SCDT-30. SURGICAL IMPLANTATION OF AN OSMOTIC PUMP FOR CONVECTION ENHANCED DELIVERY INTO DIPG XENOGRAFT MURINE MODELS

Abstract

INTRODUCTION

Diffuse intrinsic pontine gliomas (DIPG) are fatal, high-grade tumors arising in the pons of children. Convection-enhanced delivery (CED) is a method for directly delivering agents into the tumor, bypassing the blood brain barrier. CED can achieve effective long-term continuous administration when connected to an osmotic pump filled with chemotherapeutic agents. Our objective is to optimize the technique for placement of the CED cannula carrying an osmotic pump into the tumor of preclinical DIPG mouse models.

METHODS

Using agarose gel, Evans blue dye (EBD) was injected at various rates to determine area of distribution. Then, an osmotic pump with a capacity to infuse 100ml over 28 days was used in two cohorts of mice. A cannula was stereotactically implanted into the pons in both cohorts and connected to a subcutaneously placed osmotic pump loaded with EBD or DII. The first cohort assessed the feasibility of implantation into the pons. The second cohort was transplanted with murine DIPG cells and allowed to develop pontine tumors before cannula implantation. The EBD/DII signal was evaluated and compared to tumor cell location to assess delivery to targeted site and distribution.

RESULTS

We have established a methodology for surgical implantation of a cannula attached to an osmotic pump into mouse pons, and assessed the distribution of EBD/DII in healthy as well as tumor bearing murine models of DIPG. We also show that CED cannula installation does not affect the overall survival of the mouse.

CONCLUSION

We show that precise pontine delivery of cargo (dye) has optimal distribution within the pons, tissue integrity is not compromised, and more importantly, does not alter overall survival. This technique will serve as a platform for rapid assessment of tumor response to therapeutic agents. An effective agent can then be translated in clinical setting through upcoming clinical trials.