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Title: SU-G-TeP3-13: The Role of Nanoscale Energy Deposition in the Development of Gold Nanoparticle-Enhanced Radiotherapy

Abstract

Purpose: Gold nanoparticles (GNPs) can enhance radiotherapy effects. The high photoelectric cross section of gold relative to tissue, particularly at lower energies, leads to localized dose enhancement. However in a clinical context, photon energies must also be sufficient to reach a target volume at a given depth. These properties must be balanced to optimize such a therapy. Given that nanoscale energy deposition patterns around GNPs play a role in determining biological outcomes, in this work we seek to establish their role in this optimization process. Methods: The PENELOPE Monte Carlo code was used to generate spherical dose deposition kernels in 1000 nm diameter spheres around 50 nm diameter GNPs in response to monoenergetic photons incident on the GNP. Induced “lesions” were estimated by either a local effect model (LEM) or a mean dose model (MDM). The ratio of these estimates was examined for a range of photon energies (10 keV to 2 MeV), for three sets of linear-quadratic parameters. Results: The models produce distinct differences in expected lesion values, the lower the alpha-beta ratio, the greater the difference. The ratio of expected lesion values remained constant within 5% for energies of 40 keV and above across all parameter sets andmore » rose to a difference of 35% for lower energies only for the lowest alpha-beta ratio. Conclusion: Consistent with other work, these calculations suggest nanoscale energy deposition patterns matter in predicting biological response to GNP-enhanced radiotherapy. However the ratio of expected lesions between the different models is largely independent of energy, indicating that GNP-enhanced radiotherapy scenarios can be optimized in photon energy without consideration of the nanoscale patterns. Special attention may be warranted for energies of 20 keV or below and low alpha-beta ratios.« less

Authors:
 [1];  [2];  [3];  [4];  [5]
  1. Jack Ady Cancer Centre, Lethbridge, AB (Canada)
  2. (Canada)
  3. The University of Calgary, Calgary, AB (Canada)
  4. Chris O’Brien Lifehouse Camperdown, NSW (Australia)
  5. University of Sydney, Sydney, NSW (Australia)
Publication Date:
OSTI Identifier:
22649434
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:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; DEPOSITION; ENERGY ABSORPTION; ENERGY LOSSES; GOLD; KEV RANGE 01-10; KEV RANGE 10-100; MEV RANGE 01-10; MONTE CARLO METHOD; NANOPARTICLES; NANOSTRUCTURES; PHOTONS; RADIATION DOSES; RADIOTHERAPY; SPHERICAL CONFIGURATION

Citation Formats

Kirkby, C, The University of Calgary, Calgary, AB, Koger, B, Suchowerska, N, and McKenzie, D. SU-G-TeP3-13: The Role of Nanoscale Energy Deposition in the Development of Gold Nanoparticle-Enhanced Radiotherapy. United States: N. p., 2016. Web. doi:10.1118/1.4957093.
Kirkby, C, The University of Calgary, Calgary, AB, Koger, B, Suchowerska, N, & McKenzie, D. SU-G-TeP3-13: The Role of Nanoscale Energy Deposition in the Development of Gold Nanoparticle-Enhanced Radiotherapy. United States. doi:10.1118/1.4957093.
Kirkby, C, The University of Calgary, Calgary, AB, Koger, B, Suchowerska, N, and McKenzie, D. 2016. "SU-G-TeP3-13: The Role of Nanoscale Energy Deposition in the Development of Gold Nanoparticle-Enhanced Radiotherapy". United States. doi:10.1118/1.4957093.
@article{osti_22649434,
title = {SU-G-TeP3-13: The Role of Nanoscale Energy Deposition in the Development of Gold Nanoparticle-Enhanced Radiotherapy},
author = {Kirkby, C and The University of Calgary, Calgary, AB and Koger, B and Suchowerska, N and McKenzie, D},
abstractNote = {Purpose: Gold nanoparticles (GNPs) can enhance radiotherapy effects. The high photoelectric cross section of gold relative to tissue, particularly at lower energies, leads to localized dose enhancement. However in a clinical context, photon energies must also be sufficient to reach a target volume at a given depth. These properties must be balanced to optimize such a therapy. Given that nanoscale energy deposition patterns around GNPs play a role in determining biological outcomes, in this work we seek to establish their role in this optimization process. Methods: The PENELOPE Monte Carlo code was used to generate spherical dose deposition kernels in 1000 nm diameter spheres around 50 nm diameter GNPs in response to monoenergetic photons incident on the GNP. Induced “lesions” were estimated by either a local effect model (LEM) or a mean dose model (MDM). The ratio of these estimates was examined for a range of photon energies (10 keV to 2 MeV), for three sets of linear-quadratic parameters. Results: The models produce distinct differences in expected lesion values, the lower the alpha-beta ratio, the greater the difference. The ratio of expected lesion values remained constant within 5% for energies of 40 keV and above across all parameter sets and rose to a difference of 35% for lower energies only for the lowest alpha-beta ratio. Conclusion: Consistent with other work, these calculations suggest nanoscale energy deposition patterns matter in predicting biological response to GNP-enhanced radiotherapy. However the ratio of expected lesions between the different models is largely independent of energy, indicating that GNP-enhanced radiotherapy scenarios can be optimized in photon energy without consideration of the nanoscale patterns. Special attention may be warranted for energies of 20 keV or below and low alpha-beta ratios.},
doi = {10.1118/1.4957093},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = 2016,
month = 6
}
  • 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
  • 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: This study investigated the dose enhancement effect of using gold nanoparticles (GNP) as radiation sensitizers radiated by different photon beam energies. Microdosimetry of photon-irradiated GNP was determined by the Geant4-DNA process in the DNA scale. Methods: Monte Carlo simulation was conducted using the Geant4 toolkit (ver. 10.2). A GNP with different sizes (30, 50, and 100nm diameter sphere) and a DNA were placed in a water cube (1µm{sup 3}). The GNP was irradiated by photon beams with different energies (50, 100, and 150keV) and produced secondary electrons to increase the dose to the DNA. Energy depositions were calculated formore » both with and without GNP and to investigate the dose enhancement effect at the DNA. The distance between the GNP and DNA was varied to optimize the best GNP position to the DNA. The photon beam source was set to 200nm from the GNP in each simulation. Results: It is found that GNP had a dose enhancement effect on kV photon radiations. For Monte Carlo results on different GNP sizes, distances between the GNP and DNA, and photon beam energies, enhancement ratio was found increasing as GNP size increased. The distance between the GNP and DNA affected the result that as distance increased while the dose enhancement ratio decreased. However, the effect of changing distance was not as significant as varying the GNP size. In addition, increasing the photon beam energy also increased the dose enhancement ratio. The largest dose enhancement ratio was found to be 3.5, when the GNP (100nm diameter) irradiated by the 150keV photon beam was set to 80nm from the DNA. Conclusion: Dose enhancement was determined in the DNA with GNP in the microdosimetry scale. It is concluded that the dose enhancement varied with the photon beam energy, GNP size and distance between the GNP and DNA.« less
  • Purpose: This study investigates the feasibility of exploiting the Cerenkov radiation (CR) present during external beam radiotherapy (EBRT) for significant therapeutic gain, using titanium dioxide nanoparticles (titania) delivered via a new design of radiotherapy biomaterials. Methods: Recently published work has shown that CR generated by radionuclides during PET imaging could substantially enhance damage to cancer cells in the presence of 0.625 µg/g titania. We hypothesize that equal or greater damage can be achieved during EBRT. To test this hypothesis, Monte Carlo simulation was done using GEANT4 in order to get the total CR yield inside a tumor volume during EBRTmore » compared to that of the radionuclides. We considered a novel approach where a sufficiently potent concentration of the titania was delivered directly into the tumor using radiotherapy biomaterials (e.g. fiducials) loaded with the titania. The intra-tumor distribution/diffusion of titania released from the fiducials was calculated. An in-vitro MTS assay experiment was also carried out to establish the relative non-toxicity of titania for concentrations of up to 1 µg/g. Results: For a radiotherapy biomaterial loaded with 15 µg/g of 2-nm titania, at least 0.625 µg/g could be delivered through out a tumor sub-volume of 2-cm diameter after 14 days. This concentration level could inflict substantial damage to tumor cells during EBRT. The Monte Carlo results showed the CR yield in tumor by 6 MV radiation was higher than the radionuclides and hence potentially greater damage may be obtained during EBRT. No significant cell viability change was observed for 1 µg/g titania. Conclusion: Altogether, these preliminary findings demonstrate a potential new approach that can be used to take advantage of the CR present during megavoltage EBRT to boost damage to tumor cells. The results provide significant impetus for further experimental studies towards development of nanoparticle-aided EBRT powered by the Cerenkov effect.« less
  • Introduction: The use of gold nanoparticles (GNPs) in radiotherapy has shown promise for therapeutic enhancement. In this study, we explore the feasibility of enhancing radiotherapy with GNPs in an arc-therapy context. We use Monte Carlo simulations to quantify the macroscopic dose-enhancement ratio (DER) and tumour to normal tissue ratio (TNTR) as functions of photon energy over various tumour and body geometries. Methods: GNP-enhanced arc radiotherapy (GEART) was simulated using the PENELOPE Monte Carlo code and penEasy main program. We simulated 360° arc-therapy with monoenergetic photon energies 50 – 1000 keV and several clinical spectra used to treat a spherical tumourmore » containing uniformly distributed GNPs in a cylindrical tissue phantom. Various geometries were used to simulate different tumour sizes and depths. Voxel dose was used to calculate DERs and TNTRs. Inhomogeneity effects were examined through skull dose in brain tumour treatment simulations. Results: Below 100 keV, DERs greater than 2.0 were observed. Compared to 6 MV, tumour dose at low energies was more conformai, with lower normal tissue dose and higher TNTRs. Both the DER and TNTR increased with increasing cylinder radius and decreasing tumour radius. The inclusion of bone showed excellent tumour conformality at low energies, though with an increase in skull dose (40% of tumour dose with 100 keV compared to 25% with 6 MV). Conclusions: Even in the presence of inhomogeneities, our results show promise for the treatment of deep-seated tumours with low-energy GEART, with greater tumour dose conformality and lower normal tissue dose than 6 MV.« less