Microbeam Radiation Therapy Bio-Dosimetry Enhanced by Novel Radiosensitiser Combinations in the Treatment of Brain Cancer

<b>Background/Objectives</b>: Brain cancer is notoriously resistant to traditional treatments, including radiotherapy. Microbeam radiation therapy (MRT), arrays of ultra-fast synchrotron X-ray beams tens of micrometres wide (called peaks) and spaced hundreds of micrometres apart (valleys), is an effective alternative to conventional treatments. MRT's advantage is that normal tissues can be spared from harm whilst maintaining tumour control. Combining MRT with targeted radiosensitisers, such as nanoparticles, chemotherapeutic drugs, and halogenated pyrimidine drugs, can further improve radiotherapy by enhancing radiation damage. However, the underlying mechanisms of MRT are still being understood, which is essential to ensuring the reliable and successful use of MRT. <b>Methods</b>: An in vitro study was performed using γH2AX imaging, and quantification was performed via confocal microscopy and a clonogenic cell survival assay. <b>Results</b>: We show that methotrexate chemotherapeutics and iododeoxyuridine enhance MRT cell-killing and thulium oxide nanoparticles (TmNPs) broaden MRT peaks, and using γH2AX immunofluorescent confocal microscopy to quantify DNA damage, we further our knowledge of MRT mechanisms. γH2AX images verify the biological responses of cells aligning with the physical collimation of MRT, and we can accurately measure MRT microbeam characteristics bio-dosimetrically. The peak-to-valley dose ratio (PVDR), the ratio of the peak dose to the valley dose that characterises an MRT field, was accurately measured biologically using γH2AX imaging, despite studies previously finding this challenging. <b>Conclusions</b>: The measurement of biological PVDR has been performed for the first time with high-Z radiosensitisers, including nanoparticles, and several novel radiosensitiser-enhanced MRT mechanisms were discovered. Our results deepen our understanding of MRT with radiosensitisers, and can contribute to its accurate and future successful use in treating cancer.