Pulsed versus conventional radiation therapy in combination with temozolomide in a murine orthotopic model of glioblastoma multiforme

David Y. Lee, John L. Chunta, Sean S. Park, Jiayi Huang, Alvaro A. Martinez, Inga S. Grills, Sarah A. Krueger, George D. Wilson, Brian Marples

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20 Scopus citations

Abstract

Purpose: To evaluate the efficacy of pulsed low-dose radiation therapy (PLRT) combined with temozolomide (TMZ) as a novel treatment approach for radioresistant glioblastoma multiforme (GBM) in a murine model. Methods and Materials: Orthotopic U87MG hGBM tumors were established in Nu-Foxn1 nu mice and imaged weekly using a small-animal micropositron emission tomography (PET)/computed tomography (CT) system. Tumor volume was determined from contrast-enhanced microCT images and tumor metabolic activity (SUVmax) from the F18-FDG microPET scan. Tumors were irradiated 7 to 10 days after implantation with a total dose of 14 Gy in 7 consecutive days. The daily treatment was given as a single continuous 2-Gy dose (RT) or 10 pulses of 0.2 Gy using an interpulse interval of 3 minutes (PLRT). TMZ (10 mg/kg) was given daily by oral gavage 1 hour before RT. Tumor vascularity and normal brain damage were assessed by immunohistochemistry. Results: Radiation therapy with TMZ resulted in a significant 3- to 4-week tumor growth delay compared with controls, with PLRT+TMZ the most effective. PLRT+TMZ resulted in a larger decline in SUVmax than RT+TMZ. Significant differences in survival were evident. Treatment after PLRT+TMZ was associated with increased vascularization compared with RT+TMZ. Significantly fewer degenerating neurons were seen in normal brain after PLRT+TMZ compared with RT+TMZ. Conclusions: PLRT+TMZ produced superior tumor growth delay and less normal brain damage when compared with RT+TMZ. The differential effect of PLRT on vascularization may confirm new treatment avenues for GBM.

Original languageEnglish (US)
Pages (from-to)978-985
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume86
Issue number5
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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