Thesis defense of Carina Behrends

In radiotherapy, it is fundamental to manage the radiation damage with respect to tumor control and normal tissue complications. Thus, therapeutic strategies aim to find a compromise between the applicable dose for clonogenic cell death of the tumor cells and possible side effects. Radiobiological experiments may provide further insight into the damaging effects of radiation. Here, three different and independent research approaches in proton therapy physics from the millimeter to nanometer scale are introduced to improve radiobiological experiments and thus long-term therapeutic outcome. The first project presents a method to optimize field shaping in the treatment modality of proton pencil beam scanning in combination with collimating apertures. The fundamental relationship between spot position and aperture edge with respect to the maximization of the dose gradient is investigated in detail analytically, experimentally and in simulations. It has been shown that positioning the outer spots beyond the aperture edge and further combined with fluence modulation can obtain a sharper dose gradient. Thus, a lateral dose fall-off from 80% to 20% of the relative dose profile can be achieved within a few millimeters. In a second project, an experimental setup is developed and optimized to deliver protons originally accelerated to clinical energies as efficiently as possible with an arbitrary energy down to only a few MeV. The analysis of energy spectra, which are affected by range scattering and fluence loss especially for low-energy protons, shows that there is an optimal material thickness for decelerating protons to a required energy. This allows the provision of proton fields of all energies relevant to radiobiology, especially down to a few MeV with high linear energy transfer and ranges on the scale of 100 μm, for performing radiobiological experiments. The third project investigates the radiosensitizing effect of platinum nanoparticles (PtNPs) in proton therapy, which can potentially induce increased tumor control during treatment. Promising results have been reported in the use of metal nanoparticles in radiotherapy in terms of increased treatment efficacy. However, the underlying mechanism of the radiosensitizing effect of PtNPs in proton therapy remains unclear. Experiments on tissue-like samples with and without PtNPs have demonstrated no difference on a macroscopic scale in the stopping power or energy deposition of protons in the presence of PtNPs. Thus, the project provides experimental evidence that the radiosensitizing effect of PtNPs in proton therapy is not due to an enhanced energy deposition, thereby directing the research focus of this effect to the chemical and biological phase of the radiation effect. Accordingly, the projects investigated in this work provide individual contributions to the radiobiological research and thus to the improvement of the radiation effect in proton beam therapy.

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