Survival of tumor cells after proton irradiation with ultra-high dose rates

BackgroundLaser acceleration of protons and heavy ions may in the future be used in radiation therapy. Laser-driven particle beams are pulsed and ultra high dose rates of >109 Gy s-1may be achieved. Here we compare the radiobiological effects of pulsed and continuous proton beams.MethodsThe ion microbeam SNAKE at the Munich tandem accelerator was used to directly compare a pulsed and a continuous 20 MeV proton beam, which delivered a dose of 3 Gy to a HeLa cell monolayer within < 1 ns or 100 ms, respectively. Investigated endpoints were G2 phase cell cycle arrest, apoptosis, and colony formation.ResultsAt 10 h after pulsed irradiation, the fraction of G2 cells was significantly lower than after irradiation with the continuous beam, while all other endpoints including colony formation were not significantly different. We determined the relative biological effectiveness (RBE) for pulsed and continuous proton beams relative to x-irradiation as 0.91 ± 0.26 and 0.86 ± 0.33 (mean and SD), respectively.ConclusionsAt the dose rates investigated here, which are expected to correspond to those in radiation therapy using laser-driven particles, the RBE of the pulsed and the (conventional) continuous irradiation mode do not differ significantly.

[1]  J. Wilkens,et al.  Modifying proton fluence spectra to generate spread-out Bragg peaks with laser accelerated proton beams , 2009, Physics in medicine and biology.

[2]  S Svanberg,et al.  Survival of mammalian cells exposed to ultrahigh dose rates from a laser-produced plasma x-ray source. , 1999, Radiology.

[3]  M A Hill,et al.  Is the increased relative biological effectiveness of high LET particles due to spatial or temporal effects? Characterization and OER in V79-4 cells. , 2002, Physics in medicine and biology.

[4]  M. Molls,et al.  Relative biological effectiveness of pulsed and continuous 20 MeV protons for micronucleus induction in 3D human reconstructed skin tissue. , 2010, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[5]  Philippe Lambin,et al.  How costly is particle therapy? Cost analysis of external beam radiotherapy with carbon-ions, protons and photons. , 2010, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[6]  Wolfgang Enghardt,et al.  Dose-dependent biological damage of tumour cells by laser-accelerated proton beams , 2010 .

[7]  E. Hall,et al.  Survival of mammalian cells exposed to x rays at ultra-high dose-rates. , 1969, The British journal of radiology.

[8]  C. Fournier,et al.  Radiation induced cell cycle arrest: an overview of specific effects following high-LET exposure. , 2004, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[9]  Masakatsu Murakami,et al.  Application of laser-accelerated protons to the demonstration of DNA double-strand breaks in human cancer cells , 2009 .

[10]  C. Ling,et al.  Irradiation of cells by single and double pulses of high intensity radiation: oxygen sensitization and diffusion kinetics. , 1976, Current topics in radiation research quarterly.

[11]  Toshiki Tajima,et al.  Laser Acceleration of Ions for Radiation Therapy , 2009 .

[12]  M. Durante,et al.  New challenges in radiobiology research with microbeams , 2011, Radiation and environmental biophysics.

[13]  T. Cremer,et al.  Microirradiation of cells with energetic heavy ions. , 2005, Radiation and environmental biophysics.

[14]  Jan J Wilkens,et al.  Advanced treatment planning methods for efficient radiation therapy with laser accelerated proton and ion beams. , 2010, Medical physics.

[15]  Ryosuke Kodama,et al.  Effects of single-pulse (< or = 1 ps) X-rays from laser-produced plasmas on mammalian cells. , 2004, Journal of radiation research.

[16]  Jose R. Alonso,et al.  What will it take for laser driven proton accelerators to be applied to tumor therapy , 2007 .

[17]  H. Paretzke,et al.  Interaction of ion tracks in spatial and temporal proximity , 2009, Radiation and environmental biophysics.

[18]  Walter Assmann,et al.  Scanning irradiation device for mice in vivo with pulsed and continuous proton beams , 2011, Radiation and environmental biophysics.

[19]  A. Friedl,et al.  No Evidence for a Different RBE between Pulsed and Continuous 20 MeV Protons , 2009, Radiation research.

[20]  H Paganetti,et al.  Significance and Implementation of RBE Variations in Proton Beam Therapy , 2003, Technology in cancer research & treatment.

[21]  R. Berry.  Effects of radiation dose-rate from protracted, continuous irradiation to ultra-high dose-rates from pulsed accelerators. , 1973, British medical bulletin.

[22]  B Shahine,et al.  Particle in cell simulation of laser-accelerated proton beams for radiation therapy. , 2002, Medical physics.

[23]  Marco Durante,et al.  Charged particles in radiation oncology , 2010, Nature Reviews Clinical Oncology.

[24]  Erik Lefebvre,et al.  Practicability of protontherapy using compact laser systems. , 2004, Medical physics.

[25]  Toshiki Tajima,et al.  Laser electron accelerators for radiation medicine: a feasibility study. , 2004, Medical physics.

[26]  J. Cosset,et al.  [Is proton beam therapy the future of radiotherapy? Part I: clinical aspects]. , 2010, Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique.

[27]  A. Friedl,et al.  The Effectiveness of 20 MeV Protons at Nanosecond Pulse Lengths in Producing Chromosome Aberrations in Human-Hamster Hybrid Cells , 2011, Radiation research.

[28]  V Malka,et al.  Exploring ultrashort high-energy electron-induced damage in human carcinoma cells , 2010, Cell Death and Disease.

[29]  R. Hertenberger,et al.  Nanosecond pulsed proton microbeam , 2009 .

[30]  H. Crissman,et al.  Modulation in cell cycle and cyclin B1 expression in irradiated HeLa cells and normal human skin fibroblasts treated with staurosporine and caffeine. , 1997, Experimental cell research.