Heterogeneous multiscale Monte Carlo simulations for gold nanoparticle radiosensitization

Martinov, Martin P.; Thomson, Rowan M.

doi:10.1002/mp.12061

Cited by 40 publications

(94 citation statements)

References 40 publications

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“…The transport cutoff and production threshold for the kinetic energy of electrons and photons is 1 keV. The application of EGSnrc/egs_chamber to score specific energy within microscopic targets has been discussed previously 41,15,42 . Results demonstrated insensitivity to transport parameters; in particular, results were unaffected by increasing the electron transport cutoff from 1 to 2 keV in 0.25 keV increments.…”

Section: B Monte Carlo Simulationsmentioning

confidence: 99%

Investigating energy deposition in glandular tissues for mammography using multiscale Monte Carlo simulations

Oliver

Thomson

2019

Medical Physics

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Purpose To investigate energy deposition in glandular tissues of the breast on macro‐ and microscopic length scales in the context of mammography. Methods Multiscale mammography models of breasts are developed, which include segmented, voxelized macroscopic tissue structure as well as nine regions of interest (ROIs) embedded throughout the breast tissue containing explicitly‐modelled cells. Using a 30 kVp Mo/Mo spectrum, Monte Carlo (MC) techniques are used to calculate dose to ∼mm voxels containing glandular and/or adipose tissues, as well as energy deposition on cellular length scales. ROIs consist of at least 1000 mammary epithelial cells and ∼200 adipocytes; specific energy (energy imparted per unit mass; stochastic analogue of the absorbed dose) is calculated within mammary epithelial cell nuclei. Results Macroscopic dose distributions within segmented breast tissue demonstrate considerable variation in energy deposition depending on depth and tissue structure. Doses to voxels containing glandular tissue vary between ∼0.1 and ∼4 times the mean glandular dose (MGD, averaged over the entire breast). Considering microscopic length scales, mean specific energies for mammary epithelial cell nuclei are ∼30% higher than the corresponding glandular voxel dose. Additionally, due to the stochastic nature of radiation, there is considerable variation in energy deposition throughout a cell population within a ROI: for a typical glandular voxel dose of 4 mGy, the standard deviation of the specific energy for mammary epithelial cell nuclei is 85% relative to the mean. Thus, for a glandular voxel dose of 4 mGy at the centre of the breast, corresponding mammary epithelial cell nuclei will receive specific energies up to ∼9 mGy (considering the upper end of the 1σ standard deviation of the specific energy), while a ROI located 2 cm closer to the radiation source will receive specific energies up to ∼40 mGy. Energy deposition within mammary epithelial cell nuclei is sensitive to cell model details including cellular elemental compositions and nucleus size, underlining the importance of realistic cellular models. Conclusions There is considerable variation in energy deposition on both macro‐ and microscopic length scales for mammography, with glandular voxel doses and corresponding cell nuclei specific energies many times higher than the MGD in parts of the breast. These results should be considered for radiation‐induced cancer risk evaluation in mammography which has traditionally focused on a single metric such as the MGD.

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Section: B Monte Carlo Simulationsmentioning

confidence: 99%

Investigating energy deposition in glandular tissues for mammography using multiscale Monte Carlo simulations

Oliver

Thomson

2019

Medical Physics

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“…This behavior can potentially have repercussions in many clinical scenarios where the accumulation of dose from nonlocal GNPs is relied upon as a means of dose enhancement to boost a desired biological effect. It is also important to keep this in mind in the larger scale context as well, where attenuation of low‐energy beams through a medium containing GNPs may not be insignificant …”

Section: Discussionmentioning

confidence: 99%

“…This suggests that the position of each GNP relative to sensitive volumes within a given cell can play a critical role in determining that cell's response when irradiated. Hence, there is a problem of dose calculation on multiple scales . One way to address this is by separating the problem into macroscopic and microscopic components and superimposing the microscopic dose from each GNP onto a macroscopic background as outlined by Kirkby and Ghasroddashti .…”

Section: Methodsmentioning

confidence: 99%

Dosimetric consequences of gold nanoparticle clustering during photon irradiation

et al. 2017

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“…In a mouse model of malignant glioma, the one-year survival was 86% with AuNP-augmented RT versus 20% with RT alone and 0% with AuNPs alone 17 . Monte Carlo simulations and biological studies have estimated that the radiation dose enhancement due to gold nanoparticles can vary from 10% up to 500% for orthovoltage x-rays, depending on the nanoparticle size, concentration, and other experimental parameters 22 - 25 . A majority of studies, however, demonstrate a radiation dose enhancement of between 40% and 80% in the presence of gold nanoparticles 26 .…”

Section: Introductionmentioning

confidence: 99%

Dual-Energy CT Imaging of Tumor Liposome Delivery After Gold Nanoparticle-Augmented Radiation Therapy

Ashton¹,

Castle²,

Qi³

et al. 2018

Theranostics

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Gold nanoparticles (AuNPs) are emerging as promising agents for both cancer therapy and computed tomography (CT) imaging. AuNPs absorb x-rays and subsequently release low-energy, short-range photoelectrons during external beam radiation therapy (RT), increasing the local radiation dose. When AuNPs are near tumor vasculature, the additional radiation dose can lead to increased vascular permeability. This work focuses on understanding how tumor vascular permeability is influenced by AuNP-augmented RT, and how this effect can be used to improve the delivery of nanoparticle chemotherapeutics.Methods: Dual-energy CT was used to quantify the accumulation of both liposomal iodine and AuNPs in tumors following AuNP-augmented RT in a mouse model of primary soft tissue sarcoma. Mice were injected with non-targeted AuNPs, RGD-functionalized AuNPs (vascular targeting), or no AuNPs, after which they were treated with varying doses of RT. The mice were injected with either liposomal iodine (for the imaging study) or liposomal doxorubicin (for the treatment study) 24 hours after RT. Increased tumor liposome accumulation was assessed by dual-energy CT (iodine) or by tracking tumor treatment response (doxorubicin).Results: A significant increase in vascular permeability was observed for all groups after 20 Gy RT, for the targeted and non-targeted AuNP groups after 10 Gy RT, and for the vascular-targeted AuNP group after 5 Gy RT. Combining targeted AuNPs with 5 Gy RT and liposomal doxorubicin led to a significant tumor growth delay (tumor doubling time ~ 8 days) compared to AuNP-augmented RT or chemotherapy alone (tumor doubling time ~3-4 days).Conclusions: The addition of vascular-targeted AuNPs significantly improved the treatment effect of liposomal doxorubicin after RT, consistent with the increased liposome accumulation observed in tumors in the imaging study. Using this approach with a liposomal drug delivery system can increase specific tumor delivery of chemotherapeutics, which has the potential to significantly improve tumor response and reduce the side effects of both RT and chemotherapy.

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Heterogeneous multiscale Monte Carlo simulations for gold nanoparticle radiosensitization

Cited by 40 publications

References 40 publications

Investigating energy deposition in glandular tissues for mammography using multiscale Monte Carlo simulations

Investigating energy deposition in glandular tissues for mammography using multiscale Monte Carlo simulations

Dosimetric consequences of gold nanoparticle clustering during photon irradiation

Dual-Energy CT Imaging of Tumor Liposome Delivery After Gold Nanoparticle-Augmented Radiation Therapy

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