Dose-controlled irradiation of cancer cells with laser-accelerated proton pulses

Proton beams are a promising tool for the improvement of radiotherapy of cancer, and compact laser-driven proton radiation (LDPR) is discussed as an alternative to established large-scale technology facilitating wider clinical use. Yet, clinical use of LDPR requires substantial development in reliable beam generation and transport, but also in dosimetric protocols as well as validation in radiobiological studies. Here, we present the first dose-controlled direct comparison of the radiobiological effectiveness of intense proton pulses from a laser-driven accelerator with conventionally generated continuous proton beams, demonstrating a first milestone in translational research. Controlled dose delivery, precisely online and offline monitored for each out of ∼4,000 pulses, resulted in an unprecedented relative dose uncertainty of below 10 %, using approaches scalable to the next translational step toward radiotherapy application.

[1]  Christian Richter,et al.  Preparation of laser-accelerated proton beams for radiobiological applications , 2011 .

[2]  A. V. Kuznetsov,et al.  Oncological hadrontherapy with laser ion accelerators , 2002 .

[3]  B. Beuthien-Baumann,et al.  Prediction of clonogenic cell survival curves based on the number of residual DNA double strand breaks measured by γH2AX staining , 2009, International journal of radiation biology.

[4]  Giuseppe Schettino,et al.  Biological effectiveness on live cells of laser driven protons at dose rates exceeding 109 Gy/s , 2012 .

[5]  D Kiefer,et al.  Radiation-pressure acceleration of ion beams driven by circularly polarized laser pulses. , 2009, Physical review letters.

[6]  U. Schramm,et al.  Direct observation of prompt pre-thermal laser ion sheath acceleration , 2012, Nature Communications.

[7]  Masakatsu Murakami,et al.  Measurement of relative biological effectiveness of protons in human cancer cells using a laser-driven quasimonoenergetic proton beamline , 2011 .

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

[9]  Mayer Ramona,et al.  Epidemiological aspects of hadron therapy: A prospective nationwide study of the Austrian project MedAustron and the Austrian Society of Radiooncology (OEGRO) , 2004 .

[10]  M. Molls,et al.  Induction and repair of DNA double-strand breaks assessed by gamma-H2AX foci after irradiation with pulsed or continuous proton beams , 2012, Radiation and environmental biophysics.

[11]  R. P. Singhal,et al.  Applications for Nuclear Phenomena Generated by Ultra-Intense Lasers , 2003, Science.

[12]  C. Richter,et al.  [Experimental investigation of the collection efficiency of a PTW Roos ionization chamber irradiated with pulsed beams at high pulse dose with different pulse lengths]. , 2011, Zeitschrift fur medizinische Physik.

[13]  Kenneth W. D. Ledingham,et al.  Laser-driven particle and photon beams and some applications , 2010 .

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

[15]  Michael Bussmann,et al.  Laser accelerated protons captured and transported by a pulse power solenoid , 2011 .

[16]  E. Rogakou,et al.  DNA Double-stranded Breaks Induce Histone H2AX Phosphorylation on Serine 139* , 1998, The Journal of Biological Chemistry.

[17]  Deanna M. Pennington,et al.  Energetic proton generation in ultra-intense laser–solid interactions , 2000 .

[18]  D. Neely,et al.  Proton acceleration using 50 fs, high intensity ASTRA-Gemini laser pulses , 2011 .

[19]  Kiminori Kondo,et al.  Proton acceleration to 40 MeV using a high intensity, high contrast optical parametric chirped-pulse amplification/Ti:sapphire hybrid laser system. , 2012, Optics letters.

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

[21]  P. Pommier,et al.  A "one-day survey": as a reliable estimation of the potential recruitment for proton- and carbon- ion therapy in France. , 2004, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[22]  Dieter Schardt,et al.  Heavy-ion tumor therapy: Physical and radiobiological benefits , 2010 .

[23]  Wei Luo,et al.  Development of a laser-driven proton accelerator for cancer therapy , 2006 .

[24]  M. Krause,et al.  The extreme radiosensitivity of the squamous cell carcinoma SKX is due to a defect in double-strand break repair. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[25]  I. Tannock,et al.  The translational research chain: is it delivering the goods? , 2001, International journal of radiation oncology, biology, physics.

[26]  G. Petrov,et al.  Control of energy spread and dark current in proton and ion beams generated in high-contrast laser solid interactions. , 2011, Physical review letters.

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

[28]  O Willi,et al.  Hot electrons transverse refluxing in ultraintense laser-solid interactions. , 2010, Physical review letters.

[29]  J. Pawelke,et al.  DNA double-strand break signalling: X-ray energy dependence of residual co-localised foci of γ-H2AX and 53BP1 , 2009, International journal of radiation biology.

[30]  K. A. Flippo,et al.  Increased laser-accelerated proton energies via direct laser-light-pressure acceleration of electrons in microcone targetsa) , 2011 .

[31]  C. Richter,et al.  A dosimetric system for quantitative cell irradiation experiments with laser-accelerated protons , 2011, Physics in medicine and biology.

[32]  S. V. Bulanov,et al.  Feasibility of using laser ion accelerators in proton therapy , 2002 .

[33]  G I Dudnikova,et al.  Monoenergetic proton beams accelerated by a radiation pressure driven shock. , 2010, Physical review letters.

[34]  M Silari,et al.  Proton beam dosimetry: a comparison between the Faraday cup and an ionization chamber. , 1997, Physics in medicine and biology.

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

[36]  Michael Bussmann,et al.  The scaling of proton energies in ultrashort pulse laser plasma acceleration , 2010 .

[37]  Junjie Chen,et al.  Tumor Suppressor P53 Binding Protein 1 (53bp1) Is Involved in DNA Damage–Signaling Pathways , 2001, The Journal of cell biology.

[38]  J S Li,et al.  Particle selection for laser-accelerated proton therapy feasibility study. , 2003, Medical physics.

[39]  Wolfgang Enghardt,et al.  Radiobiological effectiveness of laser accelerated electrons in comparison to electron beams from a conventional linear accelerator. , 2012, Journal of radiation research.