Here we will perform preclinical investigations on tumour spheroids and mouse tumours structured in four major sub-projects. In the first one we compare the effects of carbon ions versus protons on tumour spheroids which will be irradiated in the absence and presence of radiosensitisers (e.g. heat shock protein 90 inhibitors) at the ion microprobe SNAKE. To characterise radiation damage, cytotoxic and genotoxic effects are measured and compared.
These experiments will be extended to pre-clinical studies in mouse tumours at CALA as soon as suitable beams from LION with energies above 25 MeV for protons and above 40 MeV / u for carbon ions become available. In the second sub-project the specific effects of protons and carbon ions on the membrane lipidomics and proteomics of tumour cells will be studied. The mechanisms of cell death induced by selective damage of the plasma membranes will be characterised using specific antibodies, unique lipid specific reagents such as toxins and Raman spectroscopy using cell monolayers and a three-dimensional tumour spheroid model at SNAKE.
Third, microbeam irradiations with highly focused protons and intermittent gaps will be studied, which are expected to result in reduced damage of normal tissues while maintaining tumour control. This work will be performed at SNAKE, since it is the only facility where it is possible to bunch protons in space with 0.2 ym beam diameter. The experiments will be performed in established tumour mouse models.
Finally, we will implement tumour irradiations using laser-driven protons, carbon ions and brilliant X-ray beams as soon as such beams are available at CALA using the proton / ion source LION and the X-ray sources BRIX and SPECTRE. We will compare biological effects of the ultra-high dose rate of laser-driven proton acceleration at CALA with conventional proton acceleration at SNAKE.