Gold Nanoparticle-aided Radiation Therapy Research Articles

Enhancement of radio-sensitivity of colorectal cancer cells by gold nanoparticles at 18 MV energy

Objective(s): Taking advantage of high atomic number of gold nanoparticles (GNPs) in radiation dose absorbing, many in vitro and in vivo studies have been carried out on using them as radio-sensitizer. In spite of noticeable dose enhancement by GNPs at keV energies, using this energy range for radiotherapy of deep-seated tumors is outdated. The aim of the present work was to examine the effect of GNPs on radio-sensitivity of HT-29 cells in combination with 18 MV X-rays.Materials and Methods: GNPs were synthesized using a seed-growth method and characterized by transmission electron microscopy (TEM) for size and morphology. Cytotoxicity effect of the GNPs as well as amount of uptake into the HT-29 cell line was assessed. Irradiation was done by 18 MV photons. Immuno-fluorescent imaging of γ-H2AX foci and clonogenic assay were conducted to find out the effect of the GNPs on radio-sensitivity of the cells.Results: The size of GNPs was about 24 nm with a spherical-like shape. Treatment of the cells with the GNPs induced insignificant inhibition in cell growth. Cellular uptake reaches a maximum after 12 h incubation with GNPs. Stained γ-H2AX foci showed a significant difference in number and intensity for GNPs treated cells compared to only irradiated one. Moreover, colony formation assay proved an impressive decrease in the number of colonies for the irradiated+GNPs group rather than the other one. By fitting the survival fraction data on the linear-quadratic model, sensitization enhancement factor (SER) of 1.25 was achieved.Conclusion: Although theoretical studies predicted negligible radio-enhancement factor for GNPs at high megavoltage energies, present results show the potential of GNPs for possible gold nanoparticle-aided radiation therapy (GNRT) even for high MV photons.

Technical Note: Monte Carlo calculations of the AAPM TG-43 brachytherapy dosimetry parameters for a new titanium-encapsulated Yb-169 source.

Due to a number of distinct advantages resulting from the relatively low energy gamma ray spectrum of Yb‐169, various designs of Yb‐169 sources have been developed over the years for brachytherapy applications. Lately, Yb‐169 has also been suggested as an effective and practical radioisotope option for a novel radiation treatment approach often known as gold nanoparticle‐aided radiation therapy (GNRT). In a recently published study, the current investigators used the Monte Carlo N‐Particle Version 5 (MCNP5) code to design a novel titanium‐encapsulated Yb‐169 source optimized for GNRT applications. In this study, the original MC source model was modified to accurately match the specifications of the manufactured Yb‐169 source. The modified MC model was then used to obtain a complete set of the AAPM TG‐43 parameters for the new titanium‐encapsulated Yb‐169 source. The MC‐calculated dose rate constant for this titanium‐encapsulated Yb‐169 source was 1.19 ± 0.03 cGy·h−1·U−1, indicating no significant change from the values reported for stainless steel‐encapsulated Yb‐169 sources. The source anisotropy and radial dose function for the new source were also found similar to those reported for the stainless steel‐encapsulated Yb‐169 sources. The current results suggest that the use of titanium, instead of stainless steel, to encapsulate the Yb‐169 core would not lead to any major change in the dosimetric characteristics of the Yb‐169 source. The results also show that the titanium encapsulation of the Yb‐169 source could be accomplished while meeting the design goals as described in the current investigators’ published MC optimization study for GNRT applications.

SU‐F‐T‐54: Determination of the AAPM TG‐43 Brachytherapy Dosimetry Parameters for A New Titanium‐Encapsulated Yb‐169 Source by Monte Carlo Calculations

Purpose:To determine the AAPM TG‐43 brachytherapy dosimetry parameters of a new titanium‐encapsulated Yb‐169 source designed to maximize the dose enhancement during gold nanoparticle‐aided radiation therapy (GNRT).Methods:An existing Monte Carlo (MC) model of the titanium‐encapsulated Yb‐169 source, which was described in the current investigators’ published MC optimization study, was modified based on the source manufacturer's detailed specifications, resulting in an accurate model of the titanium‐encapsulated Yb‐169 source that was actually manufactured. MC calculations were then performed using the MCNP5 code system and the modified source model, in order to obtain a complete set of the AAPM TG‐43 parameters for the new Yb‐169 source.Results:The MC‐calculated dose rate constant for the new titanium‐encapsulated Yb‐169 source was 1.05 ± 0.03 cGy per hr U, indicating about 10% decrease from the values reported for the conventional stainless steel‐encapsulated Yb‐169 sources. The source anisotropy and radial dose function for the new source were found similar to those reported for the conventional Yb‐169 sources.Conclusion:In this study, the AAPM TG‐43 brachytherapy dosimetry parameters of a new titanium‐encapsulated Yb‐169 source were determined by MC calculations. The current results suggested that the use of titanium, instead of stainless steel, to encapsulate the Yb‐169 core would not lead to any major change in the dosimetric characteristics of the Yb‐169 source, while it would allow more low energy photons being transmitted through the source filter thereby leading to an increased dose enhancement during GNRT. Supported by DOD/PCRP grant W81XWH‐12‐1‐0198This investigation was supported by DOD/PCRP grant W81XWH‐12‐1‐ 0198.

Gold Nanoparticle Mediated Phototherapy for Cancer

Gold nanoparticles exhibit very unique physiochemical and optical properties, which now are extensively studied in range of medical diagnostic and therapeutic applications. In particular, gold nanoparticles show promise in the advancement of cancer treatments. This review will provide insights into the four different cancer treatments such as photothermal therapy, gold nanoparticle-aided photodynamic therapy, gold nanoparticle-aided radiation therapy, and their use as drug carrier. We also discuss the mechanism of every method and the adverse effects and its limitations.

Low Z target switching to increase tumor endothelial cell dose enhancement during gold nanoparticle-aided radiation therapy.

Previous studies have introduced gold nanoparticles as vascular-disrupting agents during radiation therapy. Crucial to this concept is the low energy photon content of the therapy radiation beam. The authors introduce a new mode of delivery including a linear accelerator target that can toggle between low Z and high Z targets during beam delivery. In this study, the authors examine the potential increase in tumor blood vessel endothelial cell radiation dose enhancement with the low Z target. The authors use Monte Carlo methods to simulate delivery of three different clinical photon beams: (1) a 6 MV standard (Cu/W) beam, (2) a 6 MV flattening filter free (Cu/W), and (3) a 6 MV (carbon) beam. The photon energy spectra for each scenario are generated for depths in tissue-equivalent material: 2, 10, and 20 cm. The endothelial dose enhancement for each target and depth is calculated using a previously published analytic method. It is found that the carbon target increases the proportion of low energy (<150 keV) photons at 10 cm depth to 28% from 8% for the 6 MV standard (Cu/W) beam. This nearly quadrupling of the low energy photon content incident on a gold nanoparticle results in 7.7 times the endothelial dose enhancement as a 6 MV standard (Cu/W) beam at this depth. Increased surface dose from the low Z target can be mitigated by well-spaced beam arrangements. By using the fast-switching target, one can modulate the photon beam during delivery, producing a customized photon energy spectrum for each specific situation.

Design of an Yb-169 source optimized for gold nanoparticle-aided radiation therapy.

To find an optimum design of a new high-dose rate ytterbium (Yb)-169 brachytherapy source that would maximize the dose enhancement during gold nanoparticle-aided radiation therapy (GNRT), while meeting practical constraints for manufacturing a clinically relevant brachytherapy source. Four different Yb-169 source designs were considered in this investigation. The first three source models had a single encapsulation made of one of the following materials: aluminum, titanium, and stainless steel. The last source model adopted a dual encapsulation design with an inner aluminum capsule surrounding the Yb-core and an outer titanium capsule. Monte Carlo (MC) simulations using the Monte Carlo N-Particle code version 5 (MCNP5) were conducted initially to investigate the spectral changes caused by these four source designs and the associated variations in macroscopic dose enhancement across the tumor loaded with gold nanoparticles (GNPs) at 0.7% by weight. Subsequent MC simulations were performed using the EGSnrc and norec codes to determine the secondary electron spectra and microscopic dose enhancement as a result of irradiating the GNP-loaded tumor with the mcnp-calculated source spectra. Effects of the source filter design were apparent in the current MC results. The intensity-weighted average energy of the Yb-169 source varied from 108.9 to 122.9 keV, as the source encapsulation material changed from aluminum to stainless steel. Accordingly, the macroscopic dose enhancement calculated at 1 cm away from the source changed from 51.0% to 45.3%. The sources encapsulated by titanium and aluminum/titanium combination showed similar levels of dose enhancement, 49.3% at 1 cm, and average energies of 113.0 and 112.3 keV, respectively. While the secondary electron spectra due to the investigated source designs appeared to look similar in general, some differences were noted especially in the low energy region (<50 keV) of the spectra suggesting the dependence of the photoelectron yield on the atomic number of source filter material, consistent with the macroscopic dose enhancement results. A similar trend was also shown in the so-called microscopic dose enhancement factor, for example, resulting in the maximum values of 138 and 119 for the titanium- and the stainless steel-encapsulated Yb-169 sources, respectively. The current results consistently show that the dose enhancement achievable from the Yb-169 source is closely related with the atomic number (Z) of source encapsulation material. While the observed range of improvement in the dose enhancement may be considered moderate after factoring all uncertainties in the MC results, the current study provides a reasonable support for the encapsulation of the Yb-core with lower-Z materials than stainless steel, for GNRT applications. Overall, the titanium capsule design can be favored over the aluminum or dual aluminum/titanium capsule designs, due to its superior structural integrity and improved safety during manufacturing and clinical use.

WE‐A‐108‐03: Design of a New Yb‐169 Source Optimized for Gold Nanoparticle‐Aided Radiation Therapy

Purpose: To find an optimum design of a high‐dose rate Yb‐169 brachytherapy source for gold nanoparticle‐aided radiation therapy (GNRT). Previous studies suggested that the gamma‐ray energy spectrum of Yb‐169 could be almost ideal for a brachytherapy implementation of GNRT. The current study was aimed to design a new Yb‐169 source that would maximize dose enhancement during GNRT while meeting practical constraints for manufacturing a clinically‐relevant brachytherapy source. Methods: Monte Carlo simulations were conducted using the MCNP5 code to determine spectral changes caused by four different Yb‐169 source designs and associated variations in macroscopic dose enhancement across the tumor/ICRU tissue loaded with gold nanoparticles at 0.7% by weight. The first three source models had a single encapsulation made of aluminum, titanium, or stainless steel, while the last source model adopted a dual encapsulation design with an inner aluminum capsule and an outer titanium capsule. Results: The results showed spectral changes dependent on source design and their correlation with dose enhancement. The aluminum‐encapsulated source showed the lowest intensity‐weighted average energy of 108.9 keV, and the greatest dose enhancement of 51.0% at 1 cm away from the source center. The sources encapsulated by titanium and aluminum/titanium combination showed similar levels of dose enhancement, 49.2% and 49.3%, and average energies of 113.3 keV and 112.5 keV respectively. The source encapsulated with stainless steel exhibited the smallest dose enhancement, 43.8%, and the highest average energy of 126.6 keV. Conclusion: The current investigation suggests that the attainable macroscopic dose enhancement during GNRT with an Yb‐169 source can be further increased by encapsulating the Yb‐core with aluminum, titanium or aluminum/titanium combination, instead of stainless steel. Due to its structural integrity and improved safety during manufacturing and clinical uses, the dual encapsulation design would be preferred. Supported by DOD/PCRP grant W81XWH‐12‐1‐0198; DOD/PCRP grant W81XWH‐12‐1‐0198

DNA Damage Enhancement from Gold Nanoparticles for Clinical MV Photon Beams

In this study, we quantify the relative damage enhancement due to the presence of gold nanoparticles (GNP) in vitro in a clinical 6 MV beam for various delivery parameters and depths. It is expected that depths and delivery modes that produce a larger proportions of low-energy photons will have a larger effect on the cell samples containing GNP. HeLa cells with and without 50 nm GNP were irradiated at depths of 1.5, 5, 10, 15 and 20 cm. Conventional beams with square aperture sizes 5, 10 and 15 cm at isocenter, and flattening filter free (FFF) beams were used. Relative DNA damage enhancement with GNP was evaluated by γ-H2AX staining. Statistically significant increases in DNA damage with GNP, compared to the absence of GNP, were observed for all depths and delivery modes. Relative to the shallowest depth, damage enhancement was observed to increase as a function of increasing depth for all deliveries. For the conventional (open field) delivery, DNA damage enhancement with GNP was seen to increase as a function of field size. For FFF delivery, a substantial increase in enhancement was found relative to the conventional field delivery. The measured relative DNA damage enhancement validates the theoretically predicted trends as a function of depth and delivery mode for clinical MV photon beams. The results of this study open new possibilities for the clinical development of gold nanoparticle-aided radiation therapy.

Study of the Radiation Dose Enhancement at the Gold-Tissue Interface in Gold Nanoparticle-aided Radiation Therapy With Microdosimetry Technique

Study of the Radiation Dose Enhancement at the Gold-Tissue Interface in Gold Nanoparticle-aided Radiation Therapy With Microdosimetry Technique

TU-C-BRB-11: In Vitro Dose Enhancement from Gold Nanoparticles under Different Clinical MV Photon Beam Configurations

Purpose: To quantify the relative in vitro dose enhancement due to the presence of goldnanoparticles (GNPs) in a clinical 6 MV beam. It is expected that depths and delivery modes that produce larger proportions of low energy photons will have a larger effect on cell samples containing GNP. Methods: HeLa cells were combined with 50 nm GNPs at a concentration of 0 or 0.05 mg/ml. The cells were irradiated in clinical solid water at depths of 1.5, 5, 10, 15 and 20 cm (SAD setup). Conventional beams with square aperture sizes 5, 10 and 15 cm at isocenter, IMRT and flattening filter free (FFF) beams were used. DNA double strand breaks (DSBs) were evaluated by H2AX staining. Results: Statistically significant dose enhancement was observed for all depths and delivery modes. Dose enhancement ratios varied between 1.1 and 1.7. Relative to the shallowest depth, dose enhancement was observed to increase as a function of increasing depth for all deliveries. For the conventional (open field) delivery, dose enhancement was seen to increase as a function of field size. The IMRT delivery chosen for this study did not significantly increase the dose enhancement at each depth, but did in the aggregate. For FFF delivery, a substantial increase in gH2AX foci was found, relative to the conventional field delivery. Without GNP, no enhancement was observed as a function of depth, indicating that the enhancing effect with GNP is due to the change in energy spectrum under each delivery condition. Conclusions: The measured relative dose enhancement validates the theoretically predicted trends in dose enhancement as a function of depth and delivery mode for a clinical MV beam. The results of this study open new possibilities for the clinical development of goldnanoparticle aided radiation therapy.

Estimation of microscopic dose enhancement factor around gold nanoparticles by Monte Carlo calculations

An approach known as gold nanoparticle-aided radiation therapy (GNRT) is a recent development in radiation therapy which seeks to make a tumor more susceptible to radiation damage by modifying its photon interaction properties with an infusion of gold nanoparticles (GNPs). The purpose of this study was to quantify the energy deposition due to secondary electrons from GNPs on a nanometer scale and to calculate the corresponding microscopic dose enhancement factor around GNPs. The Monte Carlo code EGSnrc was modified to obtain the spectra of secondary electrons from atoms of gold approximating GNPs and molecules of water under photon irradiation of a tumor loaded with GNPs. Six different photon sources were used: 125I, 103Pd, 169Yb, 192Ir, 50 kVp, and 6 MV x rays. Treating the scored electron spectra as point sources within an infinite medium of water, the event-by-event Monte Carlo code NOREC was used to quantify the radial dose distribution, giving rise to gold/water electron dose point kernels and corresponding microscopic dose enhancement factors. These kernels were applied to a test case based on a scanning electron microscope image of a GNP distribution in tissue, enabling the determination of the microscopic dose enhancement at each dose point. For the lower energy sources 125I, 103Pd, 169Yb, and 50 kVp, the secondary electron fluence within a GNP-loaded tumor was increased by as much as two orders of magnitude, leading to two orders of magnitude increase in electron energy deposition over radial distances up to 10 microm. For the test case considered, the dose was enhanced by factors ranging from 2 to 20 within 5 microm of GNPs, and by 5% as far away as 30 microm. This study demonstrates a remarkable microscopic dose enhancement due to GNPs and low energy photon sources. By quantifying the microscopic dose enhancement factor for a given photon source as a function of distance from GNPs, it also enables the selection of either a passive or an active tumor targeting strategy using GNPs which will maximize the radiobiological benefit from GNRT.

Dependence of Dose Enhancement on Radial Distances during Gold Nanoparticle-aided Radiation Therapy with Low Energy Brachytherapy Sources

Dependence of Dose Enhancement on Radial Distances during Gold Nanoparticle-aided Radiation Therapy with Low Energy Brachytherapy Sources

The dosimetric feasibility of gold nanoparticle-aided radiation therapy (GNRT) via brachytherapy using low-energy gamma-/x-ray sources

The preferential accumulation of gold nanoparticles within tumors and the increased photoelectric absorption due to the high atomic number of gold cooperatively account for the possibility of significant tumor dose enhancement during gold nanoparticle-aided radiation therapy (GNRT). Among the many conceivable ways to implement GNRT clinically, a brachytherapy approach using low-energy gamma-/x-ray sources (i.e. Eavg < 100 keV) appears to be highly feasible and promising, because it may easily fulfill some of the technical and clinical requirements for GNRT. Therefore, the current study investigated the dosimetric feasibility of implementing GNRT using the following sources: 125I, 50 kVp and 169Yb. Specifically, Monte Carlo (MC) calculations were performed to determine the macroscopic dose enhancement factors (MDEF), defined as the ratio of the average dose in the tumor region with and without the presence of gold nanoparticles during the irradiation of the tumor, and the photo/Auger electron spectra within a tumor loaded with gold nanoparticles. The current study suggests that a significant tumor dose enhancement (e.g. >40%) could be achievable using 125I, 50 kVp and 169Yb sources and gold nanoparticles. When calculated at 1.0 cm from the center of the source within a tumor loaded with 18 mg Au g−1, macroscopic dose enhancement was 116, 92 and 108% for 125I, 50 kVp and 169Yb, respectively. For a tumor loaded with 7 mg Au g−1, it was 68, 57 and 44% at 1 cm from the center of the source for 125I, 50 kVp and 169Yb, respectively. The estimated MDEF values for 169Yb were remarkably larger than those for 192Ir, on average by up to about 70 and 30%, for 18 mg Au and 7 mg Au cases, respectively. The current MC study also shows a remarkable change in the photoelectron fluence and spectrum (e.g. more than two orders of magnitude) and a significant production (e.g. comparable to the number of photoelectrons) of the Auger electrons within the tumor region due to the presence of gold nanoparticles during low-energy gamma-/x-ray irradiation. The radiation sources considered in this study are currently available and tumor gold concentration levels considered in this investigation are deemed achievable. Therefore, the current results strongly suggest that GNRT can be successfully implemented via brachytherapy with low energy gamma-/x-ray sources, especially with a high dose rate 169Yb source.

TH-D-210A-04: Monte Carlo Calculations of Microscopic Dose Enhancement Factor for Gold Nanoparticle-Aided Radiation Therapy

Purpose: To quantify the energy deposition due to photoelectrons from goldnanoparticles on a micrometer scale and to calculate the corresponding microscopic dose enhancement factor during GoldNanoparticle‐AidedRadiation Therapy (GNRT). Method and Materials: The Monte Carlo code EGSnrc was modified to obtain the spectra of secondary electrons from atoms of gold and molecules of water under photon irradiation of a tumor infused with 0.7 wt. % gold. Six different photon sources were used: 125I, 103Pd, 169Yb, 192Ir, 50kVp, and 6MV x‐rays. Treating the scored electron spectra as point sources within an infinite medium of water, the event‐by‐event Monte Carlo code NOREC was used to quantify the radial dose distribution, giving rise to gold and water electron dose point kernels. These kernels were applied to a scanning electron microscope(SEM)image of a goldnanoparticle distribution in tissue. Treating each pixel in the image as a point source of gold or water emitting secondary electrons, the dose at each point was calculated, enabling the determination of the microscopic dose enhancement at each point. Results: For the lower energy sources 125I, 103Pd, 169Yb, and 50 kVp, the secondary electron fluence was increased by as much as two orders of magnitude, leading to a one‐to‐two order of magnitude increase in the electron dose point kernel over radial distances up to 50 μm. The dose was enhanced by 100% within 5 μm of the nanoparticles, and by 5% as far away as 30 μm. Conclusion: This study demonstrates a remarkable microscopic dose enhancement due to goldnanoparticles and low energy photon sources. Given that the dose enhancement exceeds 100% within very short (5 μm) distances from the nanoparticles, the maximum radiobiological benefit may be derived from active targeting strategies that concentrate nanoparticles in close proximity to the cancer cell and/or its nucleus.

SU‐GG‐J‐139: On the Clinical Implementation of Gold Nanoparticle‐Aided Radiation Therapy (GNRT)

Purpose: To present possible strategies for the clinical implementation of gold nanoparticle‐aided radiation therapy (GNRT). Method and Materials: GNRT is an emerging treatment modality currently under development. GNRT would provide a way to substantially escalate the tumor dose far beyond the current limit while maintaining the normal tissue dose at the levels comparable to conventional radiation therapy. The current study investigated possible strategies for clinical implementation of GNRT by surveying existing in‐vivo data and performing Monte Carlo (MC) calculations for the cases mimicking typical clinical situations. The cases included in this study were a brachytherapy case using Yb‐169 source and an external beam radiation therapy (EBRT) case using low energy‐enhanced megavoltage photon beams (e.g., 4 MV and 2 MV) that can be generated by a slight modification of a conventional design of linear accelerators. Results: The MC calculations suggest the macroscopic dose enhancement factor (MDEF) within the tumor region could be 42 and 200%, for the gold concentration levels of 7 and 18 mg Au/ g tumor, respectively, with Yb‐169 source. The current results also suggest the macroscopic dose enhancement ranging 10 to 40% could be achievable across the tumor volume with low energy‐enhanced megavoltage photon beams at a realistic tumor gold concentration (e.g., between 7 and 30 mg Au/g tumor). Besides, the current investigation indicates the dose distributions due to low energy‐enhanced megavoltage photon beams could be created comparable to those due to conventional megavoltage beams, while producing the suggested level of tumor dose enhancement. Conclusion: According to the current study, GNRT appears to be very feasible via a brachytherapy apparoch using Yb‐169 source. GNRT also appears to be feasible for EBRT with low energy‐enhanced megavoltage photon beams. The tumor dose under these implementation scenarios may be enhanced further with an active targeting of tumor cells with gold nanoparticles.

SU-GG-J-129: Monte Carlo Calculations of Secondary Electron Spectra for Various Mixtures of Gold and Water Mimicking Tumors Loaded with Gold Nanoparticles

Purpose: To determine the change in secondary electronspectrum due to goldnanoparticles present in a tumor under a treatment scenario of goldnanoparticle‐aidedradiation therapy (GNRT). Method and Materials: The Monte Carlo code, EGSnrc, was modified to obtain the spectrum of secondary electrons. Simulations were performed with a water phantom containing a small gold‐loaded region at various gold concentration levels (0.1–3%). The atom of origin and energy of each Compton and photoelectron was tracked, yielding the secondary electronspectrum of gold and water for each simulation. Results: The presence of gold caused a significant increase in the number of photoelectrons generated. With 0.1%, 1%, and 3% gold in the region of interest, the total energy transferred to electrons through the photoelectric and Compton processes increased by 1.5%, 15%, and 49%, respectively. Conclusion: The spectra generated in this study are helpful for a better understanding of the physical mechanisms responsible for dose enhancement within a gold‐loaded tumor during GNRT. They can also be used as inputs for detailed history Monte Carlo calculations to perform a nanodosimetric estimation of tumordose enhancement in the vicinity of a goldnanoparticle.

SU‐GG‐J‐67: Detection of Gold Fluorescence X‐Rays for the In‐Vivo Quantification of Gold Concentration During Gold Nanoparticle‐Aided Radiation Therapy (GNRT)

Purpose: To determine the concentration of gold (Au) nanoparticles presented within the tumor during in vivo demonstration of tumor dose enhancement by detecting gold fluorescence x‐rays. Method and Materials: Gold nanoparticle solution of 1% by weight in saline was prepared using commercially available gold nanoparticles with 1.9 nm core diameter. A cylindrical sample container (2.5 cm in diameter and 5.0 cm in height) was irradiated with 110 kVp and 200 mA x‐rays from conventional radiotherapy simulator for 40 seconds with 1 cm × 1 cm x‐ray beam at 85 cm source‐to‐surface distance (SSD) and spectrum was obtained using either Si‐PIN or CdTe photodiode detector using a container‐to‐detector geometry to minimize unwanted photons entering the detector. Results: The spectrum collected using the Si detector successfully captured the Au Lα and Lβ fluorescence lines at 9.7 and 11.4 keV, respectively, well above the background. Au K lines could not be measured with Si‐PIN photodiode due to Si‐PIN detection inefficiency above 60 keV. To capture the Au K lines, CdTe photodiode detector was employed which has high detection efficiency for energy range of Au K lines. The spectrum collected using CdTe detector clearly showed the Au Kα2, Kα1, and Kβ lines corresponding to energies of 67.0, 68.8, and 77.9 keV, respectively. Conclusion: The magnitude of obtained Kα fluorescence signal (i.e. greater than 50% above all background scattering) is very encouraging considering the tested gold concentration. With more sophisticated geometry to minimize scattered photons reaching the detector, Au fluorescence output from K lines can be used to measure even lower concentrations of gold nanoparticles. Fluorescence output as a function of Au concentration can be developed to accurately measure gold nanoparticle concentration.

Dosimetric Feasibility of Gold Nanoparticle-Aided Radiation Therapy (GNRT) Using a Yb-169 Source

Gold nanoparticle-aided radiation therapy (GNRT) is an emerging treatment modality currently under development, based on the following observations: a) high tumor specificity of gold nanoparticles due to passive extravasation; b) significant tumor dose enhancement during x-ray irradiation as a result of increased photoelectric absorption due to high atomic number (Z) of gold. GNRT may provide new options to deal with a number of clinical challenges such as a dose escalation beyond the current limit, a more effective management of radio-resistant tumors, etc.

SU-FF-T-292: Microscopic Estimation of Tumor Dose Enhancement During Gold Nanoparticle-Aided Radiation Therapy (GNRT) Using Diagnostic Energy Range X-Rays

Purpose: To estimate microscopic tumordose enhancement due to goldnanoparticles during goldnanoparticle‐aidedradiation therapy (GNRT). Method and Materials: GNRT is an emerging treatment modality currently under development, based on the following observations: a) high tumor specificity of goldnanoparticles due to passive extravasation; b) significant tumordose enhancement during x‐ray irradiation as a result of increased photoelectric absorption due to high atomic number (Z) of gold. A previous Monte Carlo study provided some quantitative estimation of macroscopic dose enhancement (i.e., the average dose enhancement over the entire tumor volume) for a number of GNRT scenarios, which is useful to understand potential therapeutic outcome, in terms of a conventional dose response scheme. On the other hand, the magnitude of physical dose enhancement at the cellular level is expected to be drastically different from that averaged over the tumor volume. Therefore, the current study attempted to estimate microscopic tumordose enhancement for a clinically feasible GNRT scenario using diagnostic energy range x‐rays. Specifically, after obtaining secondary electron spectra due to interactions between 140 kV x‐rays and goldnanoparticles, detailed history Monte Carlo calculations were performed at a nanometer scale to estimate the energy deposition by secondary electrons originated from goldnanoparticles.Results: The current results suggest that the microscopic dose enhancement up to a factor of 8 could be possible within 20 microns from a single goldnanoparticle. The results also show that the magnitude of microscopic dose enhancement is a function of the distance from the site of a goldnanoparticle.Conclusion: A drastic tumordose enhancement (i.e., > 100%) at the cellular level could be achievable during GNRT using diagnostic energy range x‐rays. However, an actual radiobiological outcome would depend on a number of factors such as the size, amount, and distribution of goldnanoparticles within the tumor.

SU‐FF‐T‐324: Modifications of Megavoltage Photon Beams for Gold Nanoparticle‐Aided Radiation Therapy (GNRT): A Monte Carlo Study

Purpose: To produce megavoltage photon beams capable of achieving clinically significant (&gt; 10%) macroscopic tumor dose enhancement during gold nanoparticle‐aided radiation therapy (GNRT). Method and Materials: GNRT is an emerging treatment modality currently under development, based on the following observations: a) high tumor specificity of gold nanoparticles due to passive extravasation; b) significant tumor dose enhancement during x‐ray irradiation as a result of increased photoelectric absorption due to high atomic number (Z) of gold. A previous Monte Carlo study found that no meaningful tumor dose enhancement would occur during GNRT with typical megavoltage photon beams, even after the removal of the flattening filter from linear accelerators. Therefore, the current Monte Carlo study investigated a number of ways to further increase the amount of low energy photons in the beam and consequently to achieve clinically significant tumor dose enhancement with photon beams in megavoltage range. Specifically, the macroscopic tumor dose enhancement under the identical geometry was calculated using the BEAMnrc/DOSXYZnrc code as the following conditions changed: the energy of electron pencil beam incident on the target, the target thickness, and the target material. Results: The current results showed that the macroscopic dose enhancement up to 40 and 18% across the tumor volume could be achievable with unflattened 2 and 4 MV photon beams, respectively, at a reasonable gold concentration of 3% within the tumor, after the proposed changes in target thickness and material. These beams were found capable of producing clinically acceptable treatment plans for GNRT, in spite of their softer photon energy spectra and larger buildup doses, compared to conventional megavoltage beams at the same nominal photon energies. Conclusion: Clinically significant tumor dose enhancement could be achievable during GNRT with megavoltage photon beams, provided that the proposed modifications to linear accelerators are made.