Author: Hamid Abdollahi Nasehabad, Mehrangiz Amiri, Mohammad Reza Deevband, Faraz Kalantari, Milad Peer-Firozjaei, Ali Shabestani Monfared, Ehsan Tajikmansoury 👨🔬
Affiliation: Biomedical Engineering and Medical Physics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Department of Radiology, University of British Columbia, Department of Radiation Oncology, University of Arkansas for Medical Sciences (UAMS), Department of Radiobiology and Medical Physics, Babol University of Medical Sciences, 1. Department of Radiobiology and Medical Physics, Babol University of Medical Sciences, Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine 🌍
Purpose:
Targeted radionuclide therapy (TRNT) with 213Bi- labeled radiopharmaceuticals is a promising approach in targeted alpha and beta therapy for cancer. This study aims to assess double-strand breaks (DSBs) by quantifying γH2AX, a marker of early DNA damage, in the MCF7 cell line. The evaluation combines Monte Carlo simulations with comparisons to experimental data.
Methods:
Geant4-DNA (version 11.3) Monte Carlo (MC) toolkit used to accurate modeling of MCF7 cells were geometrically consider as ellipsoids with semi-axes of 7.01 ± 0.33 μm, 2.50 ± 0.25 μm, and 5.30 ± 0.26 μm. A fractal-based DNA chain structure was simulated using a continuous Hilbert curve, achieving a base pair density of ~0.017 bp/nm³. Physical, physicochemical, and chemical processes in liquid water irradiation, including radiolytic effects was simulate in toolkit. Direct and indirect DNA damage, such as single and double-strand breaks, was calculated for energy deposition and free radical interactions resulting from the irradiation of 8 μCi of 213Bi in Geant4-DNA. Energy spectra were derived from MIRD data, and secondary particles were tracked using phase-space files. A DNA damage repair model based on Belov et al.'s framework was implemented in Python, incorporating four primary DSB repair pathways and simulating γH2AX formation through Michaelis-Menten kinetics.
Results:
Monte Carlo simulations quantified early DNA damage in MCF7 cells exposed to alpha and beta particles from 213Bi. The results aligned closely with experimental data on γH2AX yields over time (p-value < 0.05). Minimal error margins suggested potential contributions from cross-fire and bystander effects, warranting further exploration in radiopharmaceutical therapy.
Conclusion:
This study demonstrates the utility of Monte Carlo simulations in evaluating early DNA damage and repair mechanisms in radiopharmaceutical therapies. Evaluating the early radiobiological effects of new radiopharmaceuticals on different cancer cell lines, may enhance the design and optimization of cancer treatment strategies.