Author: Sang Hyun Cho, Sandun Y. Jayarathna, Amrit Kaphle 👨🔬
Affiliation: The University of Texas MD Anderson Cancer Center 🌍
Purpose: To assess the effectiveness of various nanoscale models of gold nanoparticle (GNP)-laden cells for Monte Carlo (MC) studies of GNP-mediated radiation dose enhancement/DNA damage.
Methods: Transmission electron microscopy (TEM) images of a Panc1 tumor cell containing GNPs were used to construct nanoscale cell models for Geant4 MC simulations. The 1-Slice TEM model utilized a single TEM image with realistic GNPs, while the Full 3D TEM model was reconstructed by stacking artificial slices generated through z-axis projections of the original TEM image. The Simple 3D model employed a basic elliptical cell representation with randomly distributed GNPs. All models incorporated a realistic fractal arrangement of chromatin fibers to simulate realistic DNA structure within the nucleus. Radiation-induced single-/double-strand breaks (SSBs and DSBs) were normalized to total dose and DNA base pair density (Gy⁻¹Gbp⁻¹), and the dose enhancement percentages were calculated to assess the effects of GNP distribution and model complexity on DNA damage estimation.
Results: For 250 kVp irradiation, the Simple 3D model showed the highest dose enhancement at 6.79%, followed by the Full 3D TEM model at 4.38%, and the 1-Slice TEM model at 2.72%. In contrast, for 6 MV irradiation, the Full 3D TEM model resulted in the highest enhancement at 14.95%, followed by the Simple 3D and 1-Slice TEM models at 10.57% and 5.25%, respectively. While the Simple 3D model overestimated both SSB and DSB enhancement for 250 kVp, it underestimated both enhancement for 6 MV. The Full 3D and 1-Slice TEM models showed similar SSB and DSB enhancement for 6 MV.
Conclusion: The Full 3D and 1-Slice TEM models, more realistically representing intracellular GNP distribution and cellular geometry, ensured more reliable estimation of GNP-mediated DNA damage enhancement under both irradiation scenarios. This investigation highlights the critical importance of GNP-laden cell models for MC studies of GNP-mediated radiosensitization.