A radiobiological study of carbon ions of different linear energy transfer in resistant human malignant cell lines

Abstract

Purpose

Analysis of elimination of four human radioresistant malignant cell lines to mono-energetic and non mono-energetic incoming carbon ion beams, characterized by different linear energy transfer (LET) qualities is performed. Comparisons with protons from the middle of the therapeutic spread out Bragg peak (SOBP) and reference γ-rays are also included.

Materials and methods

HTB140 cells were irradiated at five positions, with different LET, along the 62 MeV carbon pristine Bragg peak. To provide reliable reproducibility of irradiations at INFN-LNS, as the carbon Bragg peak is very narrow, precise positioning of samples for desired LET value is complicated. The peak was slightly widened using two ripple filters. After defining irradiation position and LET at the peak itself where cell killing is almost the highest, irradiation position with the same LET value was found within somewhat broadened peak. HTB140, MCF-7, HTB177 and CRL5876 cells were irradiated at the two described positions. Additionally, irradiations in the middle of 62 MeV proton SOBP and reference γ-rays were performed. Doses ranged from 0.5 to 16 Gy. Cell survival and corresponding radiobiological parameters were assessed seven days after irradiations.

Results

When moving irradiation position along the carbon Bragg curve, LET rises from 85 to 747 keV/µm, while surviving fraction at 2 Gy (SF2) for HTB140 cells, falls from 0.72 to 0.57 further rising to 0.73 on the distal fall-off part of the curve. Improved cell radiosensitivity is seen for the doses below 4 Gy. Relative biological effectiveness (RBE) increases from 4.56 to 7.69 and drops to 4.23. Almost the highest cell killing LET, being ∼200 keV/µm, is used to irradiate HTB140, MCF-7, HTB177 and CRL5876 cells within the pristine and slightly broadened Bragg peak. After irradiations with protons of the mid SOBP, carbon ions of the pristine and slightly widened Bragg peak RBE ranges for HTB140 cells from 2.08, 4.81 to 7.06, for MCF-7 from 1.70, 3.28 to 4.17, for HTB177 from 1.98, 4.18 to 5.08 and for CRL5876 from 1.33, 2.57 to 3.51.

Conclusions

Significant elimination of HTB140 cells is observed along the carbon Bragg curve. The highest one is achieved by LET that is at the level of already reported. For the same LET, mono-energetic carbon ions provide higher cell elimination than the non mono-energetic. For all cell lines, both carbon ion beams, more the monoenergetic one, express stronger killing rate than protons and especially γ-rays.

Keywords:

• Mono-energetic and non mono-energetic carbon ions
• protons
• LET
• human malignant radioresistant cells
• survival

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This work was financially supported by the Ministry of Education, Science and Technological Development of Serbia [Grants 173046 and 171019] and by Fondo Affari Internazionali (FAI) of the INFN-LNS. The research leading to these results has also received funding from the European Union Seventh Framework Programme FP7/2010-2014 under Grant Agreement No. 262010 – ENSAR and HORIZIN2020 Research and Innovation Program under Grant Agreement No. 654002 – ENSAR2. The EC is not liable for any use that can be made on the information contained herein.

Notes on contributors

Ivan M. Petrović

Ivan M. Petrović received his Ph.D. in nuclear physics from the University of Paris XI – South (Orsay), France. He is a Research Professor in the Department of Physics at the Vinča Institute of Nuclear Sciences of the University of Belgrade, Serbia, and is actively involved in research and teaching.

Aleksandra M. Ristić Fira

Aleksandra M. Ristić Fira received her Ph.D. in molecular biology from the University of Belgrade, Faculty of Biology. She is a Research Professor at the University of Belgrade, Vinča Institute of Nuclear Sciences. She is head of Laboratory of radiation biology and is actually engaged in teaching and research.

Otilija D. Keta

Otilija D. Keta received her Ph.D. from the University of Belgrade, Faculty of Biology. Presently, she is engaged as Research Assistant Professor at the Vinča Institute of Nuclear Sciences of the University of Belgrade.

Vladana D. Petković

Vladana D. Petković received her Master degree from the University of Belgrade, Faculty of Biology. She is a Ph.D. student at the University of Belgrade, Faculty of Biology, working on her thesis at the Vinča Institute of Nuclear Sciences of the University of Belgrade.

Giada Petringa

Giada Petringa received her Ph.D. in Physics from the University of Catania(I). She is an expert in diagnostics and dosimetry for clinical and laser-driven proton/ions beams. She has a large experience in Monte Carlo simulations and she is a member of the Geant4 international collaboration.

Pablo Cirrone

Pablo Cirrone received his PhD in Physics at the University of Catania(I). He is a senior researcher at the INFN Italian institute for nuclear physics and professor of the ‘Medical Physics’ class at the Catania University. He is an expert of Hadrontherapy, laser-driven acceleration and diagnostic, dosimetry of ionization radiation and Monte Carlo simulations.

Giacomo Cuttone

Giacomo Cuttone is Research Director at the INFN Italian institute for nuclear physics and professor of the ‘Accelerator Physic’ class at the Catania University. He is also the former Director of INFN-LNS. He is expert of accelerator physics, hadrontherapy and dosimetry for ionizing radiation.