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

作者：Jani Ashish; Shaikh Fauzia; Barton Sunjay; Willis Callen; Banerjee Debarshi; Mitchell Jason; Hernandez Sonia L; Hei Tom; Kadenhe Chiweshe Angela; Yamashiro Darrell J; Connolly Eileen P^*

来源：International Journal of Radiation Oncology, Biology, Physics, 2016, 94(5): 1173-1180.

DOI：10.1016/j.ijrobp.2015.12.367

Purpose: To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC) epericyte 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.

• 出版日期2016-4-1