In radiotherapy of tumours hadrons exhibit some physical and potentially biological advantages over photons like a favourable dose distribution and, in case of carbon ions, less dependency of cell cycle distribution or tissue oxygenation. Due to building and cost requirements so far the availability of ion beam radiotherapy is limited. Laser-generated ion beams might be a more space- and cost-effective alternative. Thus, we aim to explore the radiobiological aspects of laser-generated particle irradiation. In case of protons, the impact of such a pulsed beam on cells or tissues is unclear, as the temporal dose delivery is expected to differ from current radiotherapy modalities by several orders of magnitude. To prepare its clinical use, we explore the relative biological effectiveness of protons with nanosecond pulses in comparison with continuous proton irradiation, starting with cell experiments and moving on to tissues and xenograft tumors in animals.

Since laser accelerated proton beams are not yet available we explored the RBE of pulsed versus continuous proton irradiation using SNAKE (Superconducting Nanoprobe for Applied nuclear [Kern] physics Experiments) microprobe of the Munich tandem accelerator during the last three years. A newly developed beam preparation scheme at SNAKE results in pulsed (less than 1 nanosecond) proton beams of 23 MeV which are similar to those expected from laser acceleration where a certain portion of a tumour will be irradiated by a single proton pulse. It can directly be compared to a continuous beam irradiation at SNAKE reducing potential systematic errors. We did not find evidence for significant differences in RBE in single experiments, which supports the idea that the amount of genetic damage inflicted is not markedly affected by the ultrahigh dose-rate of a pulsed delivery mode. However, the results of all 10 independently performed experiments together hint at a slightly higher RBE after continuous compared to pulsed irradiation mode. From our preliminary observations and those of our collaborators in project D.3.2, we estimate that differences will be small, if present.

In February 2010 we started to measure the effectiveness of pulsed particle beams in treatment of cancer-infected nude mice, using a large field pulsed proton beam at the Munich tandem accelerator (23 MeV for treatment to tissue depths up to 4 mm). Our first experiment was a growth delay experiment with a single proton dose of 20 Gy in pulsed versus continuous mode. Strong collaborations are in place with project D.3.1 for dosimetry and with the junior Research Group “Advanced Technologies in Radiation Therapy” for dose calculations. The first in-vivo results from the growth delay experiments are needed to determine if a TCD50 (50 % tumour control dose) experiment is necessary to answer the questions whether intense ultra-short ion pulses will lead to different RBE in tumour tissue in-vivo.
Subsequently, with promising first results and availability of laser-accelerated protons, experiments should be repeated with laser-accelerated protons and extended to several tumour entities to define its RBE on a broader level. Additionally, with the prospect of implementation of this new treatment modality into the clinic, investigations of the effects on normal tissue (e.g. skin) are mandatory.
Additionally, to prepare the clinical use of carbon ions, where radiobiological data are generally sparse, experiments are also in progress at SNAKE to explore the radiobiological properties and advantages of carbon ions versus protons, like less dependency of cell cycle distribution or tissue oxygenation.