Purpose: The recent surge in the interest and development of radiopharmaceutical therapy (RPT) agents requires the investigation of microdosimetry due to the short range of emissions and heterogeneous activity distributions. Monte Carlo microdosimetric simulations can accurately account for the heterogeneous activity distributions that can be present at the cellular level and will aid in the development of RPT treatment planning by accounting for the tumor microenvironment. This study created a model of an idealized tumor microenvironment using the Monte Carlo code, Geant4.
Methods: Geant4 simulations were compared cellular S-values of I-131, Lu-177, Y-90, and Br-77 to MIRD by modeling the tumor environment as an agglomeration of spherical cells. The tumor microenvironment was simulated as a cluster of liquid spherical 5 μm radius cells in both hexagonal and lattice configurations. Both source and target cellular S-values were calculated using Geant4 and validated using MIRDcell. Because the radionuclides investigated have different decay characteristics, physics lists, decay relative functions, and electron scattering cross-sections were analyzed using Geant4.
Results: The differences between Geant4 and MIRD were under 10% for I-131, Lu-177, and Y-90 and 15% for Br-77. The ARMflag function was required for accurately model Auger electron emissions. Appropriate physics lists were required for different radionuclides to account for the different emitting radiation energy ranges and interactions based on each decay scheme. Accordingly, Livermore physics was applied to Y-90, DNA_option8 was applied to I-131 and Lu-177, and DNA_option7 was applied to Br-77. Lastly, the electron scattering cross-sections, de-excitation, and fluorescence process were also considered.
Conclusion: A Geant4 microdosimetric tumor model was validated by a standard MIRD configuration. This tumor model is flexible and extendible to more realistic tumor cell and source activity configurations. Appropriate microenvironment modeling and radionuclide physics considerations can provide more optimal RPT treatment plans and account for more realistic dosimetric phenomenon.
Funding Support, Disclosures, and Conflict of Interest: BB is a co-founder of Voximetry, Inc., a nuclear medicine dosimetry company in Madison, WI.