Author: Zakaria Aboulbanine, Greeshma A. Agasthya, Paul Inman, Anuj J. Kapadia, Anthony Hong Cheol Lim, Jayasai Ram Rajagopal ðĻâðŽ
Affiliation: Oak Ridge National Laboratory, Georgia Institute of Technology ð
Purpose: The fundamental concept of radiopharmaceutical therapy involves binding radioisotopes to molecules with a known biokinetic distribution, which ensures that the targeted organs receive higher radioisotope concentrations with minimum exposure to other areas. The DNA damage pattern in the exposed organs will depend on several factors. In this work, we simulated the yield of chemical species and quantified the distribution of DNA damage for three radiosotopes widely used for radiopharmaceutical therapy.
Methods: Using the TOPAS-nBio code, condensed history and track structure Monte Carlo simulations were combined with radiation chemistry to model the interaction of radioisotopes with water. Two simulation models were used with a point-like source at the origin: 1) a 5 Ξm water sphere to estimate chemical yield, and 2) a cell nucleus model of 4.65 Ξm radius placed within a 14 Ξm water box to simulate DNA damage, the associated products, and energy spectra were analyzed for each of the three sources considered: Lu-177, Y-90 and I-131. The simulated processes include the following modules: radioactive decay; electromagnetic interaction for DNA physics, and radiation chemistry. Normalized time dependent chemical yield (G-value) distribution of different radicals were calculated for OH, hydrated electrons, and H2. The direct and indirect DNA damage was assessed by calculating the normalized Single Strand Breaks (SSB) and Double Strand Break (DSB) distributions.
Results: The chemical yield of highly reactive radicals, and DNA damage depend on the decay products of a radionuclide. At 1 Ξs, Y-99 showed the highest OH radical yield, with 2.7 molecules/100 eV. Regarding DNA damage, Lu-177 exhibited the greatest score, with 7.6 DSB/Gy/Gbp.
Conclusion: The highest DNA damage is caused by the lowest average kinetic energy deposit spectrum obtained for Lu-177 in this case. Small variations of energy deposit in the keV range have a noticeable impact on the final DNA damage outcome.