Abstract
Introduction: We develop a new method that drastically speeds up radiobiological Monte Carlo radiation-track-structure (MC-RTS) calculations on a cell-by-cell basis. Methods: The method is based on random sampling and superposition of single-particletrack (SPT) standard DNA damage (SDD) files from a “pre-calculated” data library, constructed using the RTS code TOPAS-nBio, with “time stamps” manually added to incorporate dose-rate effects. This time-stamped SDD file can then be input into MEDRAS, a mechanistic kinetic model that calculates various radiation-induced biological endpoints, including DNA double strand breaks (DSBs), misrepairs and chromosomal aberrations, and cell death. As a benchmark validation of the approach, we calculate the predicted energy-dependent DSB yield and the ratio of direct-to-total DNA damage, both of which agree with published in-vitro experimental data. We subsequently apply the method to perform superfast cell-by-cell simulation of an experimental in-vitro system consisting of neuroendocrine tumor cells uniformly incubated with 177Lu. Results and discussion: The results for residual DSBs, both at 24 and 48 h post-irradiation, agree well with the published literature values. Our work serves as a proof-of-concept demonstration of the feasibility of cost-effective “in silico clonogenic cell survival assay” for the computational design and development of radiopharmaceuticals, and novel radiotherapy treatments more generally.
Original language | English |
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Article number | 1284558 |
Journal | Frontiers in Nuclear Medicine |
Volume | 3 |
DOIs | |
State | Published - 2023 |
Funding
This work was partly supported by the Office of Biological and Environmental Research’s (BER), Biological Systems Science Division (BSSD), and Laboratory Directed Research and Development Program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the U. S. Department of Energy. Parts of this work have been authored by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. Acknowledgments
Keywords
- DNA double strand breaks
- Monte Carlo
- cell-by-cell radiobiological modeling
- radiation track structure
- standard DNA damage data