Monte Carlo Simulation of Microscopic Dose Enhancement of Glucose Conjugated Gold Nanoparticles for the I-125 Radioactive Seeds Brachytherapy

Abstract

To investigate the microscopic energy deposition effect of glucose conjugated gold nanoparticles (Glu-GNPs) within a tumor irradiated by I-125 radioactive seeds on the nanometer/cell scale, and to quantify the corresponding microscopic dose enhancement factor (mDEF) around Glu-GNPs based on the real intra-cellular localization and spatial distribution of Glu-GNPs. Materials/Methods: The spectra of secondary electrons from atoms of gold and molecules of water under I-125 seeds irradiation of colorectal CL-187 cells cultured with culture medium added with Glu-GNPs was simulated with the Monte Carlo code Geant4. The simulation was based on the real Glu-GNPs intra-cellular localization and distribution observed with a transmission electron Microscope (TEM). The gold/water electron dose point kernels and corresponding mDEF was computed based on the simulated spectra of secondary electrons. Results: The fluence of secondary electron was increased by a factor up to 100 over radial distances of 10 um, when Glu-GNPs was added. For the tested Glu-GNPs size and concentration, the microscopic energy deposition increased by a factor up to 500 and 100 in the area immediately surrounding the Glu-GNPs and 5 um far from the Glu-GNPs. The mDEF around the Glu-GNPs ranged from 10 to 100 within 5-30 um far from Glu-GNPs, and decreased to less than 5% beyond a radial distance of 50 um. The formation of intracellular nanoparticle clusters increased the maximum mDEF by more than 100% within 10 um from the clusters. Conclusion: Glu-GNPs can significantly enhance the microscopic energy deposition for I-125 radioactive seeds brachytherapy of tumors. The significant microscopic dose enhancement effect is limited within 30 um from the Glu-GNPs. The active tumor targeting strategy using Glu-GNPs is beneficial to maximize the radiobiological benefit from brachytherapy using I-125 radioactive seeds, especially the formation of Glu-GNPs clusters within the tumor cells.

A detailed Monte Carlo evaluation of 192Ir dose enhancement for gold nanoparticles and comparison with experimentally measured dose enhancements

“…DEFs for low-energy sources were calculated to be higher than those for higher-energy sources. Monte Carlo has also been utilized by Yang et al to explore the microscopic dose enhancement of glucose-conjugated GNPs for I-125 (Yang et al 2016). They found that dose is enhanced by 10-100X in regions 5-30 µm from the GNP surface.…”