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Title: SU-E-T-30: A Factor for Converting Dose to a Gold Nanoparticle Mixture to a Biologically-Relevant Dose

Abstract

Purpose: Monte Carlo studies of gold nanoparticle (GNP) dose enhancement on macroscopic scales in radiotherapy have modeled GNPs in tissue as a homogeneous mixture of gold and tissue. Using an explicit model of GNPs randomly positioned in a small volume (1 µm{sup 3}) of tissue, this study aims to quantify the dose to the biologically relevant component of a goldtissue mixture, enabling a conversion from macroscopically-scored dose. Methods: Using the PENELOPE Monte Carlo code with the penEasy package, we modeled a 1 µm{sup 3} volume containing either a tissue-gold mixture or GNPs suspended in ICRU 4-component tissue at various gold concentrations (0, 5, 10, and 15 mg Au/g tissue) and GNP diameters (20, 30, 40, 50 nm). The volume was irradiated with monoenergetic photon and electron beams, ranging from 110 eV to 6 MeV. Interaction forcing was utilized to increase simulation efficiency. Energy deposition was scored in the tissue for each case and was converted to dose. For each scenario, we calculated a conversion factor, the ratio of dose-to-tissue to dose-to-mixture as a function of energy. Results: The conversion factor was plotted as a function of energy for both photons and electrons. For electrons, the conversion factor was relatively unaffectedmore » by any of the parameters, including energy, ranging between 0.98–1.02. For photons, the factor was very energy dependent, with a range of 0.49–1.02. The factor was lowest for 10–100 keV photons. The conversion factor generally decreased with increasing GNP concentration and increasing GNP size. Conclusion: With a large variation in the conversion factor with incident energy, dose deposition is dependent on the spectrum incident on a volume. By scoring the energy spectrum in a given volume, one can provide a scenario-specific conversion factor, allowing fast, detailed Monte Carlo simulations without the need for explicit GNP-definition.« less

Authors:
 [1];  [2];  [1];  [2]
  1. University of Calgary, Calgary, AB (Canada)
  2. (Canada)
Publication Date:
OSTI Identifier:
22545164
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 42; Journal Issue: 6; Other Information: (c) 2015 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; ANIMAL TISSUES; COMPUTERIZED SIMULATION; CONCENTRATION RATIO; ELECTRON BEAMS; ENERGY ABSORPTION; ENERGY DEPENDENCE; ENERGY LOSSES; ENERGY SPECTRA; HOMOGENEOUS MIXTURES; ICRU; IRRADIATION; MONTE CARLO METHOD; NANOPARTICLES; RADIATION DOSES; RADIOTHERAPY

Citation Formats

Koger, B, Tom Baker Cancer Centre, Calgary, AB, Kirkby, C, and Jack Ady Cancer Centre, Lethbridge, AB. SU-E-T-30: A Factor for Converting Dose to a Gold Nanoparticle Mixture to a Biologically-Relevant Dose. United States: N. p., 2015. Web. doi:10.1118/1.4924391.
Koger, B, Tom Baker Cancer Centre, Calgary, AB, Kirkby, C, & Jack Ady Cancer Centre, Lethbridge, AB. SU-E-T-30: A Factor for Converting Dose to a Gold Nanoparticle Mixture to a Biologically-Relevant Dose. United States. doi:10.1118/1.4924391.
Koger, B, Tom Baker Cancer Centre, Calgary, AB, Kirkby, C, and Jack Ady Cancer Centre, Lethbridge, AB. Mon . "SU-E-T-30: A Factor for Converting Dose to a Gold Nanoparticle Mixture to a Biologically-Relevant Dose". United States. doi:10.1118/1.4924391.
@article{osti_22545164,
title = {SU-E-T-30: A Factor for Converting Dose to a Gold Nanoparticle Mixture to a Biologically-Relevant Dose},
author = {Koger, B and Tom Baker Cancer Centre, Calgary, AB and Kirkby, C and Jack Ady Cancer Centre, Lethbridge, AB},
abstractNote = {Purpose: Monte Carlo studies of gold nanoparticle (GNP) dose enhancement on macroscopic scales in radiotherapy have modeled GNPs in tissue as a homogeneous mixture of gold and tissue. Using an explicit model of GNPs randomly positioned in a small volume (1 µm{sup 3}) of tissue, this study aims to quantify the dose to the biologically relevant component of a goldtissue mixture, enabling a conversion from macroscopically-scored dose. Methods: Using the PENELOPE Monte Carlo code with the penEasy package, we modeled a 1 µm{sup 3} volume containing either a tissue-gold mixture or GNPs suspended in ICRU 4-component tissue at various gold concentrations (0, 5, 10, and 15 mg Au/g tissue) and GNP diameters (20, 30, 40, 50 nm). The volume was irradiated with monoenergetic photon and electron beams, ranging from 110 eV to 6 MeV. Interaction forcing was utilized to increase simulation efficiency. Energy deposition was scored in the tissue for each case and was converted to dose. For each scenario, we calculated a conversion factor, the ratio of dose-to-tissue to dose-to-mixture as a function of energy. Results: The conversion factor was plotted as a function of energy for both photons and electrons. For electrons, the conversion factor was relatively unaffected by any of the parameters, including energy, ranging between 0.98–1.02. For photons, the factor was very energy dependent, with a range of 0.49–1.02. The factor was lowest for 10–100 keV photons. The conversion factor generally decreased with increasing GNP concentration and increasing GNP size. Conclusion: With a large variation in the conversion factor with incident energy, dose deposition is dependent on the spectrum incident on a volume. By scoring the energy spectrum in a given volume, one can provide a scenario-specific conversion factor, allowing fast, detailed Monte Carlo simulations without the need for explicit GNP-definition.},
doi = {10.1118/1.4924391},
journal = {Medical Physics},
number = 6,
volume = 42,
place = {United States},
year = {Mon Jun 15 00:00:00 EDT 2015},
month = {Mon Jun 15 00:00:00 EDT 2015}
}
  • Purpose: There have been several reports of enhanced cell-killing and tumor regression when tumor cells and mouse tumors were loaded with gold nanoparticles (GNPs) prior to proton irradiation. While particle-induced xray emission (PIXE), Auger electrons, secondary electrons, free radicals, and biological effects have been suggested as potential mechanisms responsible for the observed GNP-mediated dose enhancement/radiosensitization, there is a lack of quantitative analysis regarding the contribution from each mechanism. Here, we report our experimental effort to quantify some of these effects. Methods: 5-cm-long cylindrical plastic vials were filled with 1.8 mL of either water or water mixed with cylindrical GNPs atmore » the same gold concentration (0.3 mg Au/g) as used in previous animal studies. A piece of EBT2 radiochromic film (30-µm active-layer sandwiched between 80/175-µm outer-layers) was inserted along the long axis of each vial and used to measure dose enhancement due to PIXE from GNPs. Vials were placed at center-of-modulation (COM) and 3-cm up-/down-stream from COM and irradiated with 5 different doses (2–10 Gy) using 10-cm-SOBP 160-MeV protons. After irradiation, films were cleaned and read to determine the delivered dose. A vial containing spherical GNPs (20 mg Au/g) was also irradiated, and gamma-rays from activation products were measured using a cadmium-telluride (CdTe) detector. Results: Film measurements showed no significant dose enhancement beyond the experimental uncertainty (∼2%). There was a detectable activation product from GNPs, but it appeared to contribute to dose enhancement minimally (<0.01%). Conclusion: Considering the composition of EBT2 film, it can be inferred that gold characteristic x-rays from PIXE and their secondary electrons make insignificant contribution to dose enhancement. The current investigation also suggests negligible dose enhancement due to activation products. Thus, previously-reported GNP-mediated proton dose enhancement/radiosensitization needs to be attributed to one or more of the other mechanisms listed earlier. Supported in part by NIH/NCI grant R01CA155446;This investigation was supported in part by NIH/NCI grant R01CA155446.« less
  • Purpose: Brachytherapy Application with in-situ Dose-painting Administered via Gold-Nanoparticle Eluters (BANDAGE) has been proposed as a new therapeutic strategy for radiation boosting of high-risk prostate tumor subvolume while minimizing dose to neighboring organs-at-risk. In a previous study the one-dimensional dose-painting with gold nanoparticles (GNP) released from GNP-loaded brachytherapy spacers was investigated. The current study investigates BANDAGE in three-dimensions. Methods: To simulate GNPs transport in prostrate tumors, a three dimensional, cylindrically symmetric transport model was generated using a finite element method (FEM). A mathematical model of Gold nanoparticle (GNPs) transport provides a useful strategy to optimize potential treatment planning for BANDAGE.more » Here, treatment of tumors with a radius of 2.5 cm was simulated in 3-D. This simulation phase considered one gold based cylindrical spacer (GBS of size 5mm × 0.8 mm) introduced at the center of the spherical tumor with initial concentration of 100 mg/g or 508 mol/m3 of GNP. Finite element mesh is used to stimulate the GNP transport. Gold concentrations within the tumor were obtained using a 3-D FEM solution implemented by COMSOL. Results: The analysis shows the spread of the GNPs through-out the tumor with the increase of concentration towards the periphery with time. The analysis also shows the concentration profiles and corresponding dose enhancement factors (dose boost factor) as a function of GNP size. Conclusion: This study demonstrates the use of computational modeling and optimal parameter estimation to predict local GNPs from central implant as a function of x, y and z axis . Such a study provides a useful reference for ongoing translational studies for the BANDAGE approach.« less
  • Purpose: Dose escalation strategy for lung cancer patients can lead to late symptoms such as pneumonitis and cardiac injury. We propose a strategy to increase radiation dose for improving local tumor control while simultaneously striving to minimize the injury of organs at risk (OAR). Our strategy is based on defining a small, biologically-guided target volume for receiving additional radiation dose. Methods: 106 patients with lung cancer treated with radiotherapy were selected for patients diagnosed with stage II and III disease. Previous research has shown that 50% of the maximum SUV threshold in FDG-PET imaging is appropriate for delineation of themore » most aggressive part of a tumor. After PET- and CT-derived targets were contoured, an IMRT treatment plan was designed to deliver 60 Gy to the GTV as delineated on a 4D CT (Plan 1). A second plan was designed with additional dose of 18 Gy to the PET-derived volume (Plan 2). A composite plan was generated by the addition of Plan 1 and Plan 2. Results: Plan 1 was compared to the composite plan and increases in OAR dose were assessed. For seven patients on average, lung V5 was increased by 1.4% and V20 by 4.2% for ipsilateral lung and by 13.5% and 7% for contralateral lung. For total lung, V5 and V20 were increased by 4.5% and 4.8% respectively. Mean lung dose was increased by 9.7% for the total lung. The maximum dose to the spinal cord increased by 16% on average. For the heart, V20 increased by 4.2% and V40 by 5.2%. Conclusion: It seems feasible that an additional 18 Gy of radiation dose can be delivered to FDG PET-derived subvolume of the CT-based GTV of the primary tumor without significant increase in total dose to the critical organs such as lungs, spinal cord and heart.« less
  • Purpose: To evaluate the impact of dose calculation algorithm on the dose distribution of biologically optimized Volumatric Modulated Arc Therapy (VMAT) plans for Esophgeal cancer. Methods: Eighteen retrospectively treated patients with carcinoma esophagus were studied. VMAT plans were optimized using biological objectives in Monaco (5.0) TPS for 6MV photon beam (Elekta Infinity). These plans were calculated for final dose using Monte Carlo (MC), Collapsed Cone Convolution (CCC) & Pencil Beam Convolution (PBC) algorithms from Monaco and Oncentra Masterplan TPS. A dose grid of 2mm was used for all algorithms and 1% per plan uncertainty maintained for MC calculation. MC basedmore » calculations were considered as the reference for CCC & PBC. Dose volume histogram (DVH) indices (D95, D98, D50 etc) of Target (PTV) and critical structures were compared to study the impact of all three algorithms. Results: Beam models were consistent with measured data. The mean difference observed in reference with MC calculation for D98, D95, D50 & D2 of PTV were 0.37%, −0.21%, 1.51% & 1.18% respectively for CCC and 3.28%, 2.75%, 3.61% & 3.08% for PBC. Heart D25 mean difference was 4.94% & 11.21% for CCC and PBC respectively. Lung Dmean mean difference was 1.5% (CCC) and 4.1% (PBC). Spinal cord D2 mean difference was 2.35% (CCC) and 3.98% (PBC). Similar differences were observed for liver and kidneys. The overall mean difference found for target and critical structures was 0.71±1.52%, 2.71±3.10% for CCC and 3.18±1.55%, 6.61±5.1% for PBC respectively. Conclusion: We observed a significant overestimate of dose distribution by CCC and PBC as compared to MC. The dose prediction of CCC is closer (<3%) to MC than that of PBC. This can be attributed to poor performance of CCC and PBC in inhomogeneous regions around esophagus. CCC can be considered as an alternate in the absence of MC algorithm.« less
  • Purpose: This study is to investigate the effects of the gold nanoparticles (GNP), a series of micrometre scale simulations have been constructed with Geant4 to track particles and simulate the effects of those particles as they pass through water phantom. Methods: The simulations were used to calculate the number of secondary electrons which are emitted from the particle tracks and the amount of energy which is deposited in the cell tissue. More electrons means that more water molecules can undergo hydrolysis and create potentially dangerous free radical molecules, therefore breaking up DNA and killing off cells or causing damaging mutations.more » Results: For the 20nm GNP, all three proton energies saw a small increase of electrons above the control, while the X-rays nearly tripled the number of electrons in the phantom. For the 50 nm GNP, the 3 and 2 MeV protons saw a small increase again, however the 1 MeV protons saw a decrease in electrons, the X-rays saw a large increase of nearly 4 times the number of electrons. For the 110nm GNP, all three proton energies saw a decrease in the total number of electrons in the phantom, while the X-rays saw an increase of 8 times as many electrons. Conclusion: From the range of GNP sizes used, it was found that the X-rays have a larger dose enhancement effect as the GNP size increases, the relation between electron emissions and GNP size was linear. This is because the majority of the dose from the X-rays is delivered to the cell tissue through the initial high energy secondary electrons, any dose lost from the Augerelectrons being trapped inside the GNP volume is small compared to the dose that escapes with the high energy electrons.« less