A method for converting dose-to-medium to dose-to-tissue in Monte Carlo studies of gold nanoparticle-enhanced radiotherapy

Abstract

Gold nanoparticles (GNPs) have shown potential in recent years as a means of therapeutic dose enhancement in radiation therapy. However, a major challenge in moving towards clinical implementation is the exact characterisation of the dose enhancement they provide. Monte Carlo studies attempt to explore this property, but they often face computational limitations when examining macroscopic scenarios. In this study, a method of converting dose from macroscopic simulations, where the medium is defined as a mixture containing both gold and tissue components, to a mean dose-to-tissue on a microscopic scale was established. Monte Carlo simulations were run for both explicitly-modeled GNPs in tissue and a homogeneous mixture of tissue and gold. A dose ratio was obtained for the conversion of dose scored in a mixture medium to dose-to-tissue in each case. Dose ratios varied from 0.69 to 1.04 for photon sources and 0.97 to 1.03 for electron sources. The dose ratio is highly dependent on the source energy as well as GNP diameter and concentration, though this effect is less pronounced for electron sources. By appropriately weighting the monoenergetic dose ratios obtained, the dose ratio for any arbitrary spectrum can be determined. This allows complex scenarios to be modeled accurately without explicitly simulating each individual GNP.

Heterogeneous multiscale Monte Carlo simulations for gold nanoparticle radiosensitization

“…Table presents dose ratios (dose‐to‐tissue relative to dose to a homogeneous tissue‐gold mixture) for various gold concentrations and source energies. While many values computed in the current work agree with the published values of Koger and Kirkby within the 1 σ statistical uncertainties indicated, all values agree within 2 σ uncertainties except for the 20 keV beam with 20 nm diameter GNPs at a concentration of 20 mg/g, which is at 2.1 σ . The largest percent difference observed is 2.6% for the 50 keV beam with 20 nm diameter GNPs having a concentration of 20 mg/g (quadrature sum of the 1 σ statistical uncertainties is 1.3%).…”

“…Photons and electrons were simulated down to 100 eV, and electrons leaving the microcavity were transported back into it for full energy deposition. Ratios of the dose‐to‐tissue relative to dose to the homogeneous blend of tissue and gold were published (to allow conversion of dose scored in a mixture to dose‐to‐tissue) for a range of source energies and GNP concentrations …”

“…We perform a verification of our MC simulations involving GNPs using the recent (independent) results of Koger and Kirkby. 13 Using PENELOPE, these researchers modeled monoenergetic photons or electrons incident on microcavities filled with either randomly distributed GNPs embedded in ICRU tissue 26 or a homogeneous mixture of gold and tissue. Photons and electrons were simulated down to 100 eV, and electrons leaving the microcavity were transported back into it for full energy deposition.…”

“…Research to connect the macroscopic and microscopic approaches has been limited and varying. To avoid modeling GNPs individually in a macroscopic volume yet still extract the DEF in pure tissue, Koger and Kirkby recently presented a database of factors to convert dose scored in a homogeneous blend of tissue and gold to dose scored in tissue containing discretely modeled GNPs . Some researchers have discretely modeled GNPs in a macroscopic volume using the simple geometry of a cubic lattice of GNPs embedded in an otherwise homogeneous water or tissue phantom .…”

“…To avoid modeling GNPs individually in a macroscopic volume yet still extract the DEF in pure tissue, Koger and Kirkby recently presented a database of factors to convert dose scored in a homogeneous blend of tissue and gold to dose scored in tissue containing discretely modeled GNPs. 13 Some researchers have discretely modeled GNPs in a macroscopic volume using the simple geometry of a cubic lattice of GNPs embedded in an otherwise homogeneous water or tissue phantom. [14][15][16][17][18] Cai et al 19 used a lattice on a cellular scale, creating a multi-cell configuration containing discretely modeled GNPs spanning (0.24 cm) 3 .…”