Synchrotron Modulated Activation Radiation Therapy: Developing a SMART approach for Brain Cancer Treatment

With high proliferation and inherent resistance to radiation and chemotherapy, brain cancers are among the most difficult cancers for early diagnosis and treatment. Synchrotron radiation consists of low divergence and high brilliance kilovoltage X-rays. This research explores the efficacy of synchrotron radiation for brain cancer radiosurgery and further demonstrates that high-Z nanoparticles can increase the cancer specificity of synchrotron radiation. This Synchrotron Modulated Activation Radiation Therapy (SMART) approach includes broad and microbeams radiation therapy (MRT) in combination with nanoparticles. The efficacy of SMART was explored in silico with Monte Carlo modelling, in vitro and in vivo studies.

Major findings of Monte Carlo modelling with Geant4 include the optimisation of nanoparticle dose enhancement in MRT, synchrotron broad beam and conventional radiotherapy, and the novel application of the Local Effect Model to predict cell survival with gold nanoparticles using newly developed track structure-based code. For the first time, novel metal oxide nanoparticles were shown to increase the effective radiation dose to 9L glioblastoma cells in vitro with synchrotron radiation. Cell studies also led to the development of both a live cell nanoparticle detection method using confocal laser light scattering and the first in vitro cell survival prediction model for MRT. After optimising 9L cancer treatment in vitro, the first long term preclinical survival study was performed at the Australian Synchrotron with MRT of intracranial 9L tumours in Fischer rats. The first preclinical evidence of SMART was also obtained using novel thulium-based nanoparticles, which were also shown to enhance tumour contrast in CT imaging, making it a strong candidate for further SMART development. The preclinical study further pioneered methods for individualized MRT including treatment planning for brain cancer treatment, image-guided animal positioning and symptom management following MRT.

This current work provides the basis for further work that may eventually have application in targeting of difficult-to-treat tumours such as glioblastoma multiforme. These findings have produced 5 first author publications (with 3 more in preparation), and contributed towards 12 publications in total. This work has been presented at 21 conferences and workshops (international and domestic), and has been recognised with postgraduate excellence prizes from the Australian Institute of Physics (NSW branch) and the Australasian College of Physical Scientists & Engineers in Medicine at MedPhys17 and MedPhys20.