Physical dose enhancement of gold nanoparticles and their impact on water radiolysis in radiotherapy

Gold nanoparticle (GNP) radio-sensitization is a promising technique to increase the dose deposition in the tumor while sparing neighboring healthy tissue. The sensitization is most pronounced for keV x-rays, where the mass energy-absorption coefficient of gold is up to 150 times larger than that of soft tissue. Measurements in vitro and in vivo also showed an effect on cell survival and tumor control for other modalities such as MV photons and proton beams, where the physical dose enhancement by GNPs is expected to be negligible.
Most simulation studies have, thus, focused on photon irradiation of isolated GNPs in water neglecting experimental evidence of GNP clustering within cells. In a systematic study, we use the Monte Carlo simulation tool TOPAS-nBio to model the GNP radio-sensitization within a cell as a function of GNP concentration, size and clustering for a wide range of energies for photons, protons and carbon ions. Moreover, we include water radiolysis and subsequent chemistry as implemented in Geant4-DNA.
While the physical dose enhancement for 10MeV protons at 1% GNP concentration was only 0.07% compared to 62% for 50keV photons, we find the yield of reactive oxygen species change by up to 15% which could partly explain the experimental dose enhancement for protons.