Can anti-vascular endothelial growth factor antibody reverse radiation necrosis? A preclinical investigation

Chong Duan, Carlos J. Perez-Torres, Liya Yuan, John A. Engelbach, Scott C. Beeman, Christina I. Tsien, Keith M. Rich, Robert E. Schmidt, Joseph J.H. Ackerman, Joel R. Garbow

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Anti-vascular endothelial growth factor (anti-VEGF) antibodies are a promising new treatment for late time-to-onset radiation-induced necrosis (RN). We sought to evaluate and validate the response to anti-VEGF antibody in a mouse model of RN. Mice were irradiated with the Leksell Gamma Knife Perfexion™ and then treated with anti-VEGF antibody, beginning at post-irradiation (PIR) week 8. RN progression was monitored via anatomic and diffusion MRI from weeks 4–12 PIR. Standard histology, using haematoxylin and eosin (H&E), and immunohistochemistry staining were used to validate the response to treatment. After treatment, both post-contrast T1-weighted and T2-weighted image-derived lesion volumes decreased (P < 0.001), while the lesion volumes for the control group increased. The abnormally high apparent diffusion coefficient (ADC) for RN also returned to the ADC range for normal brain following treatment (P < 0.001). However, typical RN pathology was still present histologically. Large areas of focal calcification were observed in ~50% of treated mouse brains. Additionally, VEGF and hypoxia-inducible factor 1-alpha (HIF-1α) were continually upregulated in both the anti-VEGF and control groups. Despite improvements observed radiographically following anti-VEGF treatment, lesions were not completely resolved histologically. The subsequent calcification and the continued upregulation of VEGF and HIF-1α merit further preclinical/clinical investigation.

Original languageEnglish (US)
Pages (from-to)9-16
Number of pages8
JournalJournal of Neuro-Oncology
Volume133
Issue number1
DOIs
StatePublished - May 1 2017
Externally publishedYes

Keywords

  • Bevacizumab
  • Calcification
  • Diffusion
  • HIF-1α
  • Radiation necrosis
  • VEGF

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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