Relative Biological Effectiveness of Single-Shot Irradiation With Laser-Driven Nanosecond Proton Bunches

Abstract

Owing to their superior depth-dose curve, protons are a favorable choice in radiation therapy. High intensity table-top lasers are a proposed mechanism of reducing the cost and space consumed by conventional means of proton acceleration. However, before clinical application of laser-driven protons can be considered, cell experiments with laser-driven beams constitute an important preliminary step to demonstrate the increasing maturity of this technology. Here we present first biological results of single-shot irradiation with laser-driven nanosecond proton bunches. The ATLAS Ti-Sapphire laser delivered 400 mJ in a 30 fs pulse on a diamond-like Carbon target for proton acceleration. Two mini-quadrupole magnets focused the protons over a distance of 1.2 m and acted as an energy filter to produce a quasi-monoenergetic beam with an energy of 5.3 ± 0.15 MeV. The beam manifested as a line focus of ∼0.5 mm in width and 6 mm in length. This was used to irradiate human tumor cells over a dose range of 0.13 to 7 Gy, realized by single laser shots. Due to the inhomogeneous dose distribution across the line focus, full dose response curves for single, nanosecond proton bunches were obtained for each irradiated sample. For obtaining a reference dose-response curve cells were irradiated at the Munich tandem accelerator with the same proton energy using a delivery mode where the radiation was given within 100 ms. For all experiments, HeLa cells were seeded directly onto the cell holder window composed of 6 μm Mylar foil 48 hours prior to irradiation. Cells were fixed 30 minutes after irradiation and stained using Alexa 488 for 53bp1 and Cy3 for γ-H2AX foci. Dose was measured using radiochromic film (Gafchromic EBT2) placed immediately behind the back layer of the cell holder. Foci (γ-H2AX and 53bp1) were counted after irradiation with laser-driven protons and with protons from the conventional accelerator. An RBE of 1.3 ± 0.3 relative to 200 kV X-rays was determined for the induction of γ-H2AX foci and also for 53bp1 foci for laser-driven protons. These results indicate no substantial difference between laser-driven proton beams and those produced by conventional acceleration means. The RBE obtained in this study for laser-driven protons is in agreement with RBE values in conventional beams at comparable proton energies. This indicates that no new radiobiological effects are to be expected with nanosecond proton delivery, in line with previous studies in single, nanosecond proton bunches at conventional sources. This confirms that for future applications in radiation therapy, the same RBE as for conventional sources can be assumed.