Author: Ramin Abolfath, Alejandro Bertolet, Kofi M. Deh, Rao Khan, Vanessa Sanders, Daniel Suarez-Garcia đ¨âđŹ
Affiliation: Massachusetts General Hospital and Harvard Medical School, University of Sevilla, Brookhaven National Laboratory, Howard University đ
Purpose: To compare the efficacy of 225Ac to 90Y for local cancer therapy by quantifying DNA damage using Monte Carlo simulations.
Methods: The TOPAS n-Bio toolkit was used to simulate the irradiation of an isolated cell nucleus (TsNucleus model, radius = 4.65 Οm) by 90Y nanoparticles (radius = 60 nm, Eβ-,mean = 0.94 MeV, R β-,mean = 2.5 mm, activity = 0.031 GBq), where Eβ-,mean and R β-,mean are the mean energy and range of the beta spectrum. The concentration of nanoparticles around the nucleus was modeled with the density function, 0.607 * exp(-0.454 * r) + 0.382 where r is the distance from the center of the nucleus, based on data suggesting this distribution for 60 nm nanoparticles. The results were compared to irradiation by alpha particles from 225Ac (Eι+,mean = 5.84 MeV, R ι+,mean = 0.05 mm, activity = 24.8 kBq). Both simulations were scored for 10 histories. Chromosome repair was simulated using the MEDRAS toolkit. Radiobiological effectiveness () for the initial DNA damage was determined as the ratio of the slopes of linear fits to the absorbed dose versus DNA damage plots with intercepts set to zero.
Results: The average number of DSBs was 111 for 225Ac compared to only 0.04 for 90Y. While all 90Y DSBs were repaired correctly, 66 of the 225Ac DSBs were incorrectly repaired. was determined to be 20.3/4.27= 4.76, which is close to the value of 5 recommended for use in radiation therapy with alpha particles.
Conclusion: This study demonstrates the superior DNA damage potential of 225Ac over 90Y in local radiotherapy suggesting greater therapeutic efficacy of direct 225Ac therapy for liver tumors. Future research will refine RBE estimates with 90Y DNA misrepair, which was not observed in this study.