High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma

Int J Radiat Oncol Biol Phys. 2016 Apr 1;94(5):1173-80. doi: 10.1016/j.ijrobp.2015.12.367. Epub 2015 Dec 29.


Purpose: To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)-pericyte interaction as a potential target for combined treatment with antiangiogenic agents.

Methods and materials: The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed.

Results: HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis of tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours.

Conclusions: HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiography / methods
  • Animals
  • Apoptosis
  • Cell Communication
  • Cell Line, Tumor
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / radiation effects
  • Heterografts
  • Humans
  • Lectins
  • Mice, Nude
  • Neuroblastoma / blood supply
  • Neuroblastoma / diagnostic imaging
  • Neuroblastoma / radiotherapy*
  • Pericytes / cytology
  • Pericytes / radiation effects
  • Radiotherapy Dosage
  • Random Allocation
  • Regional Blood Flow / radiation effects*
  • Time Factors
  • Ultrasonography


  • Lectins