Cell scale 125I microdosimetry

The full text of the publication follows. The aim of this study is to derive microdosimetric data from 125I Auger electron irradiation at cellular and subcellular scales within the context of Radioimmunotherapy (RIT). 125I decays through electronic capture and internal conversion processes, resulting in the emission of Auger electron cascades at the end of the process. The energy of 125I Auger electrons is mainly between some eV and 1 keV, resulting in a short path length in biological matter (from about 2 nm to 500 nm) when compared to average cell dimensions. Preclinical cell experiments performed at IRCM [1][2] showed strong differences in cellular response depending on the position of 125I labeled antibodies. This may be due to large statistical fluctuations of energy deposition within the target cell and, consequently, within radiosensitive organelles like nucleus, membrane or mitochondria. To understand the fundamental mechanisms of radiation damage at the cellular scale in the context of RIT, we decided to use Monte-Carlo methods to give account of the stochastic nature of energy deposition from Auger electrons at the subcellular scale. The first part of our study will compare three Monte-Carlo codes at low energy electrons: -) Geant4DNA, a recent extension of the general Monte-Carlo code Geant4 for very low energies, from a few eV to TeV [3]; -) CPA100, a step-by-step Monte-Carlo code developed by Terrissol in Toulouse down to 10 eV [4]; -) PENELOPE version 2008.1 for energies from 50 eV to 1 GeV [5]. Then, realistic cells and sources configurations will be modeled for a realistic 125I Auger electron emission spectrum in Geant4DNA in order to derive microdosimetric parameters such as specific or lineal energy. References: [1] Pouget J.P., Santoro L., Raymond L., Chouin N., Bardies M., Bascoul-Mollevi C., Huguet H., Azria D., Kotzki P.O., Pelegrin M., Vives E. and Pelegrin A., 'Cell membrane is a more sensitive target than cytoplasm to dense ionization produced by Auger electrons', Radiat. Res., vol. 170(2), p. 192-200 (2008); [2] Santoro L., Boutaleb S., Garambois V., Bascoul-Mollevi C., Boudousq V., Kotzki P.O., Pelegrin M., Navarro-Teulon I., Pelegrin A., Pouget J.P., 'Non-internalizing monoclonal antibodies are suitable candidates for 125I radioimmunotherapy of small-volume peritoneal carcinomatosis', J. Nucl Med, vol. 50(12), p. 2033-2041 (2009); [3] Chauvie S., Francis Z., Guatelli S., Incerti B., Mascialino B., Moretto P., Nieminen P., Pia M.G., 'Geant4 Physics Processes for Microdosimetry Simulation: Design Foundation and Implementation of the First Set of Models', IEE Trans. Nucl. Sc., vol.54(6), P. 2619-2628 (2007); [4] Terrissol M., Beaudre A., 'Simulation of space and time evolution of radiolytic species induced by electrons in water', Rad. Prot. Dos., vol.31(1), p.175-177 (1990); [5] Baro J., Sempau J., Fernandez-Varea J.M., Salvat F., 'PENELOPE: An algorithm for Monte Carlo simulation of the penetration and energy loss of electrons and positrons in matter', Nucl. Instr. And Meth. Phys. Res., vol.100(1), p.31-46 (1995). (authors)