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

Fujisawa H, Genik PC, Kitamura H, Fujimori A, Uesaka M, Kato TA - Radiat Oncol (2013)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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.

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Related in: MedlinePlus

Dose and LET at each depth in water. Open circles represent relative dose of proton (70 MeV) compared to entrance, and closed circles represent LET spectrum of proton. Open triangles represent relative dose of carbon ions (290 MeV/n) compared to entrance, and triangles represent LET spectrum of carbon ions.
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Figure 1: Dose and LET at each depth in water. Open circles represent relative dose of proton (70 MeV) compared to entrance, and closed circles represent LET spectrum of proton. Open triangles represent relative dose of carbon ions (290 MeV/n) compared to entrance, and triangles represent LET spectrum of carbon ions.

Mentions: Hadron irradiations were conducted at the NIRS in Chiba, Japan. Carbon ions were accelerated to 290 MeV/n using the Heavy Ion Medical Accelerator in Chiba (HIMAC) and protons were accelerated to 70 MeV using the NIRS-930 cyclotron delivery port in C-8. Dose rates for carbon ions and protons were set at 1 Gy/min. Monoenergetic 290 MeV/n carbon ions have a LET value of 13 keV/μm on entrance. Monoenergetic 70 MeV protons have a LET value of 1 keV/μm on entrance. Maximum doses of carbon ions and protons were delivered at depths of 14 and 4 cm in water, respectively (Figure 1) [21]. X-ray irradiations were performed using a TITAN irradiator at 200 kVp, 20 mA and 0.5 cm aluminum and copper filters (Shimadzu, Japan), at a dose rate of 1 Gy/min. Gamma-ray irradiations were carried out at a dose rate of 2.5 Gy/min at Colorado State University (Fort Collins, CO, USA) using a 6,000 Ci (nominal activity) 137Cesium sealed source [Model Mark I-68A (SS0056) J.L. Shepherd, San Fernando, CA, USA]. Irradiations were carried out at room temperature.


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

Fujisawa H, Genik PC, Kitamura H, Fujimori A, Uesaka M, Kato TA - Radiat Oncol (2013)

Dose and LET at each depth in water. Open circles represent relative dose of proton (70 MeV) compared to entrance, and closed circles represent LET spectrum of proton. Open triangles represent relative dose of carbon ions (290 MeV/n) compared to entrance, and triangles represent LET spectrum of carbon ions.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643831&req=5

Figure 1: Dose and LET at each depth in water. Open circles represent relative dose of proton (70 MeV) compared to entrance, and closed circles represent LET spectrum of proton. Open triangles represent relative dose of carbon ions (290 MeV/n) compared to entrance, and triangles represent LET spectrum of carbon ions.
Mentions: Hadron irradiations were conducted at the NIRS in Chiba, Japan. Carbon ions were accelerated to 290 MeV/n using the Heavy Ion Medical Accelerator in Chiba (HIMAC) and protons were accelerated to 70 MeV using the NIRS-930 cyclotron delivery port in C-8. Dose rates for carbon ions and protons were set at 1 Gy/min. Monoenergetic 290 MeV/n carbon ions have a LET value of 13 keV/μm on entrance. Monoenergetic 70 MeV protons have a LET value of 1 keV/μm on entrance. Maximum doses of carbon ions and protons were delivered at depths of 14 and 4 cm in water, respectively (Figure 1) [21]. X-ray irradiations were performed using a TITAN irradiator at 200 kVp, 20 mA and 0.5 cm aluminum and copper filters (Shimadzu, Japan), at a dose rate of 1 Gy/min. Gamma-ray irradiations were carried out at a dose rate of 2.5 Gy/min at Colorado State University (Fort Collins, CO, USA) using a 6,000 Ci (nominal activity) 137Cesium sealed source [Model Mark I-68A (SS0056) J.L. Shepherd, San Fernando, CA, USA]. Irradiations were carried out at room temperature.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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.

Show MeSH
Related in: MedlinePlus