Synchrotron microbeam radiation therapy induces hypoxia in intracerebral gliosarcoma but not in the normal brain

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• 作者：Audrey Bouchet ; Benjamin Lemasson ; Thomas Christen ; Marine Potez ; Claire Rome ; Nicolas Coquery ; C¨¦line Le Clec¡¯h ; Anaick Moisan ; Elke Br?uer-Krisch ; G¨¦raldine Leduc ; Chantal R¨¦my ; Jean A. Laissue ; Emmanuel L. Barbier ; Emmanuel Brun ; Rapha?l Serduc
• 关键词：Synchrotron microbeam radiation therapy ; Brain tumors ; Oxygen saturation ; Vessel radiation responses ; MRI ; Rat
• 刊名：Radiotherapy and Oncology
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：108
• 期：1
• 页码：143-148
• 全文大小：1217 K

文摘

Purpose

Synchrotron microbeam radiation therapy (MRT) is an innovative irradiation modality based on spatial fractionation of a high-dose X-ray beam into lattices of microbeams. The increase in lifespan of brain tumor-bearing rats is associated with vascular damage but the physiological consequences of MRT on blood vessels have not been described. In this manuscript, we evaluate the oxygenation changes induced by MRT in an intracerebral 9L gliosarcoma model.

Methods

Tissue responses to MRT (two orthogonal arrays (2 ¡Á 400 Gy)) were studied using magnetic resonance-based measurements of local blood oxygen saturation (MR_SO₂) and quantitative immunohistology of RECA-1, Type-IV collagen and GLUT-1, marker of hypoxia.

Results

In tumors, MR_SO₂ decreased by a factor of 2 in tumor between day 8 and day 45 after MRT. This correlated with tumor vascular remodeling, i.e. decrease in vessel density, increases in half-vessel distances (¡Á5) and GLUT-1 immunoreactivity. Conversely, MRT did not change normal brain MR_SO₂, although vessel inter-distances increased slightly.

Conclusion

We provide new evidence for the differential effect of MRT on tumor vasculature, an effect that leads to tumor hypoxia. As hypothesized formerly, the vasculature of the normal brain exposed to MRT remains sufficiently perfused to prevent any hypoxia.