Use of a Luciferase-Expressing Orthotopic Rat Brain Tumor Model to Optimize a Targeted Irradiation Strategy for Efficacy Testing with Temozolomide

Alexandra M. Mowday, Natasja G. Lieuwes, Rianne Biemans, Damienne Marcus, Behzad Rezaeifar, Brigitte Reniers, Frank Verhaegen, Jan Theys, Ludwig J. Dubois*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Web of Science)

Abstract

Glioblastoma multiforme (GBM) is a common and aggressive malignant brain cancer with a mean survival time of approximately 15 months after initial diagnosis. Currently, the standard-of-care (SOC) treatment for this disease consists of radiotherapy (RT) with concomitant and adjuvant temozolomide (TMZ). We sought to develop an orthotopic preclinical model of GBM and to optimize a protocol for non-invasive monitoring of tumor growth, allowing for determination of the efficacy of SOC therapy using a targeted RT strategy combined with TMZ. A strong correlation (r = 0.80) was observed between contrast-enhanced (CE)-CT-based volume quantification and bioluminescent (BLI)-integrated image intensity when monitoring tumor growth, allowing for BLI imaging as a substitute for CE-CT. An optimized parallel-opposed single-angle RT beam plan delivered on average 96% of the expected RT dose (20, 30 or 60 Gy) to the tumor. Normal tissue on the ipsilateral and contralateral sides of the brain were spared 84% and 99% of the expected dose, respectively. An increase in median survival time was demonstrated for all SOC regimens compared to untreated controls (average 5.2 days,p<0.05), but treatment was not curative, suggesting the need for novel treatment options to increase therapeutic efficacy.

Original languageEnglish
Article number1585
Number of pages12
JournalCancers
Volume12
Issue number6
DOIs
Publication statusPublished - Jun 2020

Keywords

  • glioblastoma
  • orthotopic models
  • targeted radiotherapy
  • bioluminescence imaging
  • CT imaging
  • temozolomide
  • standard of care
  • INFILTRATING LYMPHOCYTES
  • GLIOBLASTOMA
  • RADIOTHERAPY
  • PROGRESSION
  • HYPOXIA
  • THERAPY
  • CELLS
  • MICE

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