Cellular lethal damage of 64Cu incorporated in mammalian genome evaluated with Monte Carlo methods

• DOI: 10.3389/fmed.2023.1253746
• Publication Date: 2023-09-29T09:23:01Z
• Authors: Jhonatan Carrasco...; José Ramos-Méndez; Elizabeth Padilla...; Miguel A. Avila-R...
• Keywords: Auger effect; Radionuclide therapy; Helix (gastropod)

Purpose Targeted Radionuclide Therapy (TRT) with Auger Emitters (AE) is a technique that allows targeting specific sites on tumor cells using radionuclides. The toxicity of AE critically dependent its proximity to the DNA. aim this study quantify DNA damage and radiotherapeutic potential promising radionuclide copper-64 ( 64 Cu) incorporated into mammalian Monte Carlo track-structure simulations. Methods A cell nucleus model diameter 9.3 μm available in TOPAS-nBio was used. cellular consisted double-helix geometrical 2.3 nm surrounded by hydration shell thickness 0.16 nm, organized 46 chromosomes giving total 6.08 giga base-pairs (DNA density 14.4 Mbp/μm 3 ). irradiated monoenergetic electrons radiation emissions from several radionuclides including 111 In, 125 I, 123 99m Tc addition Cu. For electrons, isotropic point sources randomly distributed within were modeled. chosen base pairs at two positions near central axis (1) 0.25 off (2) periphery (1.15 axis). all except for Tc, complete physical decay process explicitly simulated. only electron spectrum published data Double Strand Breaks (DSB) yield per direct indirect actions quantified. Results obtained compared measured calculated literature verification purposes. DSB yields Cu are first reported work. therapeutic effect (activity led 37% survival after divisions) determined terms number atoms would lead same DSBs 100 decays I. Simulations run until 2% statistical uncertainty (1 standard deviation) achieved. behavior as function energy consistent data, increased it reached maximum value 500 eV followed continuous decrement. Cu, when genome evaluated (2), 0.171 ± 0.003 0.190 DSB/decay, respectively. initial (per cell) cause estimated 3,107 28, corresponds an activity 47.1 0.4 × 10 −3 Bq. Conclusion Our results showed TRT has comparable effects currently used clinical practice.