Radio-enhancement by gold nanoparticles and their impact on water radiolysis for x-ray, proton and carbon-ion beams.

ABSTRACT

Gold nanoparticle (GNP) radio-enhancement is a promising technique to increase the dose deposition in a tumor while sparing neighboring healthy tissue. Previous experimental studies showed effects on cell survival and tumor control for keV x-rays but surprisingly also for MV-photons, proton and carbon-ion beams. In a systematic study, we use the Monte Carlo simulation tool TOPAS-nBio to model the GNP radio-enhancement within a cell as a function of GNP concentration, size and clustering for a wide range of energies for photons, protons and, for the first time, carbon-ions. Moreover, we include water radiolysis, which has been recognized as a major pathway of GNP mediated radio-enhancement. At a GNP concentration of 0.5% and a GNP diameter of 10 nm, the dose enhancement ratio was highest for 50 keV x-rays (1.36) and decreased in the orthovoltage (1.04 at 250 keV) and megavoltage range (1.01 at 1 MeV). The dose enhancement linearly increased with GNP concentration and decreased with GNP size and degree of clustering for all radiation modalities. While the highest physical dose enhancement at 5% concentrations was only 1.003 for 10 MeV protons and 1.004 for 100 MeV carbon-ions, we find the number of hydroxyl ([Formula see text]) altered by 23% and 3% after 1 [Formula see text]s at low, clinically-relevant concentrations. For the same concentration and proton-impact, the G-value is most sensitive to the nanoparticle size with 46 times more radical interactions at GNPs for 2 nm than for 50 nm GNP diameter within 1 [Formula see text]s. Nanoparticle clustering was found to decrease the number of interactions at GNPs, e.g. for a cluster of 25 GNPs by a factor of 3.4. The changes in G-value correlate to the average distance between the chemical species and the GNPs. While the radiochemistry of GNP-loaded water has yet to be fully understood, this work offers a first relative quantification of radiolysis products for a broad parameter-set.