Survival of tumor cells after proton irradiation with ultra-high dose rates

Abstract

BackgroundLaser 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.MethodsThe 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.ResultsAt 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.ConclusionsAt 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.

Biological effectiveness on live cells of laser driven protons at dose rates exceeding 109 Gy/s

“…This is an encouraging result in view of potential future therapeutic use of ultrashort bursts of laser-driven ions, as, in realistic arrangements, proton pulse durations on the cells will be of ns order or more, as employed in the measurements reported here. We note that similar conclusions on independence of survival results from dose rate (although employing a different cell line and protons with different LET) have been very recently reached in experiments employing a pulsed ion microbeam, 23 operating at similar dose rates and pulse durations as in the experiment presented here.…”

The Effectiveness of 20 MeV Protons at Nanosecond Pulse Lengths in Producing Chromosome Aberrations in Human-Hamster Hybrid Cells

“…These data are of high relevance for clinical use of laser-accelerated proton beams. Previous experiments on monolayer and 3D tissue cultures (in vitro) did not provide evidence for significantly altered radiobiological effectiveness in terms of cytogenetic damage or DNA repair (8)(9)(10)(11)(12). The RBE values determined for pulsed and continuous irradiation modes were always comparable to the RBE of 1.1, which is achieved by conventional proton therapy (20).…”

“…With respect to these endpoints no indication for a significantly altered efficiency of pulsed protons compared to a continuous irradiation was observed (8)(9)(10)(11). Further biological experiments were performed using a human skin tissue model to account for the 3D geometry and the cell interaction, again without statistically significant changes in RBE according to dose rate (12).…”

First results on cell irradiation with laser-driven protons on the TARANIS system

“…This is an encouraging result in view of potential future therapeutic use of ultra short bursts of laser-driven ions, as, in realistic arrangements, proton pulse durations on the cells will be of ns order or more, as employed in the measurements reported here. We note that similar conclusions on independence of survival results from dose rate (although employing a different cell line and protons with different LET) have been very recently reached in experiments employing a pulsed ion microbeam [5] and laser-produced beams focused with quadrupole magnets [6], operating at similar dose rates and pulse durations as in the experiment presented here. We believe that, with an optimized set-up, it will be possible in the near future to increase the dose rate deliverable by laser-accelerated protons by a further 2 orders of magnitude, which will allow testing for the emergence of collective effects as predicted in [7].…”