title: A Monte Carlo-based model of gold nanoparticle radiosensitization accounting for increased radiobiological effectiveness.
abstract: Radiosensitization using gold nanoparticles (AuNPs) has been shown to vary widely with cell line, irradiation energy, AuNP size, concentration and intracellular localization. We developed a Monte Carlo-based AuNP radiosensitization predictive model (ARP), which takes into account the detailed energy deposition at the nano-scale. This model was compared to experimental cell survival and macroscopic dose enhancement predictions. PC-3 prostate cancer cell survival was characterized after irradiation using a 300 kVp photon source with and without AuNPs present in the cell culture media. Detailed Monte Carlo simulations were conducted, producing individual tracks of photoelectric products escaping AuNPs and energy deposition was scored in nano-scale voxels in a model cell nucleus. Cell survival in our predictive model was calculated by integrating the radiation induced lethal event density over the nucleus volume. Experimental AuNP radiosensitization was observed with a sensitizer enhancement ratio (SER) of 1.21 ± 0.13. SERs estimated using the ARP model and the macroscopic enhancement model were 1.20 ± 0.12 and 1.07 ± 0.10 respectively. In the hypothetical case of AuNPs localized within the nucleus, the ARP model predicted a SER of 1.29 ± 0.13, demonstrating the influence of AuNP intracellular localization on radiosensitization.
authors.affiliation: Department of Medical Biophysics, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Lechtman
authors.forename: S
authors.initials: S
authors.lastname: Mashouf
authors.forename: N
authors.initials: N
authors.lastname: Chattopadhyay
authors.forename: B M
authors.initials: BM
authors.lastname: Keller
authors.forename: P
authors.initials: P
authors.lastname: Lai
authors.forename: Z
authors.initials: Z
authors.lastname: Cai
authors.forename: R M
authors.initials: RM
authors.lastname: Reilly
authors.forename: J-P
authors.initials: JP
authors.lastname: Pignol
mesh_terms: D000042:Absorption; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006046:Gold / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D053768:Metal Nanoparticles; D009010:Monte Carlo Method; D011836:Radiation Tolerance / Q000187:drug effects*; D011853:Radiobiology
chemical_list: D006046:Gold