824 Development of a Preclinical Glioblastoma Platform in a Murine Model in order to optimize Diffusion Kurtosis Imaging Protocol to be able to accurately differentiate Acute and Chronic Radiation Necrosis from Tumor Recurrence

Abstract

INTRODUCTION: Radiation induced damage in glioblastoma (GB) patients can present in a late-delayed fashion as radiation necrosis (RN) or tumor recurrence (TR). The radiographic differentiation of these entities is particularly challenging as they appear similar on magnetic resonance imaging (MRI.) Failure to differentiate these can ultimately lead to unnecessary surgery and early cessation radiation therapy. There is a need for developing novel non-invasive techniques that can reliably distinguish between radiation necrosis and tumor recurrence. METHODS: We orthotopically transplanted GL261 mouse glioblastoma cells into C57BL/6 mice, with successful tumor induction verified by MRI after two weeks. To consistently induce RN/TR, an aggressive radiation dose fractionation (12 Gy/60 Gy) on alternating days was used. This was completed such that one portion of the tumor received 100% dose of radiation fraction, sufficient to cause RN, whereas the tumor edge received only 50% of the dose, allowing for tumor recurrence. At four time points, MRI and diffusion kurtosis imaging (DKI) were obtained, and objective metrics such as mean, axial, and radial kurtosis and diffusivity were calculated. RESULTS: Our data demonstrated mice tumor recurrence and radiation necrosis on MR imaging. MRI and DKI at 2 weeks following orthotopic glioblastoma implantation demonstrated edema and gyral edema compatible with tumor recurrence. One week later, imaging sequences demonstrated continued tumor progression. This demonstrated that our proposed model for radiation induction was effective at achieving its goal of creating some areas of RN and some of TR. CONCLUSIONS: Our results provides an invaluable platform for the mechanistic study of acute radiation necrosis, chronic radiation necrosis, and tumor recurrence, and management of these conditions.