Survival of tumor cells after proton irradiation with ultra-high dose rates
Tóm tắt
Laser 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.
The 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.
At 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.
At 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.
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Tài liệu tham khảo
Bouyon-Monteau A, Habrand JL, Datchary J, Alapetite C, Bolle S, Dendale R, Feuvret L, Helfre S, Calugaru V, Cosset JM, Bey P: [Is proton beam therapy the future of radiotherapy? Part I: clinical aspects] (French). Cancer Radiother 2010,14(8):727-738.
Durante M, Loeffler JS: Charged particles in radiation oncology. Nat Rev Clin Oncol 2010,7(1):37-43. 10.1038/nrclinonc.2009.183
Peeters A, Grutters JP, Pijls-Johannesma M, Reimoser S, De Ruysscher D, Severens JL, Joore MA, Lambin P: How costly is particle therapy? Cost analysis of external beam radiotherapy with carbon-ions, protons and photons. Radiother Oncol 2010,95(1):45-53. 10.1016/j.radonc.2009.12.002
Fourkal E, Shahine B, Ding M, Li JS, Tajima T, Ma CM: Particle in cell simulation of laser-accelerated proton beams for radiation therapy. Med Phys 2002,29(12):2788-2798. 10.1118/1.1521122
Malka V, Fritzler S, Lefebvre E, d'Humières E, Ferrand R, Grillon G, Albaret C, Meyroneinc S, Chambaret JP, Antonetti A, Hulin D: Practicability of protontherapy using compact laser systems. Med Phys 2004,31(6):1587-1592. 10.1118/1.1747751
Chiu C, Fomytskyi M, Grigsby F, Raischel F, Downer MC, Tajima T: Laser electron accelerators for radiation medicine: a feasibility study. Med Phys 2004,31(7):2042-2052. 10.1118/1.1739301
Linz U, Alonso J: What will it take for laser driven proton accelerators to be applied to tumor therapy? Phys Rev ST Accel Beams 2007, 10: 094801.
Schell S, Wilkens JJ: Modifying proton fluence spectra to generate spread-out Bragg peaks with laser accelerated proton beams. Phys Med Biol 2009,54(19):N459-466. 10.1088/0031-9155/54/19/N04
Schell S, Wilkens JJ: Advanced treatment planning methods for efficient radiation therapy with laser accelerated proton and ion beams. Med Phys 2010,37(10):5330-5340. 10.1118/1.3491406
Tajima T, Habs D, Yan X: Laser Acceleration of Ions for Radiation Therapy. Reviews of Accelerator Science and Technology 2009, 2: 201-228. 10.1142/S1793626809000296
Dollinger G, Bergmaier A, Hable V, Hertenberger R, Greubel C, Hauptner A, Reichart P: Nanosecond pulsed proton microbeam. Nucl Instr and Meth B 2009, 267: 2008-2012. 10.1016/j.nimb.2009.03.006
Epp ER, Weiss H, Ling CC: Irradiation of cells by single and double pulses of high intensity radiation: Oxygen sensitization and diffusion kinetics. Curr Top Radiat Res Q 1976, 11: 201-250.
Berry RJ: Effects of radiation dose-rate. From protracted, continuous irradiation to ultra high dose-rates from pulsed accelerators. Br Med Bull 1973,29(1):44-47.
Berry RJ, Hall EJ, Forster DW, Storr TH, Goodman MJ: Survival of mammalian cells exposed to x-rays at ultra-high dose-rates. Br J Radiol 1969, 42: 102-107. 10.1259/0007-1285-42-494-102
Tillman C, Grafström G, Jonsson AC, Jönsson BA, Mercer I, Mattsson S, Strand SE, Svanberg S: Survival of mammalian cells exposed to ultrahigh dose rates from a laser-produced plasma x-ray source. Radiology 1999,213(3):860-865.
Shinohara K, Nakano H, Miyazaki N, Tago M, Kodama R: Effects of single-pulse (< or = 1 ps) X-rays from laser-produced plasmas on mammalian cells. J Radiat Res (Tokyo) 2004,45(4):509-514. 10.1269/jrr.45.509
Hill MA, Stevens DL, Marsden SJ, Allot R, Turcu IC, Goodhead DT: Is the increased relative biological effectiveness of high LET particles due to spatial or temporal effects? Characterization and OER in V79-4 cells. Phys Med Biol 2002,47(19):3543-3555. 10.1088/0031-9155/47/19/308
Yogo A, Sato K, Nishikino M, Mori M, Teshima T, Numasaki H, Murakami M, et al.: Application of laser-accelerated protons to the demonstration of DNA double-strand breaks in human cancer cells. Appl Phys Lett 2009, 94: 181502. 10.1063/1.3126452
Kraft SD, Richter C, Zeil K, Baumann M, Beyreuther E, Bock S, Bussmann M, Cowan TE, Dammene Y, Enghardt W, Helbig U, Karsch L, Kluge T, Laschinsky L, Lessmann E, Metzkes J, Naumburger D, Sauerbrey R, Schürer M, Sobiella M, Woithe J, Schramm U, Pawelke J: Dose-dependent biological damage of tumour cells by laser-accelerated proton beams Focus on Laser- and Beam-Driven Plasma Accelerators. New J Phys 2010, 12: 085003. 10.1088/1367-2630/12/8/085003
Rigaud O, Fortunel NO, Vaigot P, Cadio E, Martin MT, Lundh O, Faure J, Rechatin C, Malka V, Gauduel YA: Exploring ultrashort high-energy electron-induced damage in human carcinoma cells. Cell Death Disease 2010, 1: e73. 10.1038/cddis.2010.46
Schmid TE, Dollinger G, Hauptner A, Hable V, Greubel C, Auer S, Friedl AA, Molls M, Röper B: No evidence for a different RBE between pulsed and continuous 20 MeV protons. Radiat Res 2009,172(5):567-574. 10.1667/RR1539.1
Schmid TE, Dollinger G, Hable V, Greubel C, Zlobinskaya O, Michalski D, Molls M, Röper B: Relative biological effectiveness of pulsed and continuous 20 MeV protons for micronucleus induction in 3D human reconstructed skin tissue. Radiother Oncol 2010,95(1):66-72. 10.1016/j.radonc.2010.03.010
Schmid TE, Dollinger G, Hable V, Greubel C, Zlobinskaya O, Michalski D, Auer S, Friedl AA, Schmid E, Molls M, Röper B: The Effectiveness of 20 MeV Protons at Nanosecond Pulse Lengths in Producing Chromosome Aberrations in Human-Hamster Hybrid Cells. Radiat Res 2011,175(6):719-727. 10.1667/RR2465.1
Hauptner A, Dietzel S, Drexler GA, Reichart P, Krücken R, Cremer T, Friedl AA, Dollinger G: Microirradiation of cells with energetic heavy ions. Radiat Environ Biophys 2004,42(4):237-245. 10.1007/s00411-003-0222-7
Narayanan PK, Rudnick JM, Walthers EA, Crissman HA: Modulation in cell cycle and cyclin B1 expression in irradiated HeLa cells and normal human skin fibroblasts treated with staurosporine and caffeine. Exp Cell Res 1997,233(1):118-127. 10.1006/excr.1997.3549
Kreipl MS, Friedland W, Paretzke HG: Interaction of ion tracks in spatial and temporal proximity. Radiat Environ Biophys 2009,48(4):349-359. 10.1007/s00411-009-0234-z
Fournier C, Taucher-Scholz G: Radiation induced cell cycle arrest: an overview of specific effects following high-LET exposure. Radiother Oncol 2004,73(Suppl 2):S119-122.
Paganetti H: Significance and implementation of RBE variations in proton beam therapy. Technol Cancer Res Treat 2003,2(5):413-426.
Durante M, Friedl AA: New challenges in radiobiology research with microbeams. Radiat Environ Biophys 2011,50(3):335-338. 10.1007/s00411-011-0373-x
Greubel C, Assmann W, Burgdorf C, Dollinger G, Du G, Hable V, Hapfelmeier A, Hertenberger R, Kneschaurek P, Michalski D, Molls M, Reinhardt S, Röper B, Schell S, Schmid TE, Siebenwirth C, Wenzl T, Zlobinskaya O, Wilkens JJ: Scanning irradiation device for mice in vivo with pulsed and continuous proton beams. Radiat Environ Biophys 2011,50(3):339-344. 10.1007/s00411-011-0365-x