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. 2021 Jan 11;55(2):86–95. doi: 10.1007/s13139-020-00680-5

Development of GATE Monte Carlo Code for Simulation and Dosimetry of New I-125 Seeds in Eye Plaque Brachytherapy

Payvand Taherparvar 1,✉, Zeinab Fardi 1
PMCID: PMC8053639  PMID: 33968275

Abstract

Purpose

Dose distributions are calculated by Monte Carlo (MC) simulations for two low-energy models 125I brachytherapy source—IrSeed-125 and IsoAid Advantage (model IAI-125A)—loaded in the 14-mm standardized plaque of the COMS during treatment of choroid melanoma.

Methods

In this study, at first, the radial dose function in water around 125I brachytherapy sources was calculated based on the recommendations of the Task Group No. 43 American Association of Physicists in Medicine (TG-43U1 APPM) using by GATE code. Then, brachytherapy dose distribution of a new model of the human eye was investigated for a 14-mm COMS eye plaque loaded with these sources with GATE Monte Carlo simulation.

Results

Results show that there are good agreements between simulation results of these sources and reporting measurements and simulations. Dosimetry results in the designed eye phantom for two types of iodine seeds show that the ratios of average dose of tumor to sclera, vitreous, and retina for IrSeed (IsoAid) source are 3.7 (3.7), 6.2 (6.1), and 6.3 (6.3), respectively, which represents the dose saving to healthy tissues. The maximum percentage differences between DVH curve of IsoAid and IrSeed seeds was about 8%.

Conclusions

Our simulation results show that although new model of the 125I brachytherapy source having a slightly larger dimension than IAI-125A, it can be used for eye melanoma treatment because the COMS eye plaque loaded with IrSeed-125 could produce similar results to the IsoAid seeds, which is applicable for clinical plaque brachytherapy for uveal melanoma.

Keywords: Ocular melanoma, Brachytherapy, Low-energy sources, GATE Monte Carlo

Introduction

More recent treatment modalities for ocular melanoma [1, 2] are brachytherapy, enucleation, transpupillary thermotherapy, and proton beam radiotherapy [3]. Today, brachytherapy with radioactive eye plaques and enucleation most commonly are used for treatment.

Brachytherapy is a special type of radiotherapy, in which an encapsulated beta [4] or gamma [5–7] source (radioactive seed) is placed within or close to a tumor inside the patient’s body [8, 9]. Brachytherapy using eye plaques loaded with the appropriate number of small sealed radioactive seeds (such as 125I, 103Pd, and 131Cs) have been increasingly used in recent years since this method of therapy is easily accessible and not expensive [10].

The selection of a suitable radionuclide for each specific treatment depends on the tumor size [11]; tumors with medium and large sizes are usually treated with applicators including 103Pd or 125I radioisotopes, whereas for the treatment of melanomas with small-to-medium sizes, 90Sr/90Y and 106Ru/106Rh beta-ray are common [12].

Different models of ophthalmic plaques such as the Collaborative Ocular Melanoma Study (COMS) standard, notched and modified designs, ROPES, USC, and IBt/Bebig (beta-emitters) are available for different types of eye tumors [11]. Low-energy sources for clinical treatment of ocular malignancies have been widely used in the COMS plaques which are accessible in seven standard sizes, with diameters ranging from 10 to 22 mm in 2-mm increments [13–15].

In the early studies, the eye plaque for clinical dose calculations is simulated at the center of a water phantom of length 300 mm with 0.998-g/cm3 density according to the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) formalism [16].

However, the constituent compounds and densities of eye materials differ in the various substructures of the human eye [14]. In order to estimate the accurate dose deposition within the tumour and normal tissues at risk, a complete model of the human eye with full anatomical details is required.

The various substructures of the eye (such as the sclera, choroid, retina, vitreous, anterior chamber, cornea, lens, and optic nerve) during treatment of uveal melanoma with brachytherapy received different dose levels. Among them, the lens is the most radiosensitive ocular structure [17]. Accordingly, in recent years, a lot of Monte Carlo simulations and experimental studies have been performed to evaluate dose distribution around COMS eye plaques containing various brachytherapy sources with different eye models.

In 2001, an experimental study for measurements of doses along the central-axis and off-axis dose profiles of 12 mm and 20 mm COMS plaques loaded with 125I seeds was performed in a water phantom by Knutsen et al. [18]. The acquired results were compared with doses calculated using the Plaque Simulator (IBt-Bebig, Berlin, Germany) software.

Krintz et al. in 2002 performed measurements using radiochromic (model MD55-2) film for 14-mm and 20-mm COMS plaques, fully loaded with 125I seeds (model 6711), in a solid water phantom. They measured the relative doses along the central- and off-axis profiles and compared their results with calculated dose distributions by Plaque Simulator software [13].

In 2005, Yoriyaz et al. designed a new mathematical eye model containing detailed descriptions of its components such as the sclera, choroid, retina, vitreous body, cornea, lens, anterior chamber, and optic nerve. Absorbed dose values due to ophthalmic plaques loaded with both 125I seeds and 60Co brachytherapy sources were obtained for different parts of the eye by MCNP-4C Monte Carlo code [19].

In 2009, Thomson et al. simulated 3D dose distributions in a homogenous water medium and eye phantom from specific 125I (model 6711) and 103Pd (model 200) sources in standard COMS plaques using BrachyDose code [20].

In 2010, based on BrachyDose Monte Carlo results, Thomson et al. presented a modified 22-mm COMS plaque with a 10-mm diameter which was loaded with 125I (model 6711) or 103Pd (model 200) seed circular cutout at the plaque center designed for the treatment of iris melanomas [21].

Zhang et al. also in 2010 simulated a 16-mm COMS plaque by MCNPX Monte Carlo code which was fully loaded with 125I seeds (IsoAid model IAI-125A) or 131Cs seeds (IsoRay model CS-1 Rev2) in a water equivalent insert without the silastic insert [22].

In 2014, Lesperance et al. investigate dosimetry for ocular brachytherapy for different eye plaque models loaded with 103Pd, 125I, and 131Cs seeds by using BrachyDose code in a voxelized eye model with detailed descriptions of internal structures [23].

In 2018, Ebrahimi and Vejdani estimated absorbed doses of the eye substructures for 12-mm COMS eye brachytherapy plaque, which loaded with 125I, 131Cs, and 103Pd seeds, based on MCNP4C simulation code, using the most realistic eye model [17].

In this study, by Monte Carlo simulations, we have evaluated the application of the new 125I brachytherapy source, which is known as IrSeed-125, in the 14-mm COMS standard eye plaque for clinical treatment of the ocular malignancies. The results have been compared with the IsoAid Advantage 125I model IAI-125A, which is commonly used in ophthalmic brachytherapy. In this way, at first, we validate and compare dosimetric parameters of these seeds, according to the TG-43U1 formalism in water phantom [24]. To investigate average delivered doses to the tumor and internal structures of the eye based on the literature review, a complete anatomic and voxelized human eye phantom was modeled. The eye model included a choroid melanoma with a height of 5 mm and largest basal diameter of 10 mm. These calculations have been performed using the GATE/Geant4 Monte Carlo code.

Materials and Methods

Eye Model Description

An adult human eyeball is composed of three layers, namely, retina, choroid, and sclera. It has an anterior-to-posterior diameter of 24 mm, whereas the vertical and lateral diameters are nearly 23 mm and 23.5 mm, respectively [19, 25]. Hence, we have considered a spherical shell of 24 mm as an eye globe, in the designed phantom. The eye model in the present study, as shown in Fig. 1, was constructed using concentric spheres which are nearly 1-mm thickness for the vitreous, retina, choroid, and sclera according to the Yoriyazʼs eye model [19].

Fig. 1.

Fig. 1

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Three sections (transverse, coronal, and sagittal) of the eye model and tumor in this study

The tumor has been designed with the apical height of 5 mm and the basal dimension of 10 mm, which is situated above the eye and on the inner surface of the sclera.

The lens volume, which is located at the posterior part of the anterior chamber, is defined as an ellipsoidal shape with 8 mm and 9 mm in equatorial diameters and 2.5 mm in polar diameter. Besides, the optic nerve is simulated as a cylindrical shell with diameters of 7 mm and 8 mm, which extends from the vitreous body to nearly 3 mm outside the eyeball. The geometric region bounded by the cornea inner wall and the anterior curved segment of the lens are known as the anterior chamber. The densities and chemical material composition of the tumor and organs which surround the tumor in eye phantom are given in Table 1 [25, 26].

Table 1.

Elemental compositions and densities of different parts of the human eye used in this study [25, 26]

Sclera Choroid Retina Vitreous Optic nerve Lens Cornea Tumor
H 9.6 9.4 9.4 11.0867 10.70 9.60 10.16 10.08
C 9.90 21.20 21.20 0.068 9.50 19.50 11.99 4.10
N 2.20 5.60 5.60 - 0.20 5.70 3.64 1.10
O 74.40 61.50 61.50 88.052 76.70 64.60 74.11 83.2
Na - 0.25 0.25 0.2647 0.20 0.10 - -
Mg 0.50 - - 0.0025 - - - 0.30
Cl 0.30 0.39 0.39 0.502 0.30 0.10 - 0.40
P 2.20 0.51 0.51 0.002 0.30 0.10 - -
S 0.90 0.64 0.64 - 0.20 0.30 0.09 0.10
K - 0.51 0.51 0.0171 0.30 - - -
Ca - - - 0.005 - - - -
Density (g cm−3) 1.09 1.04 1.04 1.00 1.039 1.07 1.05 1.03
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COMS Eye Plaque

The COMS eye plaque was a segment of a spherical shell with 15.05-mm outer radius of curvature and a thickness of 0.5 mm, made of gold with a density of 15.8 g/cm3, which is called the “lip.” The lip provides additional radiation shield for normal tissues around and inside the eye. To hold seeds within the plaque, a seed carrier called silastic insert with a density of 1.12 g/cm3 was attached to the concave surface of the gold alloy [11]. In the present study, a fully loaded 14-mm COMS plaque with 13 125I (models IrSeed-125 and IAI-125A) brachytherapy sources have been simulated. Moreover, the coordinates of the 13 seeds in the silastic insert of the plaque have been selected in accordance with the standard location for COMS plaque [11]. Since a tumor-free margin of 2–3 mm should be considered in compliance with the COMS’ recommendation [22], we used a 14-mm diameter COMS plaque for tumor with 10-mm maximal basal dimension. Mass composition of the Modulay gold alloy backing and silicone rubber, silastic, and seed carrier insert is shown in Table 2. The schematic diagram of a 14-mm COMS ophthalmic plaque with 13 seeds, which is simulated by the GATE 8.2, has been shown in Fig. 2a. Moreover, Fig. 2 b shows the position of the 14-mm COMS plaque with 13 125I brachytherapy sources in the voxelized eye phantom.

Table 2.

Mass compositions and density of the Modulay gold alloy backing and silicone rubber [12]

H C O Si Pt Au Ag Cu Pd Density (g cm−3)
Silastic 6.3 24.9 28.9 39.9 0.005 - - - - 1.12
Gold alloy backing - - - - - 77 14 8 1 15.8
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Fig. 2.

Fig. 2

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a Schematic model of a 14-mm COMS plaque with 13 brachytherapy seeds simulated with GATE. b Demonstration of the 14-mm eye plaque located on the outer surface of the eye-voxelized phantom

125I Brachytherapy Source Specifications

Two models of 125I brachytherapy source for 14-mm COMS eye plaque brachytherapy were considered in this study. The IsoAid Advantage (model IAI-125A) 125I brachytherapy source consists of a silver cylindrical marker with 0.25-mm radius and 3.0-mm length [27]. The entire marker surface is uniformly coated with a mixture of silver iodide (AgI), with the thickness equal to 1 μm. This marker is encapsulated within a titanium cylinder tube of 4.5-mm length, 0.8-mm diameter, and 0.05-mm thickness on top and bottom and 0.35-mm radius at both semispherical ends [27, 28]. Geometric diagram of the IsoAid Advantage 125I brachytherapy source is indicated in Fig. 3a.

Fig. 3.

Fig. 3

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Geometric diagram of the two models of 125I brachytherapy sources simulated by GATE 8.2 code a IsoAid Advantage 125I and b IrSeed-125

IrSeed-125 brachytherapy source, which is manufactured by the AEOI (Atomic Energy Organization of Iran), has been shown in Fig. 3b. This source consists of a silver cylindrical marker with 0.25-mm radius and 3.2 mm in length. 125I isotope is uniformly deposited on the marker with the thickness equal to 1 μm. The silver cylindrical marker is encapsulated within a titanium cylinder tube of 4.7-mm length, 0.8-mm diameter, and 0.06-mm thickness on top and bottom and 0.4-mm radius at both semispherical ends. The space between the marker and titanium encapsulated is filled with air [29]. Energy spectrum used for each source is shown in Table 3 [30, 31].

Table 3.

Photon spectrum of 125I, used in this study [30, 31]

Photon energy (keV) Number of photons in each decay
27.202 0.277030
27.472 0.51172
30.944 0.04723
30.995 0.09128
31.704 0.02628
35.4922 0.04619
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Monte Carlo Simulation

In the present study, the MC simulations were divided into two parts: (1) single seed in water medium and (2) eye plaque fully loaded with seeds. At first, IrSeed and IsoAid brachytherapy seeds were defined into the GATE Monte Carlo code (version 8.2). This platform, based on several hundred C++ classes, is designed to meet the specific needs of the simulations of nuclear medicine [32, 33]. The GATE synthesizes the advantages of the GEANT4 Monte Carlo code toolkit well-validated physics models, high-level geometry description, and powerful visualization and 3D rendering tools with original features specific to emission tomography [32] as well as radiation therapy [33].

Iodine-125 (gamma source) was explicitly defined by using a predefined spectrum (as listed in Table 3), as a cylinder with outer radius, thickness, and length of 0.25 mm, 1 μm, and 3.2 mm, respectively. Validation of the brachytherapy sources was carried out according to the TG-43U1 protocol and compared with other studies when available [27, 34–36]. Dosimetry calculations (consist of plaque central-axis depth-dose, percentage dose profile, and dose-volume histogram (DVH) of the tumor) have been performed for a 14-mm COMS eye plaque loaded with 13 125I brachytherapy sources (two models IrSeed and IsoAid). In this way, we developed an eye-voxelized phantom consisting of a medium-sized tumor with an apex height of nearly 5 mm, which is located in the inner surface sclera. The eye-voxelized phantom was designed in MATLAB code (as a 3D matrix), and converted to the Interfile format that is compatible with the GATE code.

The accuracy of the brachytherapy sources used in this study has been validated via calculations of the radial dose function g(r) [24] and compared with the obtained results from other studies. The g(r) was calculated by recording the energy deposited in predefined rings with 0.4-mm radius in the range of 0.1 to 10 cm around the source within a spherical water phantom with 20-cm radius by the GATE simulation code. According to TG-43U1 recommendations, water with a mass density of 0.998 g/cm3 was considered dosimetry media. Simulations were performed with emstandard_opt3 physics list and 5 × 109 particles and were followed to obtain the least statistical uncertainty (< 1%). To calculate the radial dose function, rings with 0.4-mm thicknesses were located at different distances from the source center [35].

Results

Single Source

Values of the radial dose function were calculated by the GATE 8.2 code for distances from 0.1 to 7 cm and 0.5 to 10 cm from the source center for IrSeed-125 and IsoAid Advantage, respectively. The comparison between the theoretical and experimental radial dose function for these sources is shown in Fig. 4. According to Fig. 4a, there is a good agreement between IrSeed-125 simulation results using the GATE 8.2 code and reporting measurements [29] and simulation [35] results with MCNP code. The mean differences between our results with those of experiments and MCNP simulation were about 4.4% and 5.0%, respectively. Figure 4 b demonstrates excellent agreement (within ± 7%) between the presently calculated radial dose function of 125I IsoAid brachytherapy source and the reported data by Meigooni et al. [27], Aryal et al. [34], and Solberg et al. [36].

Fig. 4.

Fig. 4

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Comparison of the radial dose function obtained from GATE 8.2 code and other experimental and calculated results for a IrSeed-125 source and b IsoAid Advantage 125I sources

As seen in these diagrams, there is a good agreement between the GATE 8.2 results and those of other studies.

Eye Dosimetry Calculations

In this work, the COMS plaque containing IsoAid (IrSeed) brachytherapy source was positioned into the coupled model of the ocular area, and simulations on the GATE code were carried on. The plaque was placed on the outer surface of sclera behind the tumor base.

Because of the COMS dose prescription criteria imply that a maximum dose of 85 Gy should be delivered to the tumor apex [17], calculated doses were normalized to the 85 Gy at the apex of the eye tumor. Table 4 demonstrates the normalized average absorbed doses in the various eye structures for each source model. The maximum received dose to the tumor in this work has an excellent agreement with other studies [11, 17]. According to these results, the eye components that received higher doses are tumor, sclera, vitreous, and retina, respectively. Although the average dose results in the eye components represent that doses to different structures of the eye due to IsoAid Advantage are more than the IrSeed-125 source, the ratios of absorbed dose of the tumor to the sclera, vitreous, and retina are similar to each other. The ratios of mean absorbed dose of the tumor to the sclera, vitreous, and retina for IrSeed (IsoAid) source are 3.7 (3.7), 6.2 (6.1), and 6.3 (6.3), respectively, which represents the dose saving to healthy tissues.

Table 4.

Average doses in the eye components in Gray due to the IrSeed-125 and IsoAid Advantage 125I seeds

Eye structure Average dose (Gy)
IrSeed-125 IsoAid Advantage
Sclera 44.277 46.548
Choroid 25.180 26.437
Retina 26.044 27.365
Vitreous 26.648 27.979
Lens 14.198 14.947
Cornea 9.146 9.626
Anterior chamber 10.848 11.389
Ciliary body 18.993 19.987
Optic nerve 4.952 5.202
Tumor 164.779 173.321
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All results are normalized to deliver a dose of 85 Gy to the tumor apex

On the other hand, calculated dose in the eye tumor, which is about 173.321 Gy for IsoAid Advantage 125I, is in good agreement with the corresponding result calculated by Ebrahimi Khankook et al. [17], which is about 186 Gy by using Yoriyaz mathematical models (absolute difference about 6.8%). It should be noted that in the Ebrahimi Khankook et al. [17] study, results are presented for 12-mm COMS plaque with eight brachytherapy seeds. To calculate dose deposited in the different components of the eye phantom, the resulting dose distribution in the phantom was stored into a 3D image (.mhd file format) with a voxel size of 0.1 × 0.1 × 0.1 mm3 by the GATE simulation code. Then, the 3D image of dose distribution was converted into a 3D matrix (dose matrix) using the MATLAB code. Finally, the dose deposition in each internal structures of the eye phantom was calculated by averaging the values of the voxels within each region.

Depth dose curves along the central axis of the COMS plaque are shown in Fig. 5. 5 × 109 histories have been followed for this case, and relative statistical uncertainty for dose in each voxel was less than 3%. A 0.1-mm range cutoff in the seeds and eye phantom was used for photons and electrons and no other variance reduction techniques were used.

Fig. 5.

Fig. 5

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The plaque central axis depth-dose curves due to IrSeed-125 and IsoAid Advantage 125I seeds

Because of the similarity between the geometry of the IsoAid and IrSeed sources, it is clear that the depth dose curve due to the IrSeed source is approximately similar to that of the IsoAid.

Figure 6 demonstrates the lateral profile dose distributions perpendicular to the symmetry axis of eye phantom at the largest lateral dimension of the tumor, which is calculated in the 0.1-mm3 voxels with the GATE code. In addition to the doses along the central-axis and lateral profile dose distributions, dose-volume histogram (DVH) of the tumor is important in assessing the quality of brachytherapy.

Fig. 6.

Fig. 6

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Lateral dose distributions calculated using GATE for the plaque with IrSeed and IsoAid brachytherapy sources

Figure 7 shows the comparisons of tumor DVHs due to each source model at the same prescription dose of the 85 Gy to the tumor apex. The curves indicate that the DVHs of the tumor for both types of sources are very similar; there is a minor difference between the two models of sources. The maximum percentage differences between the DVH curve of IsoAid and IrSeed seeds was about 8%.

Fig. 7.

Fig. 7

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DVH of the tumor for the plaque with IrSeed and IsoAid brachytherapy sources

Figure 8 presents the central cross section of voxelized eye model, which is fused by related absorbed dose distribution, and is plotted altogether for a 14-mm COMS plaque loaded with IsoAid (8a) and IrSeed (8b). As shown in this figure, the maximum dose is distributed within the base of the tumor, and with increasing the distance from the center of the plaque, the dose distribution decreases rapidly, that is, the main advantage of brachytherapy techniques for treatment of intraocular tumors.

Fig. 8.

Fig. 8

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Central cross section of voxelized eye model, which is fused by related absorbed dose distribution for a IsoAid and b IrSeed-125 sources

Conclusions

We simulated two Iodine-125 brachytherapy source models, which are low-energy photon emitter with maximum energy of 35 keV, by using the GATE Monte Carlo simulation code for eye melanoma treatment. At first, the radial dose function of the IrSeed-125 and IsoAid Advantage brachytherapy source models was obtained using the GATE code. The results were compared with previous studies. The obtained results, which are presented in Fig. 4, show good consistency with the experimental and calculated data. Then, with developing a voxelized eye phantom, we evaluate the dose distribution for the 14-mm COMS eye plaque loaded with 13 IrSeed-125 sources in comparison with that loaded with IsoAid sources, which have a smaller size, by the GATE Monte Carlo code. The calculated absorbed dose results in the eye components for the IrSeed-125 and IsoAid seeds, which were normalized to deliver dose of the 85 Gy at the tumor apex, show that although different eye structures receive more dose by using IsoAid than IrSeed-125 seeds, the ratio of absorbed dose of the tumor to the different substructures of the eye, such as the sclera, vitreous, and retina are similar for two different source models. It is noted that the tumor size and position of it may differ from patient to patient; thus, the treatment time can be changed to deliver the prescribed dose.

On the other hand, the results of plaque central-axis depth-dose, lateral dose distributions, and DVH of the tumor for two different models obtained using the GATE Monte Carlo platform are very similar to each other. Our simulation results show that a new design of 125I source can be used in ophthalmic plaques to treat ophthalmic tumors. A practical dosimetric investigation (such as by using radiochromic films) should be used before clinical trials on humans for IrSeed-125 eye plaques.

Compliance with Ethical Standards

Conflict of Interest

Payvand Taherparvar and Zeinab Fardi declare that they have no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed Consent

The institutional review board of our institute approved this retrospective study, and the requirement to obtain informed consent was waived

Footnotes

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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