Monte Carlo single-cell dosimetry of Auger-electron emitting radionuclides

Bousis, C.; Emfietzoglou, Dimitris; Hadjidoukas, Panagiotis E.; Nikjoo, Hooshang

doi:10.1088/0031-9155/55/9/009

Cited by 48 publications

(45 citation statements)

References 74 publications

(93 reference statements)

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“…Since the opposite sides are the same, we will Table 3 Radionuclide cellular S-values for spherical geometry (cell radius 5 μm; nucleus radius 4 μm). MIRD data are taken from (Goddu et al, 1997) data calculated using in-house Monte Carlo code MC4 from (Bousis et al, 2010) data calculated by code ETRAC are taken from (Ftáčniková and Böhm, 2000). The statistical uncertainty of all values corresponding to 1s is below 1%.…”

Section: Energy [Kev] S(c'c) [Gy/bq/s] S(c'cs) [Gy/bq/s] S(n'n) [Gy/bmentioning

confidence: 99%

“…1 8 E À 4 2.53E À 4 MC4 (Bousis et al, 2010) 3.71E À 3 2.01E À 3 6.87E À 3 6.94E À 4 4 . 1 8 E À 4 ETRAC (Ftáčniková and Böhm, 2000) 3.34E À 3 1.80E À 3 6.25E À 3 6.37E À 4 3 .…”

Section: S(c'c) [Gy/bq/s] S(c'cs) [Gy/bq/s] S(n'n) [Gy/bq/s] S(n'cy) unclassified

“…Specifically, differences between the convolution integral and the Monte Carlo results were up to 50% for the largest sphere (radius 1 μm), increasing further for smaller spheres. Bousis et al (Bousis, 2011;Bousis et al, 2012Bousis et al, , 2010 have tabulated cellular S-values using their home-made Monte Carlo code (MC4) for various Auger-emitting radionuclides, reporting good agreement ( $ 10%) with MIRD for S(C'C), S (C'CS) and S(N'N) but poor agreement ( $ 50%) for S(N'Cy) and S(N'CS) (C: cell, CS: cell surface, N: nucleus, Cy: cytoplasm). Champion et al (2008) used the Monte Carlo code CELLDOSE to calculate S-values in water spheres with radius from 50 nm to 2.5 mm for I-131.…”

Section: Introductionmentioning

confidence: 99%

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Calculation of cellular S-values using Geant4-DNA: The effect of cell geometry

Šefl

Incerti

Papamichael

et al. 2015

Applied Radiation and Isotopes

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Section: Energy [Kev] S(c'c) [Gy/bq/s] S(c'cs) [Gy/bq/s] S(n'n) [Gy/bmentioning

confidence: 99%

Section: S(c'c) [Gy/bq/s] S(c'cs) [Gy/bq/s] S(n'n) [Gy/bq/s] S(n'cy) unclassified

Section: Introductionmentioning

confidence: 99%

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Calculation of cellular S-values using Geant4-DNA: The effect of cell geometry

Šefl

Incerti

Papamichael

et al. 2015

Applied Radiation and Isotopes

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“…5 Auger-electron emitting (AE) radionuclides (e.g., 125 I, 67 Ga, 111 In, 99m Tc, 123 I, 201 Tl) can induce extreme cellular toxicity, thereby enhancing therapeutic efficacy, in a way similar to high linear energy transfer (LET) ionizing radiation; however, their applications are limited by the precondition for decays to occur within or in close proximity to vital biomolecules (e.g., DNA). [6][7][8][9] Despite this limitation that requires a sophisticated carrier system, AE radionuclides have been suggested as a promising therapeutic approach for treating numerous cancers, particularly for the treatment of single-cell metastatic cancers, leukemia and disseminated diseases. [10][11][12][13] AE radionuclides mainly decay via internal conversion and/or electron capture, which result in the emission of a cascade of electrons, including Auger, Coster-Kronig, and super Costerkronig electrons (generally termed Auger electrons), and characteristic x rays with energies between a few eV and 1 keV.…”

Section: Introductionmentioning

confidence: 99%

Correlation between energy deposition and molecular damage from Auger electrons: A case study of ultra-low energy (5-18 eV) electron interactions with DNA

2014

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Purpose-The present study introduces a new method to establish a direct correlation between biologically related physical parameters (i.e., stopping and damaging cross sections, respectively) for an Auger-electron emitting radionuclide decaying within a target molecule (e.g., DNA), so as to evaluate the efficacy of the radionuclide at the molecular level. These parameters can be applied to the dosimetry of Auger electrons and the quantification of their biological effects, which are the main criteria to assess the therapeutic efficacy of Auger-electron emitting radionuclides.Methods-Absorbed dose and stopping cross section for the Auger electrons of 5-18 eV emitted by 125 I within DNA were determined by developing a nanodosimetric model. The molecular damages induced by these Auger electrons were investigated by measuring damaging cross section, including that for the formation of DNA single-and double-strand breaks. Nanoscale films of pure plasmid DNA were prepared via the freeze-drying technique and subsequently irradiated with low-energy electrons at various fluences. The damaging cross sections were determined by employing a molecular survival model to the measured exposure-response curves for induction of DNA strand breaks.Results-For a single decay of 125 I within DNA, the Auger electrons of 5-18 eV deposit the energies of 12.1 and 9.1 eV within a 4.2-nm 3 volume of a hydrated or dry DNA, which results in the absorbed doses of 270 and 210 kGy, respectively. DNA bases have a major contribution to the deposited energies. Ten-electronvolt and high linear energy transfer 100-eV electrons have a similar cross section for the formation of DNA double-strand break, while 100-eV electrons are twice as efficient as 10 eV in the induction of single-strand break.Conclusions-Ultra-low-energy electrons (<18 eV) substantially contribute to the absorbed dose and to the molecular damage from Auger-electron emitting radionuclides; hence, they should be considered in the dosimetry calculation of such radionuclides. Moreover, absorbed dose is not an appropriate physical parameter for nanodosimetry. Instead, stopping cross section, which describes the probability of energy deposition in a target molecule can be an appropriate nanodosimetric parameter. The stopping cross section is correlated with a damaging cross section a)Author to whom correspondence should be addressed. CIHR Author ManuscriptCIHR Author Manuscript CIHR Author Manuscript (e.g., cross section for the double-strand break formation) to quantify the number of each specific lesion in a target molecule for each nuclear decay of a single Auger-electron emitting radionuclide.

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“…Historically TRT has been based mainly on semi-empirical formulas and techniques to determine radiation doses [7]. Only recently were dose calculations based on elementary processes presented and entered practical applications [8,9]. Therefore, correct experimental and theoretical cross section (SC) data for [10][11][12][13][14][15] LEEs' interaction with biomolecules are essential for such calculations, so as to provide not only the deposited energy and damage distributions within a cell, but also to link more directly these distributions to the RBE [16].…”

Section: Introductionmentioning

confidence: 99%

Nanodosimetry of Auger electrons: A case study from the decay of125I and 0–18-eV electron stopping cross sections of cytosine

2013

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Radiopharmaceuticals emitting Auger electrons are often injected into patients undergoing cancer treatment with targeted radionuclide therapy (TRT). In this type of radiotherapy, the radiation source is radial and most of the emitted primary particles are low-energy electrons (LEEs) having kinetic energies distributed mostly from zero to a few hundred electron volts with very short ranges in biological media. These LEEs generate a high density of energy deposits and clustered damage, thus offering a relative biological effectiveness comparable to that of alpha particles. In this paper, we present a simple model and corresponding measurements to assess the energy deposited near the site of the radiopharmaceuticals in TRT. As an example, a calculation is performed for the decay of a single 125 I radionuclide surrounded by a 1-nm-radius spherical shell of cytosine molecules using the energy spectrum of LEEs emitted by 125 I along with their stopping cross sections between 0 and 18 eV. The dose absorbed by the cytosine shell, which occupies a volume of 4 nm 3 , is extremely high. It amounts to 79 kGy per decay of which 3%, 39%, and 58% is attributed to vibrational excitations, electronic excitations, and ionization processes, respectively.

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Monte Carlo single-cell dosimetry of Auger-electron emitting radionuclides

Cited by 48 publications

References 74 publications

Calculation of cellular S-values using Geant4-DNA: The effect of cell geometry

Calculation of cellular S-values using Geant4-DNA: The effect of cell geometry

Correlation between energy deposition and molecular damage from Auger electrons: A case study of ultra-low energy (5-18 eV) electron interactions with DNA

Nanodosimetry of Auger electrons: A case study from the decay of125I and 0–18-eV electron stopping cross sections of cytosine

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