Investigation of singlet oxygen generation by photo-active substances when excited by ionizing radiation

Abstract

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.