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Open Access Research

Comparison of human chordoma cell-kill for 290 MeV/n carbon ions versus 70 MeV protons in vitro

Hiroshi Fujisawa1, Paula C Genik2, Hisashi Kitamura3, Akira Fujimori4, Mitsuru Uesaka1 and Takamitsu A Kato2*

Author Affiliations

1 Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8656, Japan

2 Department of Environmental & Radiological Health Sciences, Colorado State University, 1618 Campus Delivery, Fort Collins, CO, 80523, USA

3 Research Development and Support Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba, 263-8555, Japan

4 Research Center for Charged Particle Therapy, Molecular Target Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba, 263-8555, Japan

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Radiation Oncology 2013, 8:91  doi:10.1186/1748-717X-8-91

Published: 15 April 2013

Abstract

Background

While the pace of commissioning of new charged particle radiation therapy facilities is accelerating worldwide, biological data pertaining to chordomas, theoretically and clinically optimally suited targets for particle radiotherapy, are still lacking. In spite of the numerous clinical reports of successful treatment of these malignancies with this modality, the characterization of this malignancy remains hampered by its characteristic slow cell growth, particularly in vitro.

Methods

Cellular lethality of U-CH1-N cells in response to different qualities of radiation was compared with immediate plating after radiation or as previously reported using the multilayered OptiCell™ system. The OptiCell™ system was used to evaluate cellular lethality over a broad dose-depth deposition range of particle radiation to anatomically mimic the clinical setting. Cells were irradiated with either 290 MeV/n accelerated carbon ions or 70 MeV accelerated protons and photons and evaluated through colony formation assays at a single position or at each depth, depending on the system.

Results

There was a cell killing of approximately 20–40% for all radiation qualities in the OptiCell™ system in which chordoma cells are herein described as more radiation sensitive than regular colony formation assay. The relative biological effectiveness values were, however, similar in both in vitro systems for any given radiation quality. Relative biological effectiveness values of proton was 0.89, of 13–20 keV/μm carbon ions was 0.85, of 20–30 keV/μm carbon ions was 1.27, and >30 keV/μm carbon ions was 1.69. Carbon-ions killed cells depending on both the dose and the LET, while protons depended on the dose alone in the condition of our study. This is the first report and characterization of a direct comparison between the effects of charged particle carbon ions versus protons for a chordoma cell line in vitro. Our results support a potentially superior therapeutic value of carbon particle irradiation in chordoma patients.

Conclusion

Carbon ion therapy may have an advantage for chordoma radiotherapy because of higher cell-killing effect with high LET doses from biological observation in this study.

Keywords:
Particle radiotherapy; Chordoma; OptiCell™; High LET; Carbon; Proton; Bragg peak