Stochastic simulation of radium-223 dichloride therapy at the sub-cellular level. (27th July 2015)

• Record Type: Journal Article
• Authors: Gholami, Y; Zhu, X; Fulton, R; Meikle, S; El-Fakhri, G; Kuncic, Z
• Is Part Of: Physics in medicine & biology. Volume 60:Number 15(2015:Aug.)
• Page Start: 6087
• Page End: 6096
• Publication Date: 2015-07-27
• Subjects: radionuclide therapy -- Monte Carlo modelling -- radium-223 dichloride; Biophysics -- Periodicals; Medical physics -- Periodicals; 610.153
• DOI: 10.1088/0031-9155/60/15/6087
• Languages: English
• ISSNs: 0031-9155

Abstract

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 ( 40%) can be attributed in part to the variation in LET with pathlength. We also found that 18% of cell nuclei receive less than one sigma below the average dose per cell ( 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.