A narrow microbeam is more effective for tumor growth suppression than a wide microbeam: anin vivostudy using implanted human glioma cells

Atsushi Uyama,Eiji Kohmura,Nobuteru Nariyama,Takeshi Kondoh,Kunio Shinohara,Manabu Fukumoto,Keiji Umetani

doi:10.1107/s090904951101185x

Abstract

The tumoricidal mechanisms of microbeam radiation therapy, and the more recently proposed minibeam radiation therapy, for the treatment of brain tumors are as yet unclear. Moreover, from among the various parameters of beam geometry the impact of changing the beam width is unknown. In this study, suppression of tumor growth in human glioma cells implanted in mice was evaluated experimentally using microbeams of two different widths: a conventional narrow beam (20 µm width, 100 µm center-to-center distance) and a wide beam (100 µm width, 500 µm center-to-center distance). The tumor growth ratio was compared and acute cell death was studied histologically. With cross-planar irradiation, tumor growth was significantly suppressed between days 4 and 28 after 20 µm microbeam irradiation, whereas tumor growth was suppressed, and not significantly so, only between days 4 and 18 after 100 µm microbeam irradiation. Immunohistochemistry using TUNEL staining showed no increase in TUNEL-positive cells with either microbeam at 24 and 72 h post-irradiation. The 20 µm microbeam was found to be more tumoricidal than the 100 µm microbeam, and the effect was not related to apoptotic cell death. The underlying mechanism may be functional tissue deterioration rather than direct cellular damage in the beam path.

Highlights

Microbeam radiation therapy (MRT), which was originally introduced for the treatment of brain tumors by Slatkin et al (1992), uses a parallel array of microbeams, the so-called ‘coplanar microbeam’, composed of high-intensity and highly directional X-rays generated at a synchrotron radiation facility
The implantation site was either brain parenchyma or the flanks near the hind legs. The results of these studies provided clear evidence that MRTwas associated with the suppression of tumor growth (Dilmanian et al, 2003; Miura et al, 2006) and the extension of life of the rodents implanted with tumors (Laissue et al, 1998; Dilmanian et al, 2002; Smilowitz et al, 2006, 2008, 2009a,b; Regnard et al, 2008; Schultke et al, 2008)
We studied the effects of MRT with a greater beam width and center-to-center distance than reported previously in an animal model implanted with U251 human glioma cells

Summary

Introduction

Microbeam radiation therapy (MRT), which was originally introduced for the treatment of brain tumors by Slatkin et al (1992), uses a parallel array of microbeams, the so-called ‘coplanar microbeam’, composed of high-intensity and highly directional X-rays generated at a synchrotron radiation facility. The principle of this treatment is based on the high resistance of normal brain tissue to such irradiation. The results of these studies provided clear evidence that MRTwas associated with the suppression of tumor growth (Dilmanian et al, 2003; Miura et al, 2006) and the extension of life of the rodents implanted with tumors (Laissue et al, 1998; Dilmanian et al, 2002; Smilowitz et al, 2006, 2008, 2009a,b; Regnard et al, 2008; Schultke et al, 2008)

Objectives

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Results