Cellular S-value of beta emitter radionuclide’s determined using Geant4 Monte Carlo toolbox, comparison to MIRD S-values

Document Type : Original Article


1 Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

2 Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran


Introduction: Spatial dose distribution around the radionuclides sources is required for optimized treatment planning in radioimmunotherapy. At present, the main source of data for cellular dosimetry is the s-values provided by MIRD. However, the MIRD s-values have been calculated based on analytical formula in which no electrons straggling is taken to account. In this study, we used Geant4-DNA Monte Carlo toolbox to calculate s-values and the results were compared to the corresponding MIRD data. Methods:Similar to MIRD cell model, two concentric spheres representing the cell and its nucleus were used as the geometry of simulation. The cells were assumed to be made of water. Cellular s-values were calculated for three beta emitter radionuclides 131I, 90Y and 177Lu that are widely used in radioimmunotherapy. Few lines of code in C++ were added into Geant4-DNA codes to automatically calculate the s-values and transfer data into excel files. Results:The differences between two series of data were analyzed using Pearson’s correlation and Bland-Altman curves. We observed high correlation (R2>0.99) between two series of data for self-absorption; however, the agreement was very weak and Wilcoxon signed rank test showed significant difference (p-value<0.001). In cross-absorption, Bland-Altman analysis showed a considerable bias between MIRD s-values and corresponding Geant4-DNA data. The percent differences between the data were -79% to +67%. Conclusion: Results of the comparison show a reflection of systematic error rather than statistical fluctuation. The inconsistency is most probably associated with the neglecting of straggling and δ-ray transport in MIRD analytical method.


Main Subjects

Chatal JF, Hoefnagel CA. Radionuclide therapy. Lancet. 1999 Sep 11;354(9182):931-5.
Dearling JL, Pedley RB. Technological advances in radioimmunotherapy. Clin Oncol (R Coll Radiol). 2007 Aug;19(6):457-69.
Buchsbaum DJ. Experimental radioimmunotherapy. Semin Radiat Oncol. 2000 Apr;10(2):156-67.
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 Dec;88(12):908-15.
Bardiès M, Myers MJ. Computational methods in radionuclide dosimetry. Phys Med Biol. 1996 Oct;41(10):1941-55.
Goddu SM, Rao DV, Howell RW. Multicellular dosimetry for micrometastases: dependence of self-dose versus cross-dose to cell nuclei on type and energy of radiation and subcellular distribution of radionuclides. J Nucl Med. 1994 Mar;35(3):521-30.
Humm JL. Dosimetric aspects of radiolabeled antibodies for tumor therapy. J Nucl Med. 1986 Sep;27(9):1490-7.
Bardiès M, Chatal JF. Absorbed doses for internal radiotherapy from 22 beta-emitting radionuclides: beta dosimetry of small spheres. Phys Med Biol. 1994 Jun;39(6):961-81.
Humm JL. A microdosimetric model of astatine-211 labeled antibodies for radioimmunotherapy. Int J Radiat Oncol Biol Phys. 1987 Nov;13(11):1767-73.
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 Meth B. 2007;256(1):547-53.
Budinger TF, Murty GS. 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, Va: Society of Nuclear Medicine; 1997.
Sgouros G. Dosimetry of internal emitters. J Nucl Med. 2005 Jan;46 Suppl 1:18S-27S.
Loevinger R, Budinger TF, Watson EE. MIRD primer for absorbed dose calculations. New York: Society of Nuclear Medicine; 1988.
Cole A. Absorption of 20-eV to 50,000-eV electron beams in air and plastic. Radiat Res. 1969 Apr;38(1):7-33.
Eckerman KF, Westfall RJ, Ryman JC, Cristy M. Nuclear decay data files of the dosimetry research group. ORNL/TM-12350. Oak Ridge, TN: Oak Ridge National Laboratory; 1993.
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 Jul 21;53(14):3739-61.
Bernal MA, Liendo JA. An investigation on the capabilities of the PENELOPE MC code in nanodosimetry. Med Phys. 2009 Feb;36(2):620-5.
Champion C, Zanotti-Fregonara P, Hindié E. CELLDOSE: a Monte Carlo code to assess electron dose distribution--S values for 131I in spheres of various sizes. J Nucl Med. 2008 Jan;49(1):151-7.
Emfietzoglou D, Kostarelos K, Hadjidoukas P, Bousis C, Fotopoulos A, Pathak A, Nikjoo H. Subcellular S-factors for low-energy electrons: a comparison of Monte Carlo simulations and continuous-slowing-down calculations. Int J Radiat Biol. 2008 Dec;84(12):1034-44.
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 May 21;49(10):1959-72.
Cai Z, Pignol JP, Chan C, Reilly RM. Cellular dosimetry of (111)In using monte carlo N-particle computer code: comparison with analytic methods and correlation with in vitro cytotoxicity. J Nucl Med. 2010 Mar;51(3):462-70.
Nikjoo H, Uehara S, Emfietzoglou D, Cucinotta FA. Track-structure codes in radiation research. Radiat Meas. 2006;41(9-10):1052-74.
Incerti S, Baldacchino G, Bernal M, Capra R, Champion C, Francis Z, Guatelli S, Gueye P, Mantero A, Mascialino B, Moretto P, Nieminen P, Rosenfeld A, Villagrasa C, Zacharatou C. The Geant4-DNA project. Int J Model Simul Sci Comput. 2010;1(02):157-78.
Eckerman KF, Endo A. MIRD: Radionuclide Data and Decay Schemes. Reston, Va: Society of Nuclear Medicine; 1989. 
Agostinelli S, Allison J, Amako Ka, Apostolakis J, Araujo H, Arce P, Asaig M, Axen D, Banerjee S, Barrand G, Behner F, Bellagamba L, Boudreau J, Broglia L, Brunengo A, Burkhardt H, Chauvie S, Chuma J, Chytracek R, Cooperman G, Cosmo G, Degtyarenko P, Dell'Acqua A, Depaola G, Dietrich D, Enami R, Feliciello A, Ferguson C, Fesefeldt H, Folger G, et al. GEANT4—a simulation toolkit. Nucl Instrum Meth A. 2003;506(3):250-303.
Incerti S, Ivanchenko A, Karamitros M, Mantero A, Moretto P, Tran HN, Mascialino B, Champion C, Ivanchenko VN, Bernal MA, Francis Z, Villagrasa C, Baldacchin G, Guèye P, Capra R, Nieminen P, Zacharatou C. Comparison of GEANT4 very low energy cross section models with experimental data in water. Med Phys. 2010 Sep;37(9):4692-708.
Francis Z, Incerti S, Karamitros M, Tran HN, Villagrasa C. Stopping power and ranges of electrons, protons and alpha particles in liquid water using the Geant4-DNA package. Nucl Instrum Meth B.  2011;269(20):2307-11.
Incerti S, Psaltaki M, Gillet P, Barberet P, Bardiès M, Bernal MA, Bordage MC, Breton V, Davidkova M, Delage E, El Bitar Z, Francis Z, Guatell S, Ivanchenko A, Ivanchenko V, Karamitros M, Lee SB, Maigne L, Meylan S, Murakami K, Nieminen P, Payno H, Perrot Y, Petrovic I, Pham QT, Ristic-Fira A, Santin G, Sasaki T, Seznec H, Shin JI, et al. Simulating radial dose of ion tracks in liquid water simulated with Geant4-DNA: A comparative study. Nucl Instrum Meth B. 2014;333:92-8.
André T, Morini F, Karamitros M, Delorme R, Le Loirec C, Campos L, Champion C, Groetz JE, Fromm M, Bordage MC, Perrot Y, Barberet Ph, Bernal MA, Brown JMC, Deleuze MS, Francis Z, Ivanchenko V, Mascialino B, Zacharatou C, Bardiès M, Incerti S. Comparison of Geant4-DNA simulation of S-values with other Monte Carlo codes. Nucl Instrum Meth B. 2014;319:87-94.
Champion C, Incerti S, Perrot Y, Delorme R, Bordage MC, Bardiès M, Mascialino B, Tran HN, Ivanchenko V, Bernal M, Francis Z, Groetz JE, Fromm M, Campos L. Dose point kernels in liquid water: an intra-comparison between GEANT4-DNA and a variety of Monte Carlo codes. Appl Radiat Isot. 2014 Jan;83 Pt B:137-41.
Bousis C, Emfietzoglou D, Hadjidoukas P, Nikjoo H. A Monte Carlo study of cellular S-factors for 1 keV to 1 MeV electrons. Phys Med Biol. 2009 Aug 21;54(16):5023-38.