Purpose: Sub-cellular characterization of dose for therapeutic radiopharmaceutical agents is necessary due to the heterogeneous spatial uptake of these agents in the tumor microenvironment and the short range of their decay products, especially for alpha- and auger electron-emitting drugs. In this work we present initial physics benchmarking results of a GEANT4 microdosimetry platform for sub-cellular dosimetry applications capable of transforming confocal fluorescent microscopy Z-stack images into voxelized phantoms with corresponding radionuclide distribution and executing simulations based upon the imported geometry, source distribution, and radionuclide.
Methods: Three isotopes were investigated in this work: Â¹Â²â?µI, â?¹â?°Y, and Â²Â²Â³Ra. Cellular S-values of voxelized spheres are compared to MIRDCELL values for Â¹Â²â?µI and â?¹â?°Y. Energy spectra were computed for all isotopes and the number of auger emissions per Â¹Â²â?µI decay were computed and compared to literature. GEANT4-DNA physics libraries were utilized to ensure accurate modeling of sub-micron level dose deposition. To demonstrate the impact of realistic geometrical definitions, the dose distribution of a uniform source distribution is compared between a realistic human ovarian cancer cell and a sphere of an equivalent volume.
Results: Computed cellular S-values S(N->N) for Â¹Â²â?µI agree within 9% MIRDCELL and S(N->N) values for â?¹â?°Y agree within 22% of MIRDCELL values, likely attributable to differences in physics definitions for low energy auger emissions and methodological physics differences (e.g. MIRDCELLâ€™s condensed history vs. GEANT4-DNA single scatter). Computed energy spectrums for all isotopes and the auger emissions per decay computed for Â¹Â²â?µI agreed well with those found in literature. Simulations performed indicate spherical geometries overpredict dose to the cell.
Conclusion: Initial benchmarking of a microdosimetry platform for the analysis of targeted radionuclide therapy agents at the sub-cellular level has been conducted. Simulations performed highlight the importance of utilizing single-scatter physics models for accurately modeling auger and alpha emitters.