Monte Carlo-based dosimetry and optimization of a custom alpha cell irradiation setup

Objective. When combined with targeting agents, alpha-particle-emitting radionuclides show promise in treating hypoxic tumors and micrometastases. These radionuclides exhibit a high relative biological effectiveness (RBE), attributed to their high linear energy transfer, and induce complex DNA damage within targeted cells. However, most clinical experience and radiobiological data are derived from photon irradiation. To optimize alpha-particle-based treatments, further research is needed to refine their RBE estimates. This study aimed to characterize and optimize a custom in-vitro cell irradiation setup for alpha-particle RBE studies using 241Am through Monte Carlo simulations. Approach. A Geant4-based Monte Carlo simulation model was used to simulate a custom cell well setup. An 241Am (48 kBq) source was positioned beneath the well with an adjustable source-to-surface distance (SSD). The spectra of decay products was calculated with 6.5 x109 simulated 241Am decay events. Simulations were conducted for SSD values of 2 mm, 5 mm, and 7 mm under three scenarios: (A) total dose rate from all decay products, (B) excluding gamma-emissions, and (C) excluding secondary particles. Results were compared to published spectra and a published dose rate (0.1 Gy min-1) as validation. Main results. The validation dose rate was 0.1136 Gy min-1. Photons of 13.9-59.5 keV and alpha-particles of 5.39-5.48 MeV were observed. The dose inhomogeneity across the cells was around 30%, 10%, and 5% in the 2, 5, and 7 mm SSD setups, respectively. The corresponding total dose rates in cells for the three SSDs were 0.583, 0.146, and 0.0830 Gy min-1. The dose rate contributions were 90% from alpha-particles, less than 0.07% from gamma-emissions, and 9%-10% from secondary particles. Significance. To accurately assess radiobiological effects, it is important to consider the full decay spectrum of radionuclides and their secondary particles in dosimetry calculations. These findings will aid in refining experimental setups for future in-vitro studies, contributing to more reliable RBE calculations.