Brachytherapy
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(2020)
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An in silico study on the effect of host tissue at brachytherapy dose
enhancement by gold nanoparticles
Samaneh Hashemi1, Seyed Mahmoud Reza Aghamiri1,*, Ramin Jaberi2, Zahra Siavashpour3
1
Medical Radiation Department, Shahid Beheshti University, Tehran, Iran
2
Cancer Institute, Imam Khomeini Hospital, Tehran, Iran
3
Radiotherapy Oncology Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran
ABSTRACT
PURPOSE: Iridium-192 brachytherapy dose enhancement by gold nanoparticles was investigated
in five different tumor tissues to observe the tissue-related differences as an effective environmental
factor in the applications of nanoparticles as radio-enhancer agents.
METHODS AND MATERIALS: The brachytherapy high-dose-rate source of BEBIG Ir-192, a
tumor volume with five different tissues including water, Plexiglas, soft tissue, adipose, and bone
with and without a uniform distribution of gold nanoparticles were mimicked by MCNPX Monte
Carlo simulation code using lattice feature. Dose enhancement factors in the tumor volume were
measured separately regarding the types of tissue, and a previous study using GEometry ANd
Tracking 4 simulation was used for result validation.
RESULTS: The results demonstrated that various types of tissue, as the host of gold nanoparticles,
lead to different dose enhancement level, so that the bone and adipose have the lowest and the highest amount of dose enhancement factor with values 20.8% and 39.75%, respectively. The maximum
difference of 4.8% was achieved from data benchmarking.
CONCLUSIONS: The results of this study indicate that the MCNPX code can be used as a valid
tool for dose measurement in the presence of nanoparticles. Moreover, tissue types of tumor as an
environmental feature, alongside with the nanoparticle’s size and concentration as well as the conditions of radiotherapy, should be considered in the dose calculation. Ó 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Keywords:
Gold nanoparticles; Ir-192 brachytherapy; Tumor tissues; Monte Carlo simulation; Dose enhancement
1. Introduction
In material science, ultrafine particles with a size of 1e
100 nm are recognized as nanoparticles (NPs). Because of
the size-related properties of NPs, many studies are conducted on them, particularly the applications in medicine,
optics, and electronics (1). In radiotherapy, as a branch of
medicine, the high atomic number of NPs has attracted a
lot of interest because of their capacity to enhance the radiation damage (2e5). Because the purpose of radiotherapy
is to deliver the maximum dose to the target volume and
the minimum to the normal surrounding tissues, injection
Received 15 May 2020; received in revised form 14 September 2020;
accepted 17 October 2020.
Disclosures: The authors declare that there is no conflict of interest.
* Corresponding author. Medical Radiation Engineering Department,
Shahid Beheshti University, Velenjak, Tehran, Iran. Tel: þ98-912-4117233; fax: þ98 21 29904210.
E-mail address: smr-aghamiri@sbu.ac.ir (S.M.R. Aghamiri).
of heavy NPs in the tumor can selectively increase the possibility of enhancing the radiation damage in the tumor and
therefore improve the results of treatment (6). The special
property of heavy NPs has related to increasing the electron
production inside the target, which releases as a result of radiation interaction with NPs (7e9). The dose enhancement
effect on the target volume due to the interaction between
the high-energy beam with the NPs has been studied in
many articles (10e18). In the simulation studies, two
Monte Carlo (MC) codes of the Monte Carlo N-particle
(MCNP) and GEometry ANd Tracking 4 (Geant4) are the
most widely used simulation codes in the investigation of
NP properties during the irradiation. Using Geant4 code,
Leung et al. (19) studied the properties of secondary electrons produced by X-ray interaction with gold nanoparticles
(GNPs) and the dependence on the beam energy and the
size of NPs in a water medium. Brivio et al. (20) simulated
a new I-125 brachytherapy technique for a high-risk prostate cancer via injection of GNPs directly into the prostate.
1538-4721/$ - see front matter Ó 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.brachy.2020.10.014
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Fig. 1. Source of BEBIG Ir-192 modeled by the MCNPX code (the sizes are in mm and not to scale).
In a comparison study, Toossi et al. (21) investigated the
dose enhancement of gold and gadolinium NPs with the
brachytherapy sources like Au-198 and Ir-192; the MCNPX
code was used, and three concentrations of NPs were simulated in a phantom of soft tissue. Hwang et al. (22) studied
the effect of the NP’s sizes and concentrations and the energy of radiation beam on dose enhancement of radiotherapy. In this work, X-rays of a Clinac in various
energies, a cobalt machine, and a mathematical Snyder
head phantom were modeled by the MCNPX code.
In all the studies that have been carried out so far, some
special subjects or parameters have been always considered
on dose enhancement such as the type of the NP, its size,
and concentration, as well as radiation features like the radiation source, energy, and the radiation patterns, but the
type of tissue, as the host of NPs, can be a variable parameter in different cases. At the in silico or phantom studies,
water and Plexiglas are mainly used because of their similar
properties to soft tissue, including density and effective
atomic number, and in the clinical investigation, depending
on the tumor location, different body tissues can be the host
of NPs such as soft tissue, adipose, or the bones. Therefore,
in several situations, different tissues contain NPs. In this in
silico study, it was tried to investigate the effect of tissue
type containing GNPs on dose enhancement of Ir-192 as
a brachytherapy source.
2. Materials and methods
In this study, the MCNPX code was used, which is
developed by the Los Alamos International Laboratory in
the United States (23) and so far has been widely used in
a variety of radiation modeling such as medical, industrial,
and nuclear application. (24) NPs with different sizes can
be mimicked by the ‘‘lattice’’ feature of this code, which
was carried out in this work, and the results were compared
and benchmarked by the dosimetry values that reported
from the Geant4 simulation code in the previous study
(25). Dose measurement was performed by f6 tally of the
MCNPX code with transporting of 2)107 particles and an
uncertainty below 3%. Dose variation was calculated as
the dose enhancement factor (DEF) which is defined as
the dose ratio with to without GNP presence at a specific
point in a medium (see Eq. 1). To observe the effect of dose
enhancement on treatment time, dose and time is considered as a linear relationship based on the Qi and Deng study
(26) by the formula of D 5 aT with a 5 0.719313 E þ 01
Fig. 2. (a) A schematic of phantom, tumor, Ir-192 brachytherapy source and (b) The NP’s network and dosimetry voxels simulated by the MCNPX code.
(NP 5 nanoparticle).
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Table 1
Tissue composition (in percent) and their density
Element (atomic number) H (1) C (6) N (7) O (8) Na (11) Mg (12) P (15) S (16) Cl (17) K (19) Ca (20) Fe (26) I (53) Density (gr/cm3)
3.4
11.4
10.5
20
15
15.5
59.8
12.5
55
4.2
0.7
2.6
43.5
27.8
73.5
80
30
0.1
0.1
0.2
0.2
10.3
0.3
0.1
0.18
0.2
and R2 5 0.986 for Ir-192 source and in the dose ranging
0 to 140 Gy.
Dose with radiation þ GNPs
1 100
DEFð%Þ 5
Dose with radiation alone
ð1Þ
2.1 Source simulation
The brachytherapy high-dose-rate source of BEBIG Ir192 was modeled by the MCNPX code as it is illustrated
in Fig. 1. The active core containing Ir-192 is simulated
as a cylinder with 3.5 mm in height and 0.6 mm in diameter, which is located at the origin of a coordinate and in
the center of a spherical phantom. A concentric cylinder
with the active core is defined as the source capsule with
5.18 mm in height and 1 mm in diameter, which is made
of stainless steel with a density of 8.02 gr/cm3. All stainless
steel components were approximately considered of AISI
304 by the contribution of 2% Mn, 1% Si, 19% Cr, 10%
Ni, and 68% Fe. (27) The energy spectrum of Ir-192 was
obtained from the NuDat database (28), and irradiation
was considered in an isotropic manner.
2.2. Phantom simulation
Spherical phantom with a radius of 10 cm was defined
by the MCNPX code which encompassed the source in
the center. Tumor volume was modeled in the shape of a
cubic with dimensions of 1 1 1 cm3 which is located
at the radial distance of 1e2 cm from the source inside the
phantom. Figure 2 shows a schematic of simulated geometry in the MCNPX code. Some dosimetry voxels with dimensions of 2 2 2 mm3 were continuously defined
in the central axis of the Ir-192 source for dose calculation
which extended to a depth of 3 cm.
Five different material types of water, Plexiglas, soft tissue, adipose, and bone filled the phantom and the tumor
cell in the five separate simulation programs. The compositions of these materials are shown in Table 1. The results of
simulated water phantom were used for validation.
2.3. Gold nanoparticles
Grid tools and the ‘‘lattice’’ command in the MCNPX
code provide the possibility of NP simulation and a homogenous distribution with any diameter and concentration in a
medium. In this study, a tumor cell with a volume of
22.5
0.1
0.22
0.21
0.01
0.01
0.01
1.92
0.95
1.05
0.998
1.18
(29)
(29)
(29)
(25)
(30)
10 10 10 mm3 was divided into 1.0648 1013 cubic
with dimensions of 450 nm in which there are spherical
GNPs with a diameter of 100 nm. Therefore, a homogeneous distribution of GNPs provided in the tumor volume
and simulated a concentration of 9.7% by weight for the
GNP solution. The ratio of dose values in the dosimetry
voxels after and before NP introduction was used for calculation of the DEF.
3. Results
In the first step, the validation of the MCNPX simulations was investigated by reported results of a previous
study (25). Figure 3 shows the absorbed dose of the Ir192 brachytherapy source in the phantom before and after
introducing GNPs in this study. The comparison of the
simulation results is shown in Figs. 4 and 5, in the form
of normalized dose and DEF, respectively. Because of
different sizes of dosimetry voxels in two studies, dosimetry results were normalized between 0 and 1. As can be
seen, the results are in a good agreement, indicating the
reliability of the MCNPX code in the NP modeling. In
Fig. 5, DEFs versus distance from the source have investigated in two studies. The maximum relative difference was
4.86% for two sets of data.
1.0
Without GNP
With GNP
0.8
Normalized Dose
Bone
Adipose
Soft tissue
Water
Plexiglas
0.6
0.4
0.2
0.0
8
10
12
14
16
18
20
22
24
26
28
Distance from the source (mm)
Fig. 3. Ir-192 absorbed dose in the phantom before and after introducing
GNPs calculated by MCNPX in this study (Lines were fitted through the
data by R2 5 0.99). (GNPs 5 gold nanoparticles).
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b
1.0
1.0
Zhang study
Current study
0.8
Normalized Dose
0.8
Normalized Dose
Zhang study
Current study
0.6
0.4
0.2
0.6
0.4
0.2
0.0
0.0
8
10
12
14
16
18
20
22
24
26
8
10
12
Distance from the source (mm)
14
16
18
20
22
24
26
Distance from the source (mm)
Fig. 4. Dosimetry comparison between Geant4 in Zhang study and MCNPX in the present study: (a) without GNPs and (b) with GNPs (Lines were fitted
through the data by R2 5 0.99). (GNPs 5 gold nanoparticles).
In the second step and after confirming the results of the
simulation, the tissue of the phantom, as well as tumor, was
substituted by the other four materials of soft tissue
including bone, adipose, and Plexiglas during separate programs. The results related to the DEF are shown in Fig. 6.
In the presence of GNPs, adipose, soft tissue, water, Plexiglas, and bone have the highest dose improvement, respectively. The DEF values of the tumor for different types of
tissue are quantitatively presented in Table 2. Accordingly,
water and soft tissue with a DEF of 35.4% and 36.34%,
respectively, have the closest similarity, and adipose tissue
with 39.75% and bone with 20.8%, respectively, have the
highest and the lowest level of dose improvement when
they contain GNPs. A comparison of treatment time for
different host tissues, which is an important parameter for
therapy, is also shown in Table 2.
4. Discussion
Herein, it was tried to define various types of tumor tissue as the GNP host by using the MCNPX MC code and
investigated their effects on the dose variation of the Ir192 brachytherapy source. In this regard, the lattice feature
of the code was used for the homogeneous distribution of
spherical GNPs with 100 nm in diameters in a tumor volume. NP modeling as the form of an atomic mixture
within the medium was carried out in some previous
80
1.7
Dose Enhancement Factor
1.6
1.5
1.4
1.3
1.2
1.1
Bone
Plexiglas
Water
So Tissue
Adipose
70
Dose Enhancement Factor (%)
Zhang Study
Current Study
60
50
40
30
20
10
1.0
0
0.9
8
10
12
14
16
18
20
22
24
26
Distance from the source (mm)
Fig. 5. DEF comparison at the radial distance of Ir-192 source between
2 MC simulations code of MCNPX (present study) and Geant4 (Zhang
et al.). (DEF 5 dose enhancement factor; MC 5 Monte Carlo).
0
5
10
15
20
25
30
Distance from the source (mm)
Fig. 6. DEF (%) of GNPs at the radial distance of Ir-192 source for
different types of tissue. (GNPs 5 gold nanoparticles; DEF 5 dose
enhancement factor).
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Table 2
Quantitative dose values of the tumor, DEFs, and a comparison of treatment time for different tissues containing GNPs
Tissue types
D1
Dose without GNPs (MeV/g)
D2
Dose with GNPs (MeV/g)
DEFs (%)
Treatment timea
Bone
Soft Tissue
Adipose
Water
Plexiglas
7.36E-04
6.83E-04
6.77E-04
7.46E-04
7.21E-04
8.89E-04
9.31E-04
9.46E-04
1.01E-03
9.54E-04
20.80
36.34
39.75
35.40
32.26
0.83
0.73
0.72
0.74
0.76
T1
T1
T1
T1
T1
GNPs 5 gold nanoparticles; DEFs 5 dose enhancement factors.
a
T1 is the time of brachytherapy for D1, and treatment time is reported for a constant dose.
articles (31e34), but Zhang (25) has proved that GNP
introduction in a water medium as the form of a goldwater mixture can cause the overestimation of dose measurement up to 16%. Therefore, in this study, GNPs were
simulated as the form of nanospheres for more similarity
to the real situation and to achieve more precise data.
Figures 4 and 5 show the results benchmark with the Zhang
study in the case of a water phantom. In the mentioned
study, dosimetry was performed by the Geant4 MC code
in comparison with the MCNPX in the current work. Data
of some points just near the source did not consider in both
studies because of the high-dose gradient around the source
for better illustration of the dose variation by the GNPs in
the tumor target. The good agreement between the results
of two studies and the maximum difference of 4.8% represents that MCNPX has the acceptable ability to NP
modeling in the arbitrary size and concentration.
DEFs for GNPs in five tissue types were presented in
Fig. 6. In several studies or different clinical cases, the location of NP accumulation depends on the tumor tissue. For
example, dose improvement was investigated in the water
by Toossi (21), in the soft tissue by Leung (19), and in
the head phantom by Hwang (22). Figure 5 demonstrates
that the NP host can be very effective on the tissue dose
enhancement, so that there is a relative difference of about
47% in the DEFs, for the materials used in this study, which
are water, Plexiglas, soft tissue, adipose, and bone. This
matter can directly affect treatment planning. The time of
brachytherapy with Ir-192 source, based on dose enhancement of different materials, is shown in Table 2. Because
treatment time is a parameter that can be changed by a
physician, it has an important role in dose calculation and
its application through the tumor volume. In accordance
with the results in Table 2, using GNPs can generally
reduce the time of brachytherapy by Ir-192. For a constant
dose, the time of dose delivery varies in the case of tumors
with different tissues, with a reduction of 27% achieved in
the case of adipose. This matter must be considered for
treatment planning. Spending the same treatment time,
for instance in the case of the adipose or bone, can lead
to delivering an overdose to the organs or inadequate dose
to a tumor apex, respectively.
In accordance with Table 2, the bone, with a higher
effective atomic number and density than the other existing
tissues, has the lowest amount of dose improvement with a
DEF of 20.8%. Besides, the adipose with the lowest density
and effective atomic number has the greatest effect of
GNPs’ presence with a DEF of 39.75%. The point is that
adding GNPs to an adipose medium impressively increases
the effective atomic number of the medium. Therefore,
dose enhancing of a photon beam will be noticeable. However, dose enhancement by GNPs will be less impressive in
the case of the bone with a higher effective atomic number.
In addition, the interaction mechanism of secondary electrons arising from irradiated GNPs is important, too. It is
shown that the ability to absorb energy from electron particles depends mainly on the number of absorbing electrons
in the path of the electrondthat is, on the areal density
(electrons/cm2) of electrons in the absorber and, to a much
lesser degree, on the atomic number of the absorber (35).
Therefore, because of hydrogen richness, adipose produces
an electron cloud at the photoelectron pathway and consequently, leads to an increase of the DEF rather than the
other tissue types.
Furthermore, the results of Table 2 again indicate that
water has a greater proximity to soft tissue in the DEF,
and therefore, it is the best material for radiation dosimetry
in the in vitro and in silico studies. While in the case of using Plexiglas instead of soft tissue, a difference about 11%
must be considered.
5. Conclusion
This study investigated the effect of various host tissues of
GNPs on tumor dose enhancement. It was achieved that dose
enhancement can be very different depending on the tumor
tissue type, which must be considered on the patient dose
calculation. This matter can help to increase the accuracy
of dose calculation in the presence of NPs and lead to choose
the optimum dose and to improve the treatment outcome.
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