Document Type : Original Research


1 PhD, Department of Medical Physics, Mashhad University of Medical Sciences, Mashhad, Iran

2 PhD, Department of Physics, Faculty of Rajaee, Quchan Branch, Technical and Vocational University (TVU), Khorasan Razavi, Iran

3 PhD, Medical Physics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran


Background: The importance of cellular dosimetry in both diagnostic and radiation therapy is becoming increasingly recognized.
Objective: This study aims to compare surviving fractions, which were predicted using Geant4 and contained three types of cancer cell lines exposed to 188Re with the experimentally surviving fraction determined by MTT assay.
Material and Methods: In this comparative study, Geant4 was used to simulate the transport of electrons emitted by 188Re from the cell surface, cytoplasm, nucleus or medium around the cells. The nucleus dose per decay (S-value) was computed for models of single cell and random monolayer cell. Geant4-computed survival fraction (SF) of cancer cells exposed to 188Re was compared with the experimental SF values of MTT assay.
Results: For single cell model, Geant4 S-values of nucleus-to-nucleus were consistent with values reported by Goddu et al. (ratio of S-values by analytical techniques vs. Geant4 = 0.811–0.975). Geant4 S-values of cytoplasm and cell surface to nucleus were relatively comparable to the reported values (ratio =0.914–1.21). For monolayer model, the values of SCy→N and SCS→N, were greater compared to those for model of single cell (2%–25% and 4%–38% were larger than single cell, respectively). The Geant4 predicted SF for monolayer MCF7, HeLa and A549 cells was in agreement with the experimental data in 10μCi activity (relative error of 2.29%, 2.69% and 2.99%, respectively).
Conclusion: Geant4 simulation with monolayer cell model showed the highest accuracy in predicting the SF of cancer cells exposed to homogeneous distribution of 188Re in the medium.


  1. Chatal J-F, Hoefnagel CA. Radionuclide therapy. Lancet. 1999;354:931-5.
  2. Schell S, Wilkens JJ, Oelfke U. Radiobiological effect based treatment plan optimization with the linear quadratic model. Z Med Phys. 2010;20:188-96. doi: 10.1016/j.zemedi.2010.02.003. PubMed PMID: 20832006.
  3. Bousis C, Emfietzoglou D, Nikjoo H. Monte Carlo single-cell dosimetry of I-131, I-125 and I-123 for targeted radioimmunotherapy of B-cell lymphoma. Int J Radiat Biol. 2012;88:908-15. doi: 10.3109/09553002.2012.666004. PubMed PMID: 22348681.
  4. Bardies M, Chatal JF. Absorbed doses for internal radiotherapy from 22 beta-emitting radionuclides: beta dosimetry of small spheres. Phys Med Biol. 1994;39:961-81. doi: 10.1088/0031-9155/39/6/004. PubMed PMID: 15551573.
  5. Humm JL. Dosimetric aspects of radiolabeled antibodies for tumor therapy. J Nucl Med. 1986;27:1490-7. PubMed PMID: 3528417.
  6. Humm JL. A microdosimetric model of astatine-211 labeled antibodies for radioimmunotherapy. Int J Radiat Oncol Biol Phys. 1987;13:1767-73. doi: 10.1016/0360-3016(87)90176-3. PubMed PMID: 3667382.
  7. Emfietzoglou D, Bousis C, Hindorf C, Fotopoulos A, Pathak A, Kostarelos K. A Monte Carlo study of energy deposition at the sub-cellular level for application to targeted radionuclide therapy with low-energy electron emitters. Nucl Instrum Methods Phys Res B. 2007;256:547-53.
  8. Bousis C, Emfietzoglou D, Hadjidoukas P, Nikjoo H. A Monte Carlo study of absorbed dose distributions in both the vapor and liquid phases of water by intermediate energy electrons based on different condensed-history transport schemes. Phys Med Biol. 2008;53:3739-61. doi: 10.1088/0031-9155/53/14/003. PubMed PMID: 18574312.
  9. Bernal MA, Liendo JA. An investigation on the capabilities of the PENELOPE MC code in nanodosimetry. Med Phys. 2009;36:620-5. doi: 10.1118/1.3056457. PubMed PMID: 19292002.
  10. Syme AM, Kirkby C, Riauka TA, Fallone BG, McQuarrie SA. Monte Carlo investigation of single cell beta dosimetry for intraperitoneal radionuclide therapy. Phys Med Biol. 2004;49:1959-72. doi: 10.1088/0031-9155/49/10/009. PubMed PMID: 15214535.
  11. Cai Z, Pignol J-P, Chan C, Reilly RM. Cellular dosimetry of 111In using Monte Carlo N-particle computer code: comparison with analytic methods and correlation with in vitro cytotoxicity. J Nucl Med. 2010;51:462-70. doi: 10.2967/jnumed.109.063156.
  12. Cai Z, Kwon YL, Reilly RM. Monte Carlo N-Particle (MCNP) Modeling of the Cellular Dosimetry of 64Cu: Comparison with MIRDcell S Values and Implications for Studies of Its Cytotoxic Effects. J Nucl Med. 2017;58:339-45. doi: 10.2967/jnumed.116.175695. PubMed PMID: 27660146.
  13. Nikjoo H, Uehara S, Emfietzoglou D, Cucinotta F. Track-structure codes in radiation research. Radiat Meas. 2006;41:1052-74. doi: 10.1016/j.radmeas.2006.02.001.
  14. Agostinelli S, Allison J, Amako Ka, Apostolakis J, Araujo H, Arce P, et al. GEANT4—a simulation toolkit. Nucl Instrum Methods Phys Res A. 2003;506:250-303.
  15. Allison J, Amako K, Apostolakis J, Araujo H, Dubois PA, Asai M, et al. Geant4 developments and applications. IEEE Trans Nucl Sci. 2006;53:270-8.
  16. Chauvie S, Francis Z, Guatelli S, Incerti S, Mascialino B, Montarou G, et al., editors. Models of biological effects of radiation in the Geant4 Toolkit. IEEE Nuclear Science Symposium Conference Record; San Diego, Calif: IEEE Service Center; 2006.
  17. Kyriakou I, Emfietzoglou D, Ivanchenko V, Bordage M, Guatelli S, Lazarakis P, et al. Microdosimetry of electrons in liquid water using the low-energy models of Geant4. J Appl Phys. 2017;122:024303. doi: 10.1063/1.4992076.
  18. Cirrone GP, Cuttone G, Mazzaglia SE, Romano F, Sardina D, Agodi C, et al. Hadrontherapy: a Geant4-based tool for proton/ion-therapy studies. Prog Nucl Sci Technol. 2011;2:207-12. doi: 10.15669/pnst.2.207.
  19. Sefl M, Incerti S, Papamichael G, Emfietzoglou D. Calculation of cellular S-values using Geant4-DNA: The effect of cell geometry. Appl Radiat Isot. 2015;104:113-23. doi: 10.1016/j.apradiso.2015.06.027. PubMed PMID: 26159660.
  20. Jiang RD, Shen H, Piao YJ. The morphometrical analysis on the ultrastructure of A549 cells. Rom J Morphol Embryol. 2010;51:663-7. PubMed PMID: 21103623.
  21. Arya SK, Lee KC, Bin Dah’alan D, Daniel, Rahman AR. Breast tumor cell detection at single cell resolution using an electrochemical impedance technique. Lab Chip. 2012;12:2362-8. doi: 10.1039/c2lc21174b. PubMed PMID: 22513827.
  22. Zhao L, Sukstanskii AL, Kroenke CD, Song J, Piwnica-Worms D, Ackerman JJ, et al. Intracellular water specific MR of microbead-adherent cells: HeLa cell intracellular water diffusion. Magn Reson Med. 2008;59:79-84. doi: 10.1002/mrm.21440. PubMed PMID: 18050315. PubMed PMCID: PMCPMC2730972.
  23. Chen KT, Lee TW, Lo JM. In vivo examination of (188)Re(I)-tricarbonyl-labeled trastuzumab to target HER2-overexpressing breast cancer. Nucl Med Biol. 2009;36:355-61. doi: 10.1016/j.nucmedbio.2009.01.006. PubMed PMID: 19423002.
  24. Carlone M, Wilkins D, Raaphorst P. The modified linear-quadratic model of Guerrero and Li can be derived from a mechanistic basis and exhibits linear-quadratic-linear behaviour. Phys Med Biol. 2005;50:L9-13. doi: 10.1088/0031-9155/50/10/l01. PubMed PMID: 15876677.
  25. Goddu SM. MIRD Cellular S values: Self-absorbed dose per unit cumulated activity for selected radionuclides and monoenergetic electron and alpha particle emitters incorporated into different cell compartments. Reston: Society of Nuclear Medicine; 1997.
  26. Qing Y, Yang X-Q, Zhong Z-Y, Lei X, Xie J-Y, Li M-X, et al. Microarray analysis of DNA damage repair gene expression profiles in cervical cancer cells radioresistant to 252 Cf neutron and X-rays. BMC Cancer. 2010;10:71. doi: 10.1186/1471-2407-10-71.
  27. Lacoste-Collin L, Castiella M, Franceries X, Cassol E, Vieillevigne L, Pereda V, et al. Nonlinearity in MCF7 Cell Survival Following Exposure to Modulated 6 MV Radiation Fields: Focus on the Dose Gradient Zone. Dose Response. 2015;13:1559325815610759. doi: 10.1177/1559325815610759. PubMed PMID: 26740805. PubMed PMCID: PMCPMC4679192.
  28. Jiang L, Xiong XP, Hu CS, Ou ZL, Zhu GP, Ying HM. In vitro and in vivo studies on radiobiological effects of prolonged fraction delivery time in A549 cells. J Radiat Res. 2013;54:230-4. doi: 10.1093/jrr/rrs093. PubMed PMID: 23090953. PubMed PMCID: PMCPMC3589931.