A comparison of X-ray, proton and alpha beam track structures Geant4 very low energy models

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1 A comparison of X-ray, proton and alpha beam track structures Geant4 very low energy models Aimee McNamara 1, Susanna Guatelli 2, Dale Prokopovich 1, Mark Reinhard 1, Anatoly Rosenfeld 2 1. Australian Nuclear Science and Technology Organisation (ANSTO) 2. Centre for Medical Radiation Physics (CMRP), University of Wollongong, Australia

2 Motivation for new dosimetric concepts Lethal damage to cells by ionising radiation is initiated by damage to the DNA molecule in the form of single and double strand breaks (DSBs). Particle track structure and the ionisation cluster distribution are important factors in assessing the biological effects of different radiation fields. Low-energy secondary electrons (< 1 kev) produce ~ 50% of all ionisations Single strand break (SSB) Double strand break (DSB)

3 Motivation for new dosimetric concepts Absorbed dose is insufficient at satisfactory describing radiation damage on nanometer scales and as our knowledge of cellular function grows we need to evaluate the effect of radiation on the DNA level. Experimentally measuring ionisation cluster-size formation in nanometric targets is very challenging and experimental nanodosimetry can benefit from computational simulations.

4 Aim of this investigation Investigate the track structure (down to ~ ev) of ionising radiation, particularly: Low energy X-rays, as those found in microbeam radiation therapy (MRT) and MeV protons found in abundance in the Bragg peak of proton therapy. Alpha particles e.g. targeted alpha therapy Better understanding of the relative biological effectiveness (RBE). Possible to substitute or supplement different therapies.

5 Microbeam Radiation Therapy (MRT) Experimental treatment consisting of an array of microscopic thin x- ray beams with E ~ kev Microbeams are aimed at the tumoral volume, killing cells directly in beam path while sparing cells in between the peaks Lateral dose profile Spiga et al. (2007) Med. Phys Spiga et al. (2007) Med. Phys Brauer-Krisch et al. (2005) Phys. Med. Biol

6 Proton Therapy Proton beams produce distinct depth dose distributions in matter Appropriate selection of a distribution of proton energies can produce a modulated or "spread-out Bragg peak" (SOBP), which can be calculated to coincide with tumors. Proton therapy cost needs to be reduced.

7 Targeted Alpha Therapy Alpha-emitting radionuclides could selectively target cancer cells. Alpha particles have a high energy (3-9 MeV) but a short path length in tissue ~ 0.1 mm. Surrounding healthy cells are spared high doses.

8 Geant4 Very Low Energy Models (Geant4-DNA) Allows the detailed modelling of the track structure of ionsing particles down to ~ev scale Particles: electron, proton, H, alpha, He+, He Processes: elastic scattering, ionisation, excitation, charge increase and decrease. S Chauvie et al. (2007) IEEE Trans. Nucl. Sci S Incerti et al. (2010) Med. Phys

9 Geant4 Simulation Study Monoenergetic x-ray, proton and alpha pencil beams incident on a water cube of dimension 0.4 mm. The ionisation cluster distribution at different distances from the beam axis and at different points along the beam trajectory is determined in nanometric voxels (4 x 2 x 2 nm). Geometric size and shape of DNA molecule is more important than complex shape (Friedland et al. 1998)

10 Geant4 Simulation Study Photons are tracked down to 250 ev using the Geant4 Low Energy package (based on the Livermore evaluated data libraries) Electrons with energy > 10 kev and protons with energy > 10 MeV are transported by Geant4 Low Energy Package Secondary electrons, protons and alphas are transported down to ~ev using the Geant4 very low energy models

11 Photons Rayleigh scattering, Photoelectric effect, Compton scattering, pair production Geant4 Low Energy Physics Package (based on Livermore evaluated data libraries) Electrons, E> 10 KeV Electrons, E < 10 KeV Protons E > 10 MeV Proton E < 10 MeV Ionisation, Bremsstrahlung, multiple scattering Elastic scattering, excitation, ionisation Ionisation (Electronic Stopping Power by Bethe Bloch), multiple scattering, Bremsstrahlung, inelastic and elastic scattering (hadronic processes) Ionisation, excitation, charge decrease Geant4 Low Energy Physics Package (based on Livermore evaluated data libraries) Geant4 Very Low Energy extensions Geant4 Low Energy Physics Package Geant4 Very Low Energy extensions Physics Processes

12 Photon pencil beam: Ionisation distribution 50 kev 100 kev Plane 1 Plane 2 2 Plane x 2 x 53 nm voxels

13 Energy deposition Photon beam Beam r 2 μm 100 kev 50 kev

14 Proton pencil beam: Ionisation distribution 20 MeV 50 MeV Plane 1 Plane 2 Plane 3

15 Energy deposition Proton beam 20 MeV 50 MeV

16 Proton pencil beam (10 4 ): Ionisation distribution 20 MeV 50 MeV

17 Photon and proton beam comparison 100 kev X-rays 20 MeV protons Plane 1 Plane 2 Plane 3

18 Photon and proton beam comparison X-rays: 100 kev Protons: 20 MeV

19 Alpha pencil beam: Ionisation distribution 4 MeV

20 Conclusions Low energy depositions in living cells needs to be further investigated. Nanodosimetric considerations e.g. ionisation cluster distribution important when considering the RBE of ionising radiation. X-ray beams could produce similar ionisation cluster distributions to MeV protons on the nanometer scale for particular values of the incident particle energy and depth ranges within the target.

21 Future work Further investigation into the nanodosimetric properties of x-rays and protons over different ranges of energies and depths. Include probability of DNA repair mechanisms in analysis. Models for free radical damage. Validation of low energy models in liquid water.

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