Synchrotron facilities produce ultra-high dose rate X-rays that can be used for selective cancer treatment when combined with micron-sized beams. Synchrotron microbeam radiation therapy (MRT) has been shown to inhibit cancer growth in small animals, whilst preserving healthy tissue function. However, the underlying mechanisms that produce successful MRT outcomes are not well understood, either in vitro or in vivo. this study provides new insights into the relationships between dosimetry, radiation transport simulations, in vitro cell response, and pre-clinical brain cancer survival using intracerebral gliosarcoma (9LGS) bearing rats. As part of this groundbreaking research, a new image-guided MRT technique was implemented for accurate tumor targeting combined with a pioneering assessment of tumor dose-coverage; an essential parameter for clinical radiotherapy. Based on the results of our study, we can now (for the first time) present clear and reproducible relationships between the in vitro cell response, tumor dose-volume coverage and survival post MRT irradiation of an aggressive and radioresistant brain cancer in a rodent model. our innovative and interdisciplinary approach is illustrated by the results of the first long-term MRT pre-clinical trial in Australia. Implementing personalized synchrotron MRT for brain cancer treatment will advance this international research effort towards clinical trials.

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Nanoparticles, with their distinct properties that vary from their bulk material equivalent, continue to gain popularity for studies into multi-modal applications in medicine. This research introduces the use of thulium oxide nanoparticles for biological applications and characterizes the potential of this novel nanoparticle for image-guided radiotherapy of brain cancer. In this study, we investigate the structural characteristics of this nanoparticle, and reveal a significant dose enhancement towards radioresistant brain tumour cells in vitro that also underlies an improvement in the CT image contrast of brain tumours in vivo. The thulium oxide nanoparticles utilized in the investigations described in this article were measured to be 40-45 nm from x-ray diffraction and scanning electron microscopy data. In vitro investigations assessed the cell survival and DNA damage in 9 l gliosarcoma cells following irradiation with 150 kVp orthovoltage x-rays. Immediately after the 150 kVp irradiation (15 min) an increase in the number of γ-H2AX induced foci indicates the production of more double-strand DNA breaks. Following from the short time-frame irradiation outcomes, clonogenic cell survival assays confirmed long-term radio-sensitization, with the cell sensitivity increasing by a factor of 1.32 (measured at the 10% survival fraction) for the irradiated 9 l cells exposed to thulium nanoparticles. A simple CT experiment shows that our thulium nanoparticles suspended in water at concentrations >0.5 mg ml −1 (0.05-20 mg ml −1 investigated) are clearly observable against water. Extending the CT experiment to an in vivo investigation, cellular uptake of the nanoparticles was demonstrated through CT image enhancement of the cancer site in 9-to 10-week-old Fisher rats bearing 9 l gliosarcomas, 12 days after cell implantation. The 9 l cancer is clearly visible on the CT image after injecting 40 μg of nanoparticles (2 μl at 20 mg ml −1) directly to the cancer site (5.5 mm from the dura and 3.5 mm right laterally of the bregma, 5 mm depth). To our knowledge, this work demonstrates the first application of thulium nanoparticles in biology and medicine, for radiotherapy and image guidance purposes.