the most common and most aggressive malignant primary brain tumor, with a very poor prognosis. Chemotherapeutical treatment of GBM is limited by the blood-brain barrier (BBB). This physical and metabolic barrier separates the blood from the brain parenchyma and prevents the entry of toxins but also of potentially useful chemotherapeutics from the blood into the brain. Microbubble-enhanced focused ultrasound (MB-FUS) has been proposed to disrupt locally and reversibly the BBB to facilitate diffusion of drugs from the micro vasculature into brain tissue. The present study investigates the feasibility and the safety of such an approach in two syngenic mouse models of GBM (GL261 and SMA-560). Local doxorubicin (DOX) concentration in MB-FUS sonicated normal brain tissue as well as in brain tumor tissue was increased as compared to the unsonicated control tissue in the contralateral hemisphere. Moreover, ultrasound mediated BBB disruption, in combination with DOX therapy, resulted in a significant increase of survival and in a slower disease progression in the two syngenic GBM mouse models. In conclusion, our results confirm that MB-ultrasound might ultimately be an effective technology to improve the therapy of GBM, and they provide for the first time evidence that combining MB-FUS with DOX treatment is effective in syngenic mouse models for GBM which can serve as preclinical models to study the impact of immune system on the therapeutic application of MB-FUS chemotherapy. Citation Format: Zsofia Kovaks, Beat Werner, Ernst Martin-Fiori, Michele Bernasconi. Prolonged survival upon ultrasound-enhanced doxorubicin delivery in two syngenic glioblastoma mouse models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-41. doi:10.1158/1538-7445.AM2014-LB-41