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Title: TU-H-CAMPUS-TeP3-03: Dose Enhancement by Gold Nanoparticles Around the Bragg Peak of Proton Beams

Abstract

Purpose: To make clear the spatial distribution of dose enhancement around gold nanoparticles (GNPs) located near the proton Bragg peak, and to evaluate the potential of GNPs as a radio sensitizer. Methods: The dose enhancement by electrons emitted from GNPs under proton irradiation was estimated by Geant4 Monte Carlo simulation toolkit in two steps. In an initial macroscopic step, 100 and 195 MeV proton beams were incident on a water cube, 30 cm on a side. Energy distributions of protons were calculated at four depths, 50% and 75% proximal to the Bragg peak, 100% peak, and 75% distal to the peak (P50, P75, Peak, and D75, respectively). In a subsequent microscopic step, protons with the energy distribution calculated above were incident on a 20 nm diameter GNP in a nanometer-size water box and the spatial distribution of dose around the GNP was determined for each energy distribution. The dose enhancement factor (DEF) was also deduced. Results: The dose enhancement effect was spread to several tens of nanometers in the both depth and radial directions. The enhancement area increased in the order of P50, P75, Peak, and D75 for both cases with 100 and 195 MeV protons. In every position aroundmore » the Bragg peak, the 100 MeV beam resulted in a higher dose enhancement than the 195 MeV beam. At P75, the average and maximum DEF were 3.9 and 17.0 for 100 MeV, and 3.5 and 16.2 for 195 MeV, respectively. These results indicate that lower energy protons caused higher dose enhancement in this incident proton energy range. Conclusion: The dose enhancement around GNPs spread as the position in the Bragg peak region becomes deeper and depends on proton energy. It is expected that GNPs can be used as a radio sensitizer with consideration of the location and proton beam energy.« less

Authors:
;  [1];  [2]; ;  [3];  [4];  [5]
  1. Department of Medical Physics, Hokkaido University Graduate School of Medicine (Japan)
  2. Department of Radiation Medicine, Hokkaido University Graduate School of Medicine (Japan)
  3. Department of Radiation Oncology, Stanford University and Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University (Japan)
  4. Department of Radiation Medicine, Hokkaido University Graduate School of Medicine and Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University (Japan)
  5. Faculty of Health Sciences, Hokkaido University (Japan)
Publication Date:
OSTI Identifier:
22654079
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
61 RADIATION PROTECTION AND DOSIMETRY; 60 APPLIED LIFE SCIENCES; BRAGG CURVE; COMPUTERIZED SIMULATION; ENERGY SPECTRA; MEV RANGE 100-1000; MEV RANGE 10-100; MONTE CARLO METHOD; NANOPARTICLES; PEAKS; PROTON BEAMS; RADIATION DOSES; SPATIAL DISTRIBUTION

Citation Formats

Kwon, J, Sutherland, K, Hashimoto, T, Peng, H, Xing, L, Shirato, H, and Date, H. TU-H-CAMPUS-TeP3-03: Dose Enhancement by Gold Nanoparticles Around the Bragg Peak of Proton Beams. United States: N. p., 2016. Web. doi:10.1118/1.4957706.
Kwon, J, Sutherland, K, Hashimoto, T, Peng, H, Xing, L, Shirato, H, & Date, H. TU-H-CAMPUS-TeP3-03: Dose Enhancement by Gold Nanoparticles Around the Bragg Peak of Proton Beams. United States. doi:10.1118/1.4957706.
Kwon, J, Sutherland, K, Hashimoto, T, Peng, H, Xing, L, Shirato, H, and Date, H. Wed . "TU-H-CAMPUS-TeP3-03: Dose Enhancement by Gold Nanoparticles Around the Bragg Peak of Proton Beams". United States. doi:10.1118/1.4957706.
@article{osti_22654079,
title = {TU-H-CAMPUS-TeP3-03: Dose Enhancement by Gold Nanoparticles Around the Bragg Peak of Proton Beams},
author = {Kwon, J and Sutherland, K and Hashimoto, T and Peng, H and Xing, L and Shirato, H and Date, H},
abstractNote = {Purpose: To make clear the spatial distribution of dose enhancement around gold nanoparticles (GNPs) located near the proton Bragg peak, and to evaluate the potential of GNPs as a radio sensitizer. Methods: The dose enhancement by electrons emitted from GNPs under proton irradiation was estimated by Geant4 Monte Carlo simulation toolkit in two steps. In an initial macroscopic step, 100 and 195 MeV proton beams were incident on a water cube, 30 cm on a side. Energy distributions of protons were calculated at four depths, 50% and 75% proximal to the Bragg peak, 100% peak, and 75% distal to the peak (P50, P75, Peak, and D75, respectively). In a subsequent microscopic step, protons with the energy distribution calculated above were incident on a 20 nm diameter GNP in a nanometer-size water box and the spatial distribution of dose around the GNP was determined for each energy distribution. The dose enhancement factor (DEF) was also deduced. Results: The dose enhancement effect was spread to several tens of nanometers in the both depth and radial directions. The enhancement area increased in the order of P50, P75, Peak, and D75 for both cases with 100 and 195 MeV protons. In every position around the Bragg peak, the 100 MeV beam resulted in a higher dose enhancement than the 195 MeV beam. At P75, the average and maximum DEF were 3.9 and 17.0 for 100 MeV, and 3.5 and 16.2 for 195 MeV, respectively. These results indicate that lower energy protons caused higher dose enhancement in this incident proton energy range. Conclusion: The dose enhancement around GNPs spread as the position in the Bragg peak region becomes deeper and depends on proton energy. It is expected that GNPs can be used as a radio sensitizer with consideration of the location and proton beam energy.},
doi = {10.1118/1.4957706},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = {Wed Jun 15 00:00:00 EDT 2016},
month = {Wed Jun 15 00:00:00 EDT 2016}
}
  • Purpose: To probe physical evidences of the dose enhancement due to a low/clinically-relevant concentration of gold nanoparticles (GNPs) and Yb-169 gamma rays using PRESAGE dosimeters. Methods: A PRESAGE cuvette was placed at approximately 2 mm above the plane containing three novel Yb-169 brachytherapy seeds (3.2, 3.2, and 5.3 mCi each). Two types of PRESAGE dosimeters were used – plain PRESAGEs (controls) and PRESAGEs loaded with 0.02 wt. % of GNPs (GNP-PRESAGEs). Each PRESAGE dosimeter was irradiated with different time durations (0 to 24 hours) to deliver 0, 4, 8, 16 and 24 Gy of dose. For a reference/comparison, both typesmore » of PRESAGEs were also irradiated using 250 kVp x-rays with/without Er-filter to deliver 0, 3, 10, and 30 Gy of dose. Er-filter was used to emulate Yb-169 spectrum using 250 kVp x-rays. The absorption spectra of PRESAGEs were measured using a UV spectrophotometer and used to determine the corresponding optical densities (ODs). Results: GNP-PRESAGEs exposed to Yb-169 sources showed ∼65% increase in ODs compared with controls. When exposed to Er-filtered and unfiltered 250 kVp x-rays, they produced smaller increases in ODs, ∼41% and ∼37%, respectively. There was a linear relationship between ODs and delivered doses with a goodness-of-fit (R2) greater than 0.99. Conclusion: A notable increase in the ODs (∼65%) was observed for GNP-PRESAGEs irradiated by Yb-169 gamma rays. Considering the observed OD increases, it was highly likely that Yb-169 gamma rays were more effective than both Er-filtered and unfiltered 250 kVp x-rays, in terms of producing the dose enhancement. Due to several unknown factors (e.g., possible difference in the dose response of GNP-PRESAGEs vs. PRESAGEs), however, a further investigations is necessary to establish the feasibility of quantifying the exact amount of macroscopic or microscopic/local GNP-mediated dose enhancement using PRESAGE or similar volumetric dosimeters. Supported by DOD/PCRP grant W81XWH-12-1-0198 This investigation was supported by DOD/PCRP grant W81XWH-12-1-0198.« less
  • Purpose: Recent studies have shown that the presence of Gold Nanoparticles (GNPs) in tumor tissue can lead to significant dose enhancement (DE) during External Beam Radiation Therapy (EBRT). In this in-silico study we investigate EBRT with in-situ dose painting using GNPs released from cylindrically shaped GNP-loaded fiducials. Methods: Reported Biologically Target/Tumor Volumes (BTVs) for 12 prostate carcinoma patients were employed in this study. Distribution of the GNPs after burst release from the fiducial (1.5mm diameter and 5mm length) located in the center of the spherically assumed BTV were modeled by isotropic and free diffusion without boundary condition and under themore » assumption of superposition. An experimentally determined diffusion coefficient for 10nm nanoparticles was adapted for investigating other GNP sizes (2, 5, 15, and 20nm) using the Stokes-Einstein equation. The maximum size of GNPs to achieve a minimal DE Factor (DEF) of 1.1 for 6MV EBRT using a fiducial-load of 30mg/g was calculated for typical periods of 14 and 21 days after implantation. Further, the minimal fiducial-load needed to achieve a clinically significant DEF of 1.2 was computed for 2nm GNPs. Results: Results showed that a minimal DEF of 1.1 could be reached for the smallest patient BTV using a maximal GNP size of 10nm and 20nm after 14 and 21 days, respectively. With increasing BTV smaller GNPs are required to ensure the same DEF. In particular, the largest BTV requires 2nm GNPs for periods of 14 and 21 days. Meanwhile, the required fiducial-load to reach a minimal DEF of 1.2 after 14 days was found in the range of 17mg/g and 59mg/g for all reported BTVs. Conclusion: This preliminary study indicates a strong dependence on GNP size and fiducial-load to realize a significant DE. The findings avail further research towards development of GNP-loaded fiducials for significantly enhancing radiotherapy for cancer patients.« less
  • Purpose: The aim of this study is to apply Monte Carlo simulations to investigate the nanoparticle dose enhancement for Auger therapy. Methods: Two nanoparticle fabrications were considered: nanoshell and nanosphere. In the first step, a single nanoparticle was irradiated with Auger emitters. The electrons were scored in a phase space at the outer surface of the nanoparticle with Geant4-Penelope. In the second step, the previously recorded phase space was used as a source and placed at the center of a cell-size water phantom. The nanoscale dose was evaluated in water around the nanoparticle with Geant4-DNA. The dose enhancement factor (DEF)more » is defined as the ratio of doses with and without nanoparticles. The nanoparticles were replaced by corresponding water nanoparticle with the same size and volume source which represents typical situation of Auger emitters without nanoparticle. Various sizes/materials of nanoparticles and isotopes were considered. Results: Nanoshell - Microscopic dose was increased up to 130% at 20 – 100 nm distances from the surface of Au-{sup 125}I nanoshell. However, dose at less than 20 nm distance was reduced due to absorbed low energy electrons in gold nanoshell. The amounts and regions of the dose enhancement were dependent on nanoshell size, materials, and isotopes. Nanosphere - The increased amounts of electrons up to 300% and reduced average energy with nanosphere were observed compared with water nanoparticle. We observed localized dose enhancement (up to a factor 3.6) in the immediate vicinity (< 50 nm) of Au-{sup 125} I nanosphere. The dose enhancement patterns vary according to nanosphere sizes and isotopes. Conclusion: We conclude that Auger therapy with nanoparticles can lead to change of electron energy spectrum and dose enhancements at certain range. The dose enhancement patterns vary according to nanoparticle sizes, materials, and isotopes. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP: Ministry of Science, ICT and Future Planning) (No. NRF-2013M2B2B1075776)« less
  • Purpose: Gold nanoparticle (GNP) is a promising radiosensitizer that selectively boosts tumor dose in radiotherapy. Transmission electron microscopy (TEM) imaging observations recently revealed for the first time that GNP exists in vivo in the form of highly localized vesicles, instead of hypothetical uniform distribution. This work investigates the corresponding difference of energy deposition in proton therapy. Methods: First, single vesicles of various radii were constructed by packing GNPs (as Φ50 nm gold spheres) in spheres and were simulated, as well as a single GNP. The radial energy depositions (REDs) were scored using 100 concentric spherical shells from 0.1µm to 10µm,more » 0.1µm thickness each, for both vesicles and GNP, and compared. TEM images, 8 days after injection in a PC3 prostate cancer murine model, were used to extract position/dimension of vesicles, as well as contours of cytoplasmic and nucleus membranes. Vesicles were then constructed based on the TEM images. A 100 MeV proton beam was studied by using the Geant4-DNA code, which simulates all energy deposition events. Results: The vesicle REDs, normalized to the same proton energy loss as in a single GNP, are larger (smaller) than that of a single GNP when radius >2µm (<2µm). The peak increase (at about 3µm radius) is about 10% and 18% for Φ1µm and Φ1.6µm vesicles respectively, relative to a single GNP. The TEM-based simulation resulted in a larger energy deposition (by about one order of magnitude) that follows completely different pattern from that of hypothetical GNP distributions (regular dotted pattern in extracellular and/or extranucleus regions). Conclusion: The in vivo energy deposition, both in pattern and magnitude, of proton therapy is greatly affected by the true distribution of the GNP, as illustrated by the presence of GNP vesicles compared to hypothetical scenarios. Work supported by NSERC Discovery Grant #435510, Canada.« less
  • Purpose: To measure the increase in in vitro radiosensitivity for A549 lung carcinoma cells due to gold nanoparticle (GNP) radiation dose enhancement in both traditional monolayer and three dimensional (3D) cell culture models. Methods: A γH2AX immunofluorescence assay is performed on monolayer A549 cell culture and quantitatively analyzed to measure the increase in double strand breaks (DSBs) resulting from GNP dose enhancement. A clonogenic survival assay (CSA) is then performed on monolayer A549 cell culture to assess true viability after treatment. And lastly, another γH2AX assay is performed on 3D A549 multicellular nodules overlaid on a bed of growth factormore » reduced matrigel to measure dose response in a model that better recapitulates treatment response to actual tumors in vivo. Results: The first γH2AX assay performed on the monolayer cell culture shows a significant increase in DSBs due to GNP dose enhancement. The maximum average observed increase in normalized fluorescent intensity for monolayer cell culture is 171% for the 6Gy-treatment groups incubated in 0.556 mg Au/ml solution. The CSA performed on monolayer cell culture also shows considerable GNP dose enhancement. The maximum decrease in the normalized surviving fraction is 12% for the 4Gy-treatment group incubated in 0.556 mg Au/ml. And lastly, the GNP dose enhancement is confirmed to be mitigated in three dimensional cell culture models as compared to the traditional monolayer model. The maximum average observed dose enhancement for 3D cell culture is 19% for the 6Gy-treatment groups and incubated in 0.556 mg Au/ml. Conclusion: A marked increase in radiosensitivity is observed for A549 lung carcinoma cells when treated with GNPs plus radiation as opposed to radiation alone. Traditional monolayer cell culture also shows a much more pronounced radiation dose enhancement than 3D cell culture.« less