AUTHOR=Lim A. , Andriotty M. , Yusufaly T. , Agasthya G. , Lee B. , Wang C. TITLE=A fast Monte Carlo cell-by-cell simulation for radiobiological effects in targeted radionuclide therapy using pre-calculated single-particle track standard DNA damage data JOURNAL=Frontiers in Nuclear Medicine VOLUME=3 YEAR=2023 URL=https://www.frontiersin.org/journals/nuclear-medicine/articles/10.3389/fnume.2023.1284558 DOI=10.3389/fnume.2023.1284558 ISSN=2673-8880 ABSTRACT=Introduction

We developed a new method that drastically speeds up radiobiological Monte Carlo radiation-track-structure (MC-RTS) calculations on a cell-by-cell basis.

Methods

The technique is based on random sampling and superposition of single-particle track (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, such as DNA double-strand breaks (DSBs), misrepairs and chromosomal aberrations, and cell death. As a benchmark validation of the approach, we calculated the predicted energy-dependent DSB yield and the ratio of direct-to-total DNA damage, both of which agreed with published in vitro experimental data. We subsequently applied the method to perform a 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, are in line with the published literature values. Our work serves as a proof-of-concept demonstration of the feasibility of a cost-effective “in silico clonogenic cell survival assay” for the computational design and development of radiopharmaceuticals and novel radiotherapy treatments more generally.