Reproducibility study of Monte Carlo simulations for nanoparticle dose enhancement and biological modeling of cell survival curves

Abstract

Nanoparticle-derived radiosensitization has been investigated by several groups using Monte Carlo simulations and biological modeling. In this work we replicated the physical simulation and biological modeling of previously published research for 50 nm gold nanoparticles irradiated with monoenergetic photons, various 250 kVp photon spectra, and spread-out Bragg peak (SOBP) protons. Monte Carlo simulations were performed using TOPAS and used condensed history Penelope low energy physics models for macroscopic dose deposition and interaction with the nanoparticle; simulation of the microscopic dose deposition from nanoparticle secondaries was performed using Geant4-DNA track structure physics. Biological modeling of survival fractions was performed using a local effect model-type approach for MDA-MB-231 breast cancer cells. Physical simulation results agreed extraordinarily well at all distances (1 nm to 10 µm from nanoparticle) for monoenergetic photons and SOBP protons in terms of dose per interaction, secondary electron dose enhancement factor, and secondary electron spectra. For 250 kVp photons the influence of the gold K-edge was investigated and found to appreciably affect the results. Calculated survival fractions similarly agreed well within one order of magnitude at macroscopic doses (i.e. without nanoparticle contribution) from 1 Gy to 10 Gy. Several 250 kVp spectra were tested to find one yielding closest agreement with previous results. This highlights the importance of a detailed description of the low energy (< 150 keV) component of photon spectra used for in-silico, as well as in-vitro, and in-vivo studies to ensure reproducibility of the experiments by the scientific community. Both, Monte Carlo simulations of physical interactions of the nanoparticle with photons and protons, as well as the biological modelling of cell survival curves agreed extraordinarily well with previously published data. Further investigation of the stochastic nature of nanoparticle radiosenstiziation is ongoing.

Comment on “Reproducibility study of Monte Carlo simulations for nanoparticle dose enhancement and biological modeling of cell survival curves” by Velten et al [Biomed Phys Eng Express 2023;9:045004]

“…Assume a surface dose of D 1 = 100 Gy and that 1000 GNPs undergo an ionizing interaction. (This corresponds approximately to the case of 80 keV photons at a dose without GNPs of D 0 = 1, cf Table 1 in [1]). Then, D b,3…”

“…m If the sphere and the circle both have a diameter of 8 μm, as considered by Velten et al [1], then h n is about 5.3 μm.…”

“…In their recent article, Velten et al [1] replicated the physical simulation and biological modeling of previously published research [2] on 50 nm gold nanoparticles (GNPs) irradiated with different photon spectra or with protons in a spread-out Bragg peak (SOBP). For the biological modeling, they used a variant of the local effect model (LEM), which they called the "LEM approach in 2D" and which is based on the assumption of an infinitesimally thin cell.…”

“…If this interpretation of the procedure is correct and if the dose kernels shown in Supplementary figure 5 of Velten et al [1] were used, this leads to an overestimation of the number of lesions and an underestimation of cell survival. This is because using a cross-section of the 3D dose profile is equivalent to assuming that the cell has the shape of a cylinder in which the dose profile is constant along the direction of the cylinder axis.…”

“…The gold-to-water ratio of the mass energy-absorption coefficients for the monoenergetic photon energies ranges from 11 (250 keV) to 145 (50 keV). If the weights of the differrent photon energies in the mock 250 kVp spectra are used (given in Table S1 of [1]), this ratio is between 58 and 87. Therefore, the macroscopic average dose under secondary particle equilibrium for the case of the GNPs uniformly distributed over the cells is expected to be higher.…”