Relative biological effectiveness of pulsed and continuous 20MeV protons for micronucleus induction in 3D human reconstructed skin tissue

Schmid, Thomas E.; Dollinger, Günther; Hable, Volker; Greubel, Christoph; Zlobinskaya, Olga; Michalski, Dörte; Molls, Michael; Röper, Barbara

doi:10.1016/j.radonc.2010.03.010

« Previous Next »Radiotherapy & Oncology
Volume 95, Issue 1 , Pages 66-72, April 2010

Relative biological effectiveness of pulsed and continuous 20MeV protons for micronucleus induction in 3D human reconstructed skin tissue

Thomas E. Schmid
- Department of Radiation Oncology, Technische Universitaet Muenchen, Germany
- Corresponding author at: Klinikum rechts der Isar der Technischen Universität München, Klinik für Strahlentherapie und radiologische Onkologie Ismaningerstr. 22, 81675 München, Germany.
Günther Dollinger
- Institute for Applied Physics and Metrology, Universitaet der Bundeswehr Muenchen, Neubiberg, Germany
Volker Hable
- Institute for Applied Physics and Metrology, Universitaet der Bundeswehr Muenchen, Neubiberg, Germany
Christoph Greubel
- Institute for Applied Physics and Metrology, Universitaet der Bundeswehr Muenchen, Neubiberg, Germany
Olga Zlobinskaya
- Department of Radiation Oncology, Technische Universitaet Muenchen, Germany
Dörte Michalski
- Department of Radiation Oncology, Technische Universitaet Muenchen, Germany
Michael Molls
- Department of Radiation Oncology, Technische Universitaet Muenchen, Germany
Barbara Röper
- Department of Radiation Oncology, Technische Universitaet Muenchen, Germany

Received 22 December 2009; received in revised form 25 February 2010; accepted 7 March 2010. published online 29 March 2010.

Abstract

Background and purpose

Laser accelerated radiotherapy is a prospect for cancer treatment with proton and/or carbon ion beams that is currently under fast development. In principal, ultra fast, high-energy laser pulses will lead to a “pulsed” delivery of the induced ion beam with pulse durations of 1ns and below, whereas conventional proton beams deriving from a cyclotron or synchrotron apply the dose within 100ms (“continuous”).

Materials and methods

A simulation of both irradiation modes could be established at the Munich tandem accelerator with a 20MeV proton beam, and a wide-field fast scanning system was implemented that allowed for application of up to 5Gy per tissue voxel in a single pulse. The relative biological effectiveness (RBE) of pulsed and continuous modes of irradiation with 20MeV protons relative to the reference radiation 70kV X-rays was examined in a human tissue model (3D human reconstructed skin, EpiDermFT™) which preserves the three-dimensional geometric arrangement and communication of cells present in tissues in vivo. Using the induction of micronuclei (MN) in keratinocytes as the biological endpoint, the RBE was calculated as the ratio between the dose of 70kV X-rays and 3Gy of 20MeV protons (pulsed or continuous) which produced equal response.

Results

For pulsed and continuous 20MV proton exposures of the human skin model, RBE values of 1.08±0.20 and 1.22±0.15 versus 70kV X-rays were obtained in a first experiment and 1.00±0.14 and 1.13±0.14 in a second experiment during distinct beam access times, respectively. The ∼10% difference in RBE between the respective irradiation modes in both experiments was associated with large uncertainties which were not statistically significant (p≈0.5).

Conclusion

These findings represent an important step on the way towards application of laser-accelerated protons for clinical radiotherapy. Further clinically relevant endpoints in normal and tumor tissue have to be evaluated.

Keywords: Protons, Pulsed irradiation, RBE, In vitro tissue, Micronucleus assay