Given the very short range (micrometers to few nanometers) of Auger electrons (AE), Coster-Kronig (CK) and internal conversion (IC) electrons emitted by several radionuclides, they are nowadays considered as promising solutions for molecular targeted radiotherapy. The aforementioned electrons can locally deposit their energy near the radionuclide decay site, reducing the radiotoxicity of the surrounding healthy tissues in this way. ¹²⁵I (T_1/2=59 days, 23 Auger electrons emitted per decay, Ē_Auger= 520 eV) and ^99mTc (T_1/2=6 h, 4.4 Auger electrons emitted per decay, Ē_Auger=213 eV) are two radionuclides that are largely studied for their potential use in theranostic, even if the effectiveness of the ^99mTc Auger emissions in inducing DNA double strand break (DSB) is still controversial. However, in recent years the use of ⁶⁴Cu (T_1/2=12.7 h, 1.80 Auger electrons emitted per decay, Ē_Auger=1134 eV) emerged and became a burning issue, because, in addition to its imaging capabilities, some studies showed that ⁶⁴Cu has cytotoxicity capabilities when incorporated in radiopharmaceuticals targeted at tumor cells. Therefore, for ⁶⁴Cu the accurate assessment of the energy deposition pattern near the radionuclide decay site and how this energy varies with the radionuclide-DNA center distance is of paramount importance in order to better design therapeutic strategies based on the Auger electrons emitted by this radionuclide. For this reason, the aim of this work is to study the absorbed dose in the DNA and cell volumes considering the aforementioned three radionuclides described above and for the different spectra emissions of A, CK, IC and β radiation. In order to reach these goals, the state-of-the-art Monte Carlo (MC) radiation transport program MCNP6 was used. For the modeling and simulation purposes, a simplified geometry for the DNA segment, the cytoplasm and the cell, composed of liquid water, was considered and an isotropic-like source was modeled. Emission data (photons were neglected) were obtained from the International Commission on radiological Protection (ICRP) publication ICRP-107. This study shows to what extent the deposited energy pattern distribution is affected when several spectra qualities are considered (Auger, Conversion and β emissions); the discussion and comparison of results (also in terms of S-values calculated in this work and reported by MIRD) obtained for ⁶⁴Cu with those obtained for ¹²⁵I and ^99mTc are reported.

1. R. W. Howell, “Auger processes in the 21^st century,” Int. J. Radiat. Biol., vol. 84, no. 12, pp. 959 – 975, Dec. 2008.
   DOI: 10.1080/09553000802395527
   PMid: 19061120
   PMCid: PMC3459331
2. P. L. Olive, “The role of DNA Single- and Double Strand Breaks in cell killing by Ionizing Radiation,” Radiat. Res., vol. 150, no. 5, pp. S42-S51, Nov. 1998.
   DOI: 10.2307/3579807
   PMid: 9806608
3. N. Falzone, J. M. Fernández-Varea, G. Flux, K. A. Vallis, “Monte Carlo Evaluation of Auger Electron–Emitting Theranostic Radionuclides,” J. Nucl. Med., vol. 56, no. 9, pp. 1441 – 1446, Sep. 2015.
   DOI: 10.2967/jnumed.114.153502
   PMid: 26205298
4. P. Balagurumoorthy et al., “Effect of distance between decaying ¹²⁵I and DNA on Auger electron induced double-strand break yield,” Int. J. Radiat. Biol., vol. 88, no. 12, pp. 998 – 1008, Dec. 2012.
   DOI: 10.3109/09553002.2012.706360
   PMid: 22732063
   PMCid: PMC3755766
5. A. N. Asabella et al., “The Copper Radioisotopes: A Systematic Review with Special Interest to ⁶⁴Cu,” BioMed Res. Int., vol. 2014, 786463, 2014.
   DOI: 10.1155/2014/786463
6. K. Eckerman et al., “ICRP Publication 107. Nuclear decay data for dosimetric calculations,” Ann. ICRP, vol. 38, pp. 7 – 96, 2008.
   PMid: 19285593
7. T. Goorley et al., “Initial MCNP6 release overview MCNP6 version 1.0,” Los Alamos National Laboratory, Los Alamos (NM), USA, Rep. LA-UR-13-22934, 2013.
   Retrieved from: http://permalink.lanl.gov/object/tr?what=info:lanl-repo/lareport/LA-UR-13-22934;
   Retrieved on: Aug. 7, 2017
8. G. Hughes, “Recent developments in low-energy electron/photon transport for MCNP6,” Prog. Nuc. Sci. Tech.,vol. 4, pp. 454 – 458, 2014.
   DOI: 10.15669/pnst.4.454
9. H. Nikjoo et al., “Track-structure codes in radiation research,” Radiat. Meas., vol. 41, no. 9-10, pp. 1052 – 1074, Oct-Nov. 2006.
   DOI: 10.1016/j.radmeas.2006.02.001
10. C. Champion et al., “Comparison between Three Promising ß-emitting Radionuclides, ⁶⁷Cu, ⁴⁷Sc and ¹⁶¹Tb, with Emphasis on Doses Delivered to Minimal Residual Disease,” Theranostics, vol. 6, no. 10, 2016.
    DOI: 10.7150/thno.15132
    PMid: 27446495
    PMCid: PMC4955060
11. S. M. Goddu, MIRD Cellular S-values, Reston (VA), USA: Society of Nuclear Medicine, 1997.
12. M. A. Tajik-Mansoury, H. Rajabi and H. Mazdarani, “A comparison between track-structure, condensed-history Monte Carlo simulations and MIRD cellular S-values,” Phys. Med. Biol., vol. 62, no. 5, pp. N90 – N106, Mar. 2017.
    DOI: 10.1088/1361-6560/62/5/N90
    PMid: 28181480
13. A. Taborda et al., “Dosimetry at the sub-cellular scale of Auger-electron emitter ^99mTc in a mouse single thyroid follicle,” Appl. Radiat. Isot., vol. 108, pp. 58 – 63, Feb. 2016.
    DOI: 10.1016/j.apradiso.2015.12.010
    PMid: 26704702
14. P. Lazakaris et al., “Comparison of nanodosimetric parameters of track structure calculated by the Monte Carlo codes Geant4-DNA and PTra,” Phys. Med. Biol.,vol. 57, no. 5, pp. 1231 – 1250, Mar.2012.
    DOI: 10.1088/0031-9155/57/5/1231
    PMid: 22330641
15. M. Dingfelder et al., “Comparisons of Calculations with PARTRAC and NOREC: Transport of Electrons in Liquid Water,” Radiat. Res., vol. 169, no. 5, pp. 584 – 594, May 2008.
    DOI: 10.1667/RR1099.1
    PMid: 18439039
    PMCid: PMC3835724
16. E. Pereira et al., “Evaluation of Acridine Orange Derivatives as DNA-Targeted Radiopharmaceuticals for Auger Therapy: Influence of the Radionuclide and Distance to DNA,” Sci. Rep., vol. 7, 42544, Feb. 2017.
    DOI: 10.1038/srep42544
17. L. Jiang et al., “In vitro and in vivo studies on radiobiological effects of prolonged fraction delivery time in A549 cells,” J. Radiat. Res., vol. 54, no. 2, pp. 230 – 234, Mar. 2013.
    DOI: 10.1093/jrr/rrs093
    PMid: 23090953
    PMCid: PMC3589931
18. J. F. Fowler et al., “Loss of biological effect in prolonged fraction delivery,” Int. J. Radiat. Oncol. Biol. Phys., vol. 59, no. 1, pp. 242 – 249, 2004.
    DOI: 10.1016/j.ijrobp.2004.01.004
    PMid: 15093921
19. J. Carlsson et al., “Requirements regarding dose rate and exposure time for killing of tumour cells in beta particle radionuclide therapy,” Eur. J. Nucl. Med. Mol. Imaging, vol. 33, no. 10, pp. 1185 – 1195, Oct. 2006.
    DOI: 10.1007/s00259-006-0109-3
    PMid: 16718515
    PMCid: PMC1998878