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Apr 1 – 5, 2019
Fairmont Château Laurier Hotel
UTC timezone

In vitro radiobiological effects of Radium-223

Not scheduled
Fairmont Château Laurier Hotel

Fairmont Château Laurier Hotel



Mr Francisco Liberal (Queen's University Belfast)


α-particle emitting radionuclides have been increasingly used in cancer treatment with particular interest for the treatment of micrometastases, due to the recently demonstrated survival benefit of Radium-223 (223Ra) in the treatment of bone metastases [1]. However, the reasons for its efficacy in comparison to previous beta emitters remains poorly understood. There is a pressing need to model and quantify α-emitter effects in pre-clinical models so the next generation of trials utilizing 223Ra can be optimally designed. It is often assumed that the higher lethality of α-particles is related with the higher propensity for complex DNA double-strand breaks (DBSs) and clustered DNA damage in the irradiated cells. The present investigation was carried out to evaluate the radiobiological effect of 223Ra in 3 different prostate cell models (PC-3, U-2OS metastatic lines, and normal RWPE) by assays of clonogenic survival and DNA damage. Clonogenic cell survival curves were analyzed for different cell lines after irradiation with 225 kVp X-rays from 0 to 8 Gy (dose rate 0.594 Gy/min), external α-particles (241 Americium) from 0 to 2 Gy (dose rate 1.579 Gy/min) and 223Ra from 0 to 0.5 Gy (dose rate 1.389 mGy/min). The results showed a superior efficacy of 223Ra in comparison with the external α source in all cell lines but with a cell type dependency. The Relative Biological Effectiveness (RBE) for 50% survival for RWPE is 6.07 and 7.97, for external α- particles and 223Ra respectively. For U-2OS is 6.36 and 8.9 and finally for PC-3 the values are 3.63 and 7.47. Lastly, the induction and repair of DNA damage by different radiation qualities was analyzed by immunofluorescence (53BP1) for doses up to 2 Gy and recovery times of 1, 4, 24 and 96h. For all irradiation setups there is a linear relationship between the number of foci and the absorbed dose. The level of induction and the shape of the kinetics curves are radiation- and cell-specific with the highest induction of foci observed after X-ray irradiation, the lowest after external α irradiation, and 223Ra being slightly higher than external α particles. In terms of repair, foci induced by external α source or 223Ra are repaired approximately 3.5 times slower than the X-ray induced breaks in the same cell line. These observations support the higher propensity for complex DNA-damage induced by heavy particles as reported in the literature. Interestingly, exposure to 223Ra severely affects the nuclear structure with a significant number of giant nuclei, and a large fraction of cells undergoing mitotic catastrophe, features not seem to the same extent with external beam irradiation. In conclusion, our results suggest that response to Radium-223 is cell-specific and that better effectiveness does not solely depend on the DNA damage complexity. [1] Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213-223.
Funding Agency Fundação para a Ciência e Tecnologia (FCT-MCTES) and Movember/Prostate Cancer UK
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Presentation Type Contributed Oral

Primary author

Mr Francisco Liberal (Queen's University Belfast)


Mr Hugo Moreira (Queen's University Belfast) Prof. Joe O'Sullivan (Queen's University Belfast) Dr Kelly Redmond (Queen's University Belfast) Prof. Kevin Prise (Queen's University Belfast) Dr Stephen McMahon (Queen's University Belfast)

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