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Project C.3.3

Cellular and molecular radiation biology of laser-driven particle therapy

Here we focus on the reasons for enhanced relative biological efficiency (RBE) of high linear energy transfer (LET) irradiation compared to low LET irradiation and on the  biological factors affecting the RBE. While advantages of high LET irradiation in the treatment of radioresistant tumour cells are often claimed, actual data are scarce. Systematic analysis will help to elucidate the relative relevance of LET in modern  radiotherapy. For this purpose we make use of the Munich Tandem Accelerator to irradiate cells with protons (low LET), carbon ions (high LET) and ions with intermediate LET. Unique in the world is the possibility to use the microprobe SNAKE in order to bunch  protons in time (< 1 ns) and space (~ 0.2 ym beam diameter). With this setup it can be tested whether the enhanced RBE of heavier ions is solely due to spatial clustering of ionisations, as is generally assumed.

By varying the pulse in size (from 0.2 ym to 10 ym) and duration (from nanoseconds to seconds), it will be tested how the enhanced RBE is created from the ionisation density and simultaneousness of induction. These studies will be complemented by ultrafast radiation biology studies on radical behaviours under the different conditions and sub-cellular mapping of electron densities and chemical modifications using soft-X-ray sub-cellular microscopy.

The influence of genetic alterations on the relative sensitivities to differing LET will be investigated by irradiating cell lines with defined genetic deficiencies. We aim at establishing three-dimensional tissue models from these cells by cultivation with matrix-forming materials. In addition, the influence of cell cycle state and proliferation velocity will be investigated. Once CALA is operational, experiments will be conducted with laser-driven beams. There it is expected that higher ion energies become available as well as a sub-ns pulse delivery for investigating dose rate and ionisation density effects.