Advances in Computational Radiation Biophysics for Cancer Therapy: Simulating Nano-Scale Damage by Low-Energy Electrons

Abstract

Computational radiation biophysics is a rapidly growing area that is contributing, alongside new hardware technologies, to ongoing developments in cancer imaging and therapy. Recent advances in theoretical and computational modeling have enabled the simulation of discrete, event-by-event interactions of very low energy ( 100 eV) electrons with water in its liquid thermodynamic phase. This represents a significant advance in our ability to investigate the initial stages of radiation induced biological damage at the molecular level. Such studies are important for the development of novel cancer treatment strategies, an example of which is given by microbeam radiation therapy (MRT). Here, new results are shown demonstrating that when excitations and ionizations are resolved down to nano-scales, their distribution extends well outside the primary microbeam path, into regions that are not directly irradiated. This suggests that radiation dose alone is insufficient to fully quantify biological damage. These results also suggest that the radiation cross-fire may be an important clue to understanding the different observed responses of healthy cells and tumor cells to MRT.

Dose enhancement effects to the nucleus and mitochondria from gold nanoparticles in the cytosol

“…Interestingly, this simulation study, as well as others (e.g. Kuncic (2015)) showed the importance of dose delocalisation due to Compton scatter and photoelectron ejection (i.e. secondary electrons moving from one part of the cell to another).…”

Nanoparticle radio-enhancement: principles, progress and application to cancer treatment

“…Most of these models are based on Monte Carlo simulations. Monte Carlo (MC) particle simulations can be used to model the physical and physico-chemical processes of radiation interactions with biological targets, but cannot be used to study radio-enhancement effects because the biological outcomes cannot be directly simulated (Kuncic 2015). However, MC-based models have developed which integrate MC simulations with mathematical radiobiological modeling (e.g.…”

Stochastic simulation of radium-223 dichloride therapy at the sub-cellular level

“…The Geant4 low energy electromagnetic physics model processes used to simulate ionizations have an energy cut-off of 250 eV . While it is possible to simulate ionization processes down to even lower energies, this is computationally expensive and beyond the scope of this paper (but see Kuncic (2014) and Byrne et al (2013)). Thus, indirect DNA damage could play an even more significant role in particle therapy than is currently thought.…”