Ex) Article Title, Author, Keywords
Ex) Article Title, Author, Keywords
Progress in Medical Physics 2022; 33(4): 114-120
Published online December 31, 2022
https://doi.org/10.14316/pmp.2022.33.4.114
Copyright © Korean Society of Medical Physics.
Correspondence to:Sang Hee Ahn
(rodlming84@gmail.com)
Tel: 82-2-3410-1864
Fax: 82-2-3410-2619
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Purpose: Particle beam therapy is advantageous over photon therapy. However, adequately delivering therapeutic doses to tumors near critical organs is difficult. Nanoparticle-aided radiation therapy can be used to alleviate this problem, wherein nanoparticles can passively accumulate at higher concentrations in the tumor tissue compared to the surrounding normal tissue. In this study, we investigate the dose enhancement effect due to gold nanoparticle (GNP) when Carbon-12, He-4, and proton beams are irradiated on GNP.
Methods: First, monoenergetic Carbon-12 and He-4 ion beams of energy of 283.33 MeV/u and 150 MeV/u, respectively, and a proton beam of energy of 150 MeV were irradiated on a water phantom of dimensions 30 cm×30 cm×30 cm. Subsequently, the secondary-particle information generated near the Bragg peak was recorded in a phase-space (phsp) file. Second, the obtained phsp file was scaled down to a nanometer scale to irradiate GNP of diameter 50 nm located at the center of a 4 µm×4 µm×4 µm water phantom. The dose enhancement ratio (DER) was calculated in intervals of 1 nm from the GNP surface.
Results: The DER of GNP computed at 1 nm from the GNP surface was 4.70, 4.86, and 4.89 for Carbon-12, He-4, and proton beams, respectively; the DER decreased rapidly with increasing distance from the GNP surface.
Conclusions: The results indicated that GNP can be used as radiosensitizers in particle beam therapy. Furthermore, the dose enhancement effect of the GNP absorbed by tumor cells can aid in delivering higher therapeutic doses.
KeywordsGold nanoparticle, Dose enhancement, Monte Carlo simulation, Radiosensitizer, Particle beam therapy
Radiation therapy aims to selectively deliver a higher radiation dose to a tumor while minimizing the toxicity in the surrounding normal tissue. Particle beam therapy is advantageous over photon therapy because it enables highly conventional radiation delivery while minimizing the dose to normal tissue [1,2]. However, adequately delivering therapeutic doses to tumors close to critical organs is difficult. To overcome these limitations, nanoparticle-aided radiation therapy (NART) can be used [3]. Nanoparticles possess the ability to passively accumulate in higher concentrations in tumor tissue than in the surrounding normal tissue when injected into the bloodstream because of the enhanced permeation and retention effect [4]. Gold (Z=79) has been suggested to locally sensitize tumors in NART. Recently, radiation therapy using charged particles, including proton beam therapy, has been used [5]. This study investigates the physical dose enhancement of gold nanoparticle (GNP) when scanned beams of Carbon-12, He-4, and proton are irradiated on GNP, through a Monte Carlo simulation.
TOPAS version 3.1 patch 03 [6] was used for dose calculation via Monte Carlo simulation. Scanned monoenergetic Carbon-12 and He-4 particle beams of energy of 283.33 MeV/u and 150 MeV/u, respectively, and a proton beam of energy of 150 MeV were incident on a water phantom based on the same Bragg peak position (Fig. 1). To shorten the computation time, three-step simulations were conducted (Fig. 2). The first step was a macroscopic simulation of scanned beams of Carbon-12, He-4, and proton [7] of diameter 1 cm irradiating a water phantom with the dimensions of 30 cm×30 cm×30 cm [8]. Information regarding the Bragg peak position of all the energy particles was recorded in a phsp file (Fig. 2). In the second step, the primary- and secondary-particle information contained in the obtained phsp file was used to scale down the beam diameter to 50 nm, which was irradiated on GNP located at the center of a water phantom of dimensions 4 μm×4 μm×4 μm. Gold and water were assumed to be spherical. All the secondary particles emitted by various GNP at the water phantom surface were recorded in the spherical phsp files. In the third step, a 1-nm-wide detector comprising concentric shells was built and placed at a distance of 50 nm from the GNP surface to measure the dose. The dose enhancement ratio (DER) was computed as the ratio of the radiation dose with GNP to the dose with the GNP replaced by the same amount of water. This method is not realistic, but a nano-sized beam generates sufficient interaction between the primary protons and the GNP. Thus, the DER is defined by using the following formula:
The step size for all particles was set to 1 nm in all simulations; furthermore, two physics models were used in the simulations. DER-calculation results indicate GNP uptake inside the tumor, and dose enhancement in the closest area is important. Therefore, in the current simulation conditions, the deposited dose of 1 nm, which is the shortest distance from the nanoparticle surface, was normalized based on water. The Geant4-Livermore physics model [9], which allows for the tracking of electrons with energy down to 10 eV, was used for the simulation inside the GNP. The Geant4-DNA physics model, which allows for the tracking of electrons with energy down to 7.4 eV in water, was used for the simulation outside the GNP [10]. The Geant4-DNA physics model has been proven to be an accurate low-energy physics model for performing nano-dosimetry of the DNA damage caused by electrons and heavy ions [11]; however, it is valid only for liquid water. In the simulation, the histories of 1×108 protons were used. The dose calculations for the irradiation of a nano-sized proton beam on one material took approximately 24 hours.
Table 1 presents the yield ratios of the secondary particles produced by the incident primary particles’ interaction with the water phantom at the Bragg peak position. For Carbon-12 and He-4, the neutrons exhibited the highest production rate. Proton exhibited the highest production of secondary protons. In NART, the rate of generation of electrons transferring energy directly to the tumor tissue is important. The proportion of electrons generated on the GNP surface was the highest at 7.72E−01 for Carbon-12, followed by those of He-4 (1.61E−01) and proton (3.74E−02) (Table 2). When Carbon-12, He-4, and protons irradiated the GNP, the production rate of gamma was 3.10E−04, 4.52E−05, and 9.20E−06, respectively. According to Egorov and Egorvov [12], the higher the atomic number, the higher the cross-section of gamma yield. Particularly, if the yield ratio in the K shell exceeds 1, the atomic number must satisfy 20 or more. However, for water, the effective atomic number is about 7.4, which is lower than that of gold (Z=79). Therefore, gamma particles were not detected in the simulation of this study (Table 3). For radial DER owing to the secondary particles, no significant difference was observed based on the incident primary particles (Fig. 3). Note that an absence of difference in the physical dose enhancement does not necessarily indicate that the biochemical effects are similar. Recently, Rudek et al. [13] performed simulations to consider the effects of water radiolysis on GNP in their in silico study. Similarly, our study requires further investigation considering the effects of radiolysis. Fig. 4 shows the dose imparted by the secondary particles generated per incident primary particle at shell-type detectors. It is observed that Carbon-12 features the highest ionization ratio, followed by He-4 and protons. Fig. 4 further shows that the ionization ratio decreases as the distance from the GNP surface increases. In particular, the reduction ratio of ionization is maintained according to the distance to water and GNP according to each of the incident Carbon-12, He-4, and proton particles. This corroborates the result that the radial DER does not cause any significant difference in physical dose enhancement. This result indicates that GNP can be used as radiosensitizers for particle beam therapy [14].
Table 1 The proportion of secondary particles generated by the interaction of Carbon-12, He-4, and proton beams with water phantom at the Bragg peak position
Secondary particle | Yield ratio (number of scoring secondary particles/number of incident primary particles) | ||
---|---|---|---|
Carbon-12 | He-4 | Proton | |
Proton | 7.50E+0 | 1.01E+0 | 5.82E+0 |
Gamma | 1.65E+01 | 5.36E+0 | 1.15E+0 |
Positron | 1.67E–02 | 6.88E–03 | 1.72E–03 |
Electron | 3.26E+0 | 1.96E–01 | 2.78E–02 |
Neutron | 1.97E+01 | 7.63E+0 | 1.00E+0 |
Deuteron | 1.64E+0 | 9.87E–01 | 1.75E–04 |
Alpha | 3.66E+0 | 5.77E+0 | 3.20E–05 |
Anti-neutrino electron | 1.33E–05 | 7.00E–06 | 3.00E–06 |
Tritron | 4.89E–01 | 2.65E–01 | 2.00E–06 |
Carbon-12 | 2.86E+0 | 3.80E–05 | 5.00E–06 |
Nitrogen-15 | 1.31E–04 | 1.10E–05 | 1.00E–06 |
Oxygen-15 | 3.00E–05 | 5.00E–06 | 1.00E–06 |
Oxygen-16 | 2.42E–04 | 6.60E–05 | 2.70E–05 |
Helium-3 | 4.53E–01 | 1.16E–02 | 2.00E–06 |
Fluorine-17 | 3.80E–05 | 1.20E–05 | 1.00E–06 |
Table 2 The yield of secondary electrons from different incident primary particles
Incident primary particle | Yield ratio (number of generated secondary particles/number of incident primary particles) | |
---|---|---|
Gold | Water | |
Carbon-12 | 7.72E–01 | 1.16E–01 |
He-4 | 1.61E–01 | 2.38E–02 |
Proton | 3.74E–02 | 5.48E–03 |
Table 3 The yield of secondary gamma from different incident primary particles
Incident primary particle | Yield ratio (number of generated secondary particles/number of incident primary particles) | |
---|---|---|
Gold | Water | |
Carbon-12 | 3.10E–04 | 7.00E–07 |
He-4 | 4.52E–05 | - |
Proton | 9.20E–06 | - |
This study investigated the dose enhancement effect of GNP when Carbon-12, He-4, and proton beams are irradiated on GNP, through a Monte Carlo simulation because gold (Z=79) has been suggested to locally sensitize tumors in NART. Therefore, scanned monoenergetic Carbon-12 and He-4 ion beams of energies of 283.33 MeV/u and 150 MeV/u, respectively, and a proton beam of energy of 150 MeV was made incident on a water phantom of dimensions 30 cm×30 cm×30 cm. Subsequently, the information regarding the particles’ Bragg peak position was recorded in a phsp file. Further, the phsp file was used to scale down the beam diameter to 50 nm, which was irradiated on a water phantom of dimensions 4 μm×4 μm×4 μm containing GNP. To measure the dose, a 1 nm-wide detector comprising concentric shells was fabricated and placed at a distance of 50 nm from the GNP surface. The DER was calculated in intervals of 1 nm from the GNP surface. The results indicated that GNP can be used as radiosensitizers for particle beam therapy. Further, DER decreased with increasing distance from the GNP surface, but it did not differ significantly for Carbon-12, He-4, and the proton beams. (Fig..3)
In summary, when GNP is combined as a radiosensitizer in a particle beam, the dose enhancement effect can effectively deliver a dose to tumor cells. There is no difference in the effect of dose enhancement based on particle beams. However, it is expected that the treatment effect in combination with particle beam therapy and GNP will increase upon local tumor sensitization by up to approximately five times the dose enhancement role near the GNP inside the tumor.
This study was supported by the Ministry of Science and ICT (2022R1F1A1070271).
The author has nothing to disclose.
All relevant data are within the paper and its Supporting Information files.
Progress in Medical Physics 2022; 33(4): 114-120
Published online December 31, 2022 https://doi.org/10.14316/pmp.2022.33.4.114
Copyright © Korean Society of Medical Physics.
Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Correspondence to:Sang Hee Ahn
(rodlming84@gmail.com)
Tel: 82-2-3410-1864
Fax: 82-2-3410-2619
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Purpose: Particle beam therapy is advantageous over photon therapy. However, adequately delivering therapeutic doses to tumors near critical organs is difficult. Nanoparticle-aided radiation therapy can be used to alleviate this problem, wherein nanoparticles can passively accumulate at higher concentrations in the tumor tissue compared to the surrounding normal tissue. In this study, we investigate the dose enhancement effect due to gold nanoparticle (GNP) when Carbon-12, He-4, and proton beams are irradiated on GNP.
Methods: First, monoenergetic Carbon-12 and He-4 ion beams of energy of 283.33 MeV/u and 150 MeV/u, respectively, and a proton beam of energy of 150 MeV were irradiated on a water phantom of dimensions 30 cm×30 cm×30 cm. Subsequently, the secondary-particle information generated near the Bragg peak was recorded in a phase-space (phsp) file. Second, the obtained phsp file was scaled down to a nanometer scale to irradiate GNP of diameter 50 nm located at the center of a 4 µm×4 µm×4 µm water phantom. The dose enhancement ratio (DER) was calculated in intervals of 1 nm from the GNP surface.
Results: The DER of GNP computed at 1 nm from the GNP surface was 4.70, 4.86, and 4.89 for Carbon-12, He-4, and proton beams, respectively; the DER decreased rapidly with increasing distance from the GNP surface.
Conclusions: The results indicated that GNP can be used as radiosensitizers in particle beam therapy. Furthermore, the dose enhancement effect of the GNP absorbed by tumor cells can aid in delivering higher therapeutic doses.
Keywords: Gold nanoparticle, Dose enhancement, Monte Carlo simulation, Radiosensitizer, Particle beam therapy
Radiation therapy aims to selectively deliver a higher radiation dose to a tumor while minimizing the toxicity in the surrounding normal tissue. Particle beam therapy is advantageous over photon therapy because it enables highly conventional radiation delivery while minimizing the dose to normal tissue [1,2]. However, adequately delivering therapeutic doses to tumors close to critical organs is difficult. To overcome these limitations, nanoparticle-aided radiation therapy (NART) can be used [3]. Nanoparticles possess the ability to passively accumulate in higher concentrations in tumor tissue than in the surrounding normal tissue when injected into the bloodstream because of the enhanced permeation and retention effect [4]. Gold (Z=79) has been suggested to locally sensitize tumors in NART. Recently, radiation therapy using charged particles, including proton beam therapy, has been used [5]. This study investigates the physical dose enhancement of gold nanoparticle (GNP) when scanned beams of Carbon-12, He-4, and proton are irradiated on GNP, through a Monte Carlo simulation.
TOPAS version 3.1 patch 03 [6] was used for dose calculation via Monte Carlo simulation. Scanned monoenergetic Carbon-12 and He-4 particle beams of energy of 283.33 MeV/u and 150 MeV/u, respectively, and a proton beam of energy of 150 MeV were incident on a water phantom based on the same Bragg peak position (Fig. 1). To shorten the computation time, three-step simulations were conducted (Fig. 2). The first step was a macroscopic simulation of scanned beams of Carbon-12, He-4, and proton [7] of diameter 1 cm irradiating a water phantom with the dimensions of 30 cm×30 cm×30 cm [8]. Information regarding the Bragg peak position of all the energy particles was recorded in a phsp file (Fig. 2). In the second step, the primary- and secondary-particle information contained in the obtained phsp file was used to scale down the beam diameter to 50 nm, which was irradiated on GNP located at the center of a water phantom of dimensions 4 μm×4 μm×4 μm. Gold and water were assumed to be spherical. All the secondary particles emitted by various GNP at the water phantom surface were recorded in the spherical phsp files. In the third step, a 1-nm-wide detector comprising concentric shells was built and placed at a distance of 50 nm from the GNP surface to measure the dose. The dose enhancement ratio (DER) was computed as the ratio of the radiation dose with GNP to the dose with the GNP replaced by the same amount of water. This method is not realistic, but a nano-sized beam generates sufficient interaction between the primary protons and the GNP. Thus, the DER is defined by using the following formula:
The step size for all particles was set to 1 nm in all simulations; furthermore, two physics models were used in the simulations. DER-calculation results indicate GNP uptake inside the tumor, and dose enhancement in the closest area is important. Therefore, in the current simulation conditions, the deposited dose of 1 nm, which is the shortest distance from the nanoparticle surface, was normalized based on water. The Geant4-Livermore physics model [9], which allows for the tracking of electrons with energy down to 10 eV, was used for the simulation inside the GNP. The Geant4-DNA physics model, which allows for the tracking of electrons with energy down to 7.4 eV in water, was used for the simulation outside the GNP [10]. The Geant4-DNA physics model has been proven to be an accurate low-energy physics model for performing nano-dosimetry of the DNA damage caused by electrons and heavy ions [11]; however, it is valid only for liquid water. In the simulation, the histories of 1×108 protons were used. The dose calculations for the irradiation of a nano-sized proton beam on one material took approximately 24 hours.
Table 1 presents the yield ratios of the secondary particles produced by the incident primary particles’ interaction with the water phantom at the Bragg peak position. For Carbon-12 and He-4, the neutrons exhibited the highest production rate. Proton exhibited the highest production of secondary protons. In NART, the rate of generation of electrons transferring energy directly to the tumor tissue is important. The proportion of electrons generated on the GNP surface was the highest at 7.72E−01 for Carbon-12, followed by those of He-4 (1.61E−01) and proton (3.74E−02) (Table 2). When Carbon-12, He-4, and protons irradiated the GNP, the production rate of gamma was 3.10E−04, 4.52E−05, and 9.20E−06, respectively. According to Egorov and Egorvov [12], the higher the atomic number, the higher the cross-section of gamma yield. Particularly, if the yield ratio in the K shell exceeds 1, the atomic number must satisfy 20 or more. However, for water, the effective atomic number is about 7.4, which is lower than that of gold (Z=79). Therefore, gamma particles were not detected in the simulation of this study (Table 3). For radial DER owing to the secondary particles, no significant difference was observed based on the incident primary particles (Fig. 3). Note that an absence of difference in the physical dose enhancement does not necessarily indicate that the biochemical effects are similar. Recently, Rudek et al. [13] performed simulations to consider the effects of water radiolysis on GNP in their in silico study. Similarly, our study requires further investigation considering the effects of radiolysis. Fig. 4 shows the dose imparted by the secondary particles generated per incident primary particle at shell-type detectors. It is observed that Carbon-12 features the highest ionization ratio, followed by He-4 and protons. Fig. 4 further shows that the ionization ratio decreases as the distance from the GNP surface increases. In particular, the reduction ratio of ionization is maintained according to the distance to water and GNP according to each of the incident Carbon-12, He-4, and proton particles. This corroborates the result that the radial DER does not cause any significant difference in physical dose enhancement. This result indicates that GNP can be used as radiosensitizers for particle beam therapy [14].
Table 1 . The proportion of secondary particles generated by the interaction of Carbon-12, He-4, and proton beams with water phantom at the Bragg peak position.
Secondary particle | Yield ratio (number of scoring secondary particles/number of incident primary particles) | ||
---|---|---|---|
Carbon-12 | He-4 | Proton | |
Proton | 7.50E+0 | 1.01E+0 | 5.82E+0 |
Gamma | 1.65E+01 | 5.36E+0 | 1.15E+0 |
Positron | 1.67E–02 | 6.88E–03 | 1.72E–03 |
Electron | 3.26E+0 | 1.96E–01 | 2.78E–02 |
Neutron | 1.97E+01 | 7.63E+0 | 1.00E+0 |
Deuteron | 1.64E+0 | 9.87E–01 | 1.75E–04 |
Alpha | 3.66E+0 | 5.77E+0 | 3.20E–05 |
Anti-neutrino electron | 1.33E–05 | 7.00E–06 | 3.00E–06 |
Tritron | 4.89E–01 | 2.65E–01 | 2.00E–06 |
Carbon-12 | 2.86E+0 | 3.80E–05 | 5.00E–06 |
Nitrogen-15 | 1.31E–04 | 1.10E–05 | 1.00E–06 |
Oxygen-15 | 3.00E–05 | 5.00E–06 | 1.00E–06 |
Oxygen-16 | 2.42E–04 | 6.60E–05 | 2.70E–05 |
Helium-3 | 4.53E–01 | 1.16E–02 | 2.00E–06 |
Fluorine-17 | 3.80E–05 | 1.20E–05 | 1.00E–06 |
Table 2 . The yield of secondary electrons from different incident primary particles.
Incident primary particle | Yield ratio (number of generated secondary particles/number of incident primary particles) | |
---|---|---|
Gold | Water | |
Carbon-12 | 7.72E–01 | 1.16E–01 |
He-4 | 1.61E–01 | 2.38E–02 |
Proton | 3.74E–02 | 5.48E–03 |
Table 3 . The yield of secondary gamma from different incident primary particles.
Incident primary particle | Yield ratio (number of generated secondary particles/number of incident primary particles) | |
---|---|---|
Gold | Water | |
Carbon-12 | 3.10E–04 | 7.00E–07 |
He-4 | 4.52E–05 | - |
Proton | 9.20E–06 | - |
This study investigated the dose enhancement effect of GNP when Carbon-12, He-4, and proton beams are irradiated on GNP, through a Monte Carlo simulation because gold (Z=79) has been suggested to locally sensitize tumors in NART. Therefore, scanned monoenergetic Carbon-12 and He-4 ion beams of energies of 283.33 MeV/u and 150 MeV/u, respectively, and a proton beam of energy of 150 MeV was made incident on a water phantom of dimensions 30 cm×30 cm×30 cm. Subsequently, the information regarding the particles’ Bragg peak position was recorded in a phsp file. Further, the phsp file was used to scale down the beam diameter to 50 nm, which was irradiated on a water phantom of dimensions 4 μm×4 μm×4 μm containing GNP. To measure the dose, a 1 nm-wide detector comprising concentric shells was fabricated and placed at a distance of 50 nm from the GNP surface. The DER was calculated in intervals of 1 nm from the GNP surface. The results indicated that GNP can be used as radiosensitizers for particle beam therapy. Further, DER decreased with increasing distance from the GNP surface, but it did not differ significantly for Carbon-12, He-4, and the proton beams. (Fig..3)
In summary, when GNP is combined as a radiosensitizer in a particle beam, the dose enhancement effect can effectively deliver a dose to tumor cells. There is no difference in the effect of dose enhancement based on particle beams. However, it is expected that the treatment effect in combination with particle beam therapy and GNP will increase upon local tumor sensitization by up to approximately five times the dose enhancement role near the GNP inside the tumor.
This study was supported by the Ministry of Science and ICT (2022R1F1A1070271).
The author has nothing to disclose.
All relevant data are within the paper and its Supporting Information files.
Table 1 The proportion of secondary particles generated by the interaction of Carbon-12, He-4, and proton beams with water phantom at the Bragg peak position
Secondary particle | Yield ratio (number of scoring secondary particles/number of incident primary particles) | ||
---|---|---|---|
Carbon-12 | He-4 | Proton | |
Proton | 7.50E+0 | 1.01E+0 | 5.82E+0 |
Gamma | 1.65E+01 | 5.36E+0 | 1.15E+0 |
Positron | 1.67E–02 | 6.88E–03 | 1.72E–03 |
Electron | 3.26E+0 | 1.96E–01 | 2.78E–02 |
Neutron | 1.97E+01 | 7.63E+0 | 1.00E+0 |
Deuteron | 1.64E+0 | 9.87E–01 | 1.75E–04 |
Alpha | 3.66E+0 | 5.77E+0 | 3.20E–05 |
Anti-neutrino electron | 1.33E–05 | 7.00E–06 | 3.00E–06 |
Tritron | 4.89E–01 | 2.65E–01 | 2.00E–06 |
Carbon-12 | 2.86E+0 | 3.80E–05 | 5.00E–06 |
Nitrogen-15 | 1.31E–04 | 1.10E–05 | 1.00E–06 |
Oxygen-15 | 3.00E–05 | 5.00E–06 | 1.00E–06 |
Oxygen-16 | 2.42E–04 | 6.60E–05 | 2.70E–05 |
Helium-3 | 4.53E–01 | 1.16E–02 | 2.00E–06 |
Fluorine-17 | 3.80E–05 | 1.20E–05 | 1.00E–06 |
Table 2 The yield of secondary electrons from different incident primary particles
Incident primary particle | Yield ratio (number of generated secondary particles/number of incident primary particles) | |
---|---|---|
Gold | Water | |
Carbon-12 | 7.72E–01 | 1.16E–01 |
He-4 | 1.61E–01 | 2.38E–02 |
Proton | 3.74E–02 | 5.48E–03 |
Table 3 The yield of secondary gamma from different incident primary particles
Incident primary particle | Yield ratio (number of generated secondary particles/number of incident primary particles) | |
---|---|---|
Gold | Water | |
Carbon-12 | 3.10E–04 | 7.00E–07 |
He-4 | 4.52E–05 | - |
Proton | 9.20E–06 | - |
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