title: Nanodosimetric effects of gold nanoparticles in megavoltage radiation therapy.
abstract: OBJECTIVE
  The addition of gold nanoparticles (GNPs) to tumours leads to an increase in dose due to their high density and energy absorption coefficient, making it a potential radiosensitiser. However, experiments have observed radiosensitisations significantly larger than the increase in dose alone, including at megavoltage energies where gold's relative energy absorption is lowest. This work investigates whether GNPs create dose inhomogeneities on a sub-cellular scale which combine with non-linear dose dependence of cell survival to be the source of radiosensitisation at megavoltage energies.
  
  
  METHODS
  Monte Carlo simulations were carried out to calculate dose in the vicinity of a single GNP on the nanoscale. The effect of this nanoscale dose distribution was then modelled for MDA-MB-231 cells exposed to 2 nm GNPs, and compared to experimental results.
  
  
  RESULTS
  Dramatic dose inhomogeneities occur around GNPs exposed to megavoltage radiation. When analysed using the Local Effect Model, these inhomogeneities lead to significant radiosensitisation, in agreement with experimental results.
  
  
  CONCLUSIONS
  This work suggests that GNP radiosensitisation is driven by inhomogeneities in dose on the nanoscale, rather than changes in dose over the entire cell, which may contribute to the similar radiosensitisation observed in megavoltage and kilovoltage experiments. The short range of these inhomogeneities and the variation in enhancement in different cells suggests sub-cellular localisation is important in determining GNP radiosensitisation.
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland, UK. stephen.mcmahon@qub.ac.uk
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: McMahon
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Hyland
authors.forename: Mark F
authors.initials: MF
authors.lastname: Muir
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Coulter
authors.forename: Suneil
authors.initials: S
authors.lastname: Jain
authors.forename: Karl T
authors.initials: KT
authors.lastname: Butterworth
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Schettino
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Dickson
authors.forename: Alan R
authors.initials: AR
authors.lastname: Hounsell
authors.forename: Joe M
authors.initials: JM
authors.lastname: O'Sullivan
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Prise
authors.forename: David G
authors.initials: DG
authors.lastname: Hirst
authors.forename: Fred J
authors.initials: FJ
authors.lastname: Currell
mesh_terms: D001943:Breast Neoplasms / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006046:Gold / Q000494:pharmacology*; D006801:Humans; D053768:Metal Nanoparticles; D009010:Monte Carlo Method; D010315:Particle Accelerators; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011874:Radiometry / Q000379:methods*; D012044:Regression Analysis
chemical_list: D011838:Radiation-Sensitizing Agents; D006046:Gold