title: Stochastic simulation of radium-223 dichloride therapy at the sub-cellular level.
abstract: Radium-223 dichloride ((223)Ra) is an alpha particle emitter and a natural bone-seeking radionuclide that is currently used for treating osteoblastic bone metastases associated with prostate cancer. The stochastic nature of alpha emission, hits and energy deposition poses some challenges for estimating radiation damage. In this paper we investigate the distribution of hits to cells by multiple alpha particles corresponding to a typical clinically delivered dose using a Monte Carlo model to simulate the stochastic effects. The number of hits and dose deposition were recorded in the cytoplasm and nucleus of each cell. Alpha particle tracks were also visualized. We found that the stochastic variation in dose deposited in cell nuclei ([Formula: see text]40%) can be attributed in part to the variation in LET with pathlength. We also found that [Formula: see text]18% of cell nuclei receive less than one sigma below the average dose per cell ([Formula: see text]15.4 Gy). One possible implication of this is that the efficacy of cell kill in alpha particle therapy need not rely solely on ionization clustering on DNA but possibly also on indirect DNA damage through the production of free radicals and ensuing intracellular signaling.
authors.affiliation: Brain and Mind Research Institute, Medical Imaging and Radiation Sciences Faculty Research Group, University of Sydney, Sydney, NSW 2006, Australia. School of Physics, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Y
authors.initials: Y
authors.lastname: Gholami
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: R
authors.initials: R
authors.lastname: Fulton
authors.forename: S
authors.initials: S
authors.lastname: Meikle
authors.forename: G
authors.initials: G
authors.lastname: El-Fakhri
authors.forename: Z
authors.initials: Z
authors.lastname: Kuncic
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use*; D002467:Cell Nucleus / Q000528:radiation effects; D004249:DNA Damage; D006801:Humans; D008297:Male; D015233:Models, Statistical; D009010:Monte Carlo Method; D011868:Radioisotopes / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D011883:Radium / Q000627:therapeutic use*
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; C581106:radium Ra 223 dichloride; D011883:Radium