Photosensitizers play a key role in photodynamic therapy as a drug that is activated by light. In this thesis, the effect of ionizing radiation on the generation of singlet oxygen when using photosensitizers (Chlorin e6) and photocatalysts (titanium dioxide) was studied. By using radionuclides and photosensitizers (PS), cells can be killed with reactive oxygen species (ROS) which are produced by PS under influence of radiation that is emitted by radioactive decay. ROS are produced naturally in cells, but an excess of ROS can lead to damage to proteins, nucleic acids, lipids, membranes and organelles, which can lead to activation of cell death processes such as apoptosis. The focus of this thesis is the production of singlet oxygen which is a type of ROS. Indium-111, lutetium-177 and yttrium-90 which decay by different types of radiation have been used as radiation sources. In this research, the influence of these different radiation sources have been tested on Ce6 and TiO2 and their ability to produce singlet oxygen. Results show that Ce6 and TiO2 have increased production of singlet oxygen when exposed to ionizing radiation. Ce6 generates singlet oxygen when irradiated by both low energy gamma sources and high energy beta-minus radiation, while TiO2 generates singlet oxygen when irradiated by high energy beta-minus radiation.

Radiotherapy is a vital component in the treatment of malignancies, with approximately 50 to 70% of cancer patients receiving it at some point. This therapy consists of irradiating the affected body part with an external beam of ionising radiation. A limitation of this technique is its damaging effect on healthy cells surrounding the tumour. Semiconducting nanoparticles could offer a solution to this, as these compounds can generate reactive oxygen species (ROS). ROS are a group of free radicals that are known to be able to damage DNA and potentially cause necrotic or apoptotic cell death. Using these metal nanoparticles could increase the radiation damage to malignant cells during radiotherapy, without raising the risk of cell death for the surrounding tissue. Especially TiO2 nanoparticles have been increasingly studied due to their ability to produce singlet oxygen, one of the most reactive ROS, while also having low toxicity and cost. However, many aspects of the ROS-formation remain unclear, including certain ROS production pathways. This report will therefore focus on the ability of TiO2 to produce specific ROS in response to ionising radiation, which will primarily be compared to the ROS formation through the radiolysis of water. The focus lies on the detection of singlet oxygen and hydrogen peroxide (H2O2 ) after irradiation by either a Co-60 gamma or a low energy X-ray source over a range of 5 to 40 Gy. Their concentrations are detected by fluorescence spectroscopy for singlet oxygen, and by UV-VIS spectroscopy for hydrogen peroxide. The results were promising for the use of TiO2 in radiotherapy, with both MilliQ water and TiO2 being able to produce singlet oxygen in increasing amounts over the entire researched irradiation range for both radiation sources; Moreover, TiO2 could produce a significantly larger amount of this ROS than the MilliQ water samples did. The hydrogen peroxide detection experiments were first conducted with ZnO instead of TiO2 . During these, the trends observed for the H2O2 concentration were similar to the ones obtained during the singlet oxygen experiments. The main difference was that the ZnO samples produced approximately the same amount of H2O2 as the MilliQ water samples for X-ray irradiation, instead of higher values. Lastly, the hydrogen peroxide concentration in both TiO2 and ZnO samples was measured after irradiation by Co-60. ZnO exhibited an upward trend in which the H2O2 molarity increased as the applied dose got higher. The detected H2O2 levels in the TiO2 samples were, on the other hand, relatively stagnant. This observation is likely attributed to a relatively high extent of either the degradation, conversion, or adsorption of this ROS at the surface of TiO2

Cancer is often treated by radiation therapy. There are three types of radiation therapy: external beam therapy, brachytherapy and radionuclide therapy. A downside to radiation therapy is its damaging effect on healthy tissue. A different type of treatment is photodynamic therapy. In PDT photo-active substances are being used to generate reactive oxygen species under irradiation. These ROS are a group of radicals which can cause damage to the DNA and in some cases cause necrotic or apoptotic cell death. By combining radiotherapy and PDT, the effectiveness of the treatment can be enhanced. Among different ROS, singlet oxygen is the most effective in causing DNA damage. As the nanoparticle titaniumdioxide and the photo-active molecule chlorin e6 can generate ROS under ionizing radiation, it is very attractive to look further into how much singlet oxygen they can generate. This report will focus on the singlet oxygen generating abilities of the photo-active substances TiO2 and Ce6 under the irradiation of lutetium-177 and iodine-125. The relative amounts of generated singlet oxygen are measured using a probe called Singlet Oxygen Sensor Green and fluorescence spectroscopy. The experiments using 177Lu, did not show a lot of promise as a decrease in fluorescence intensity was seen in the radioactive samples. It is possible that 177Lu precipitates despite of its chelation with DTPA and the beta-minus particles might have destroyed the SOSG probe. When comparing the Ce6 samples with the TiO2 samples, the TiO2 samples show much higher intensities. A possible explanation for this result might be the fact that 177Lu destroys both the SOSG and Ce6, whereas TiO2 is not an organic molecules and it thus not destroyed by 177Lu. The intensities of the Ce6 samples was higher than the control group. This suggests there is some positive influence of Ce6 on the generation of singlet oxygen under irradiation of 177Lu. The experiments using 125I showed promise as the control samples and Ce6 samples showed an increased intensity in the presence of 125I. This suggest that under irradiation of 125I more singlet oxygen is generated than without. The TiO2 samples show inconclusive results and thus no trend can be seen between the exposed and non-exposed samples. This is possible due to some TiO2 particles being present in the eluate.