Gold nanoparticle (GNP) enhanced radiosensitization was studied across three tumour cells lines that vary in radiosensitivity for a 2.5 MV photon beam. The intrinsic sensitivity of the cell lines is studied for the effects of GNPs. Three cell lines which exhibit differences in radiation response: prostate adenocarcinoma (PC-3), breast adenocarcinoma (MDA-MB-231), and cervical adenocarcinoma (HeLa) were used to determine thein vitrodose enhancement effects of GNPs combined with a 2.5 MV photon beam. Cells were incubated with 20 μg ml-1GNPs for 24 h, and any extracellular GNPs were washed out prior to each assay. The cellular uptake of GNPs was assessed with inductively coupled plasma optical emission spectroscopy (ICP-OES). Clonogenic assays were conducted to assess cell viability after irradiation. The biological damage was assessed through DNA damage using terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL). The production of reactive oxygen species (ROS) was assessed using CellRox assays. The enhancement factor when cells were irradiated in the presence of GNPs with 2.5 MV was 1.35 ± 0.46 for HeLa, 1.35 ± 0.11 for MDA-MB-231, and 0.99 ± 0.08 for PC-3 cells. On average, the level of DNA damage increased in MDA-MB-231 and HeLa cells when irradiated with 2.5 MV in the presence of GNPs. Increase in the ROS levels were detected in all cell lines when irradiated in the presence of GNPs. The enhancement effects with GNPs combined with a 2.5 MV photon beam were dependent on the cell line. The enhancement factor for HeLa and MDA-MB-231 supports further investigation of intermediate photon-energy beams in combination with GNPs. The combination of using a conventionally lower energy megavoltage beam with gold nanoparticles may become applicable in the clinical setting due to reduced skin dose and enhanced secondary electron production.

Objective. This study investigates the feasibility of using a clinically relevant lower energy 2.5 megavoltage (MV) photon beam in combination with gold nanoparticles (GNPs).Approach.Pancreatic cancer cell line, BxPC-3 impregnated with GNPs were exposedin vitroto 2.5 MV photon beam and compared with orthovoltage 225 kV and clinical 6 MV photon beam. Bare, 50 nm diameter, spherical GNPs were introduced in the cell culture 24 h prior to irradiation at a concentration of either 10μg ml-1or 50μg ml-1. GNP uptake was determined using inductively coupled plasma optical emission spectroscopy. The cells were irradiated with doses between 0 Gy to 8 Gy. Cell survival curves were obtained via clonogenic assay using immediate or delayed plating (24 h) methods 12 d after irradiation. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to evaluate DNA damage at two time points post irradiation, immediate and 24 h for 1 Gy and 6 Gy.Main results. The enhancement factor (EF) in BxPC-3 cells was greatest for cells incubated with 50μg ml-1of GNPs analyzed immediately post irradiation. Cells irradiated with 225 kV showed greatest EF (1.57 ± 0.15), followed by 2.5 MV (1.51 ± 0.04). The lowest EF was seen for 6 MV, immediate plating (1.10 ± 0.04). A significant increase in the number of DNA double strand breaks (DSB) was observed in cells incubated with 50μg ml-1of GNPs irradiated at 6 Gy with 225 kV and 2.5 MV. There was no significant increase in DSBs for the cells irradiated with 6 MV.Significance.These results suggest that the 2.5 MV could be a compromise between an orthovoltage energy beam and a clinical 6 MV beam, showing comparable reduction in cell survival to the 225 kV beam. Future GNP radiation enhancement research may focus on intermediate energy beams.

Radionuclides decaying by electron capture or internal transition produce a large number of Auger electrons in a cascade that follows their radioactive decay. A shortlist of the most potent Auger electron-emitters has appeared in the literature including 103m Rh, 103 Pd, 111 In, 119 Sb, 123 I, 125 I, 165 Er, and 197 Hg. Among them, 119 Sb has been identified as the most potent for targeting micrometastases, yielding several tens of Auger electrons per decay with energies from a few eV up to 30 keV. In this paper, we recalculate Auger, Coster-Kronig, and super Coster-Kronig yields and transition probabilities as subshell-normalized relative transition probabilities and develop a new method to create radionuclide sources in TOPAS Monte Carlo, the code for which has been made publicly available. We then apply our method to encode the Auger electron spectra of 119 Sb from MIRD RADTABS and EADL into TOPAS and calculate the absorbed dose to water volumes of radius 10 nm up to 10 μm, finding that the averaged MIRD Auger electron spectrum underestimates the absorbed dose by a factor of 20 to 50 on this scale. We show that this result is not isolated to 119 Sb and conclude that either the cascaded MIRD or EADL spectrum should be used for accurate microscale dosimetry. We compare with results obtained using the built-in Geant4 Atomic Relaxation for 119 Sb in TOPAS and find an unexpected continuum of low-energy electrons but no excess absorbed dose relative to either MIRD or EADL. We show that 119 Sb does not produce more absorbed dose in microscale volumes than 103m Rh, 103 Pd, 111 In, 123 I, 125 I, 165 Er, or 197 Hg, warranting future microdosimetry calculations of RBE and DNA damage to understand whether 119 Sb is the most potent Auger electron-emitter, as claimed in the literature.

Objective. This study simulated the potential of gold nanoparticles (GNPs) to improve the effectiveness of radiation therapy in pancreatic cancer cases. The purpose of this study was to assess the impact of GNPs on tumor control probability (TCP) and normal tissue complication probability (NTCP) in pancreatic cancer cases undergoing radiation therapy. The work aimed to compare treatment plans generated with a novel 2.5 MV beam using GNPs to conventional 6 MV plans and evaluate the dose-volume histogram (DVH), TCP, and NTCP. Approach. Treatment planning for five pancreatic computed tomography (CT) images was performed using the open-source MATLAB-based treatment planning program matRad. MATLAB codes were developed to calculate the relative biological effectiveness (RBE) of GNPs and apply the corresponding dose and RBE values to each voxel. TCP and NTCP were calculated based on the applied RBE values. Main results. Adding GNPs to the 2.5 MV treatment plan resulted in a significant increase in TCP, from around 59% to 93.5%, indicating that the inclusion of GNPs improved the effectiveness of the radiation treatment. The range in NTCP without GNPs was relatively larger compared to that with GNPs. Significance. The results indicated that the addition of GNPs to a 2.5 MV plan can increase TCP while maintaining a relatively low NTCP value (<1%). The use of GNPs may also reduce NTCP values by decreasing the dose to normal tissues while maintaining the same prescribed dose to the tumor. Hence, the addition of GNPs can improve the balance between TCP and NTCP.

Dose falls-off faster than the inverse square law (ISL) for orthovoltage beams with closed-ended applicators. This work investigates the discrepancy for 30 cm FSD applicators. When using the ISL alone, the maximum dosimetric error would be 3% and 5% at 10 mm and 20 mm from the applicator, respectively, and increases with larger distances. The effective source position was found to be 22.5 cm and reduces the dosimetric error to less than 1.6% for distances less than 20 mm.

Radiosurgery and stereotactic radiotherapy have established themselves as precise and accurate areas of radiation oncology for the treatment of brain and extracranial lesions. Along with the evolution of other methods of radiotherapy, this type of treatment has been associated with significant advances in terms of a variety of modalities and techniques to improve the accuracy and efficacy of treatment. This paper provides a comprehensive overview of the progress in stereotactic radiosurgery (SRS) over several decades, and includes a review of various articles and research papers, commencing with the emergence of stereotactic techniques in radiotherapy. Key clinical aspects of SRS, such as fixation methods, radiobiology considerations, quality assurance practices, and treatment planning strategies, are presented. In addition, the review highlights the technological advancements in treatment modalities, encompassing the transition from cobalt-based systems to linear accelerator-based modalities. By addressing these topics, this study aims to offer insights into the advancements that have shaped the field of SRS, that have ultimately enhanced the accuracy and effectiveness of treatment.

AbstractPurposeThe shallow depth of maximum dose and higher dose fall‐off gradient of a 2.5 MV beam along the central axis that is available for imaging on linear accelerators is investigated for treatment of shallow tumors and sparing the organs at risk (OARs) beyond it. In addition, the 2.5 MV beam has an energy bridging the gap between kilo‐voltage (kV) and mega‐voltage (MV) beams for applications of dose enhancement with high atomic number (Z) nanoparticles.MethodsWe have commissioned and utilized a MATLAB‐based, open‐source treatment planning software (TPS), matRad, for intensity‐modulated radiation therapy (IMRT) dose calculations. Treatment plans for prostate, liver, and head and neck (H&N), nasal cavity, two orbit cases, and glioblastoma multiforme (GBM) were performed and compared to a conventional 6 MV beam. Additional Monte Carlo calculations were also used for benchmarking the central axis dose.ResultsBoth beams had similar planning target volume (PTV) dose coverage for all cases. However, the 2.5 MV beam deposited 6%–19% less integral doses to the nasal cavity, orbit, and GBM cases than 6 MV photons. The mean dose to the heart in the liver plan was 10.5% lower for 2.5 MV beam. The difference between the doses to OARs of H&N for two beams was under 3%. Brain mean dose, brainstem, and optic chiasm max doses were, respectively, 7.5%–14.9%, 2.2%–8.1%, and 2.5%–19.0% lower for the 2.5 MV beam in the nasal cavity, orbit, and GBM plans.ConclusionsThis study demonstrates that the 2.5 MV beam can produce clinically relevant treatment plans, motivating future efforts for design of single‐energy LINACs. Such a machine will be capable of producing beams at this energy beneficial for low‐ and middle‐income countries, and investigations on dose enhancement from high‐Z nanoparticles.

Development of portable X-ray fluorescence devices has made it easier to quickly assess trace elements such as zinc in human tissue. A TOPAS Monte Carlo code was used to investigate the use of a portable X-ray fluorescence system for detecting zinc in nail clippings. The obtained energy spectra from different nail thicknesses were analyzed and three different normalization techniques (coherent, Compton, and entire spectrum) were introduced. The simulation results suggested that coherent normalization can be a particularly robust normalization procedure.

The air kerma rate constant is important for estimating radiation dose and shielding calculations to ensure radiation exposure is as low as reasonably achievable (ALARA). Currently, there are significant deviations in this constant reported for 241Am by various institutions. Therefore, through first principle calculations and simulation, we investigate the air kerma rate constant for 241Am based on photon energies and emission probabilities reported in literature.

Purpose A multi‐scale investigation of the biological properties of gadolinium neutron capture (GdNC) therapy with applications in particle therapy is conducted using the TOPAS Monte Carlo (MC) simulation code. The simulation results are used to quantify the amount of gadolinium dose enhancement produced as a result of the secondary neutron production from proton therapy scaled by measured data. Materials and methods MC modeling was performed using the radiobiology extension TOol for PArticle Simulation TOPAS‐nBio MC simulation code to study the radiobiological effects produced from GdNC on a segment of DNA, a spherical cellular model, and from the modeling of previous experimental measurements. The average RBE values were calculated from two methods, microdosimetric kinematic (MK) and biological weighting r(y) within a 2 nm DNA segment for GdNC. The single‐strand breaks (SSBs) and double‐strand breaks (DSBs) were calculated from within the nucleus of a 20 µm diameter, spherical cell model. From a previous experimental proton therapy measurement using a spread‐out Bragg peak (SOBP) of 4.5–9.5 cm and a delivered absorbed dose of 10.4 Gy, the amount of Gd neutron captures was calculated and used to quantify the amount of GdNC absolute dose from particle therapy. Results The average RBE from microdosimetric kinematic and biological weighting was 1.35, and 1.70 for a 10% cell survival on HSG cell‐line and weighting function data from early intestinal tolerance of mice. From a central isotropic GdNC source, the energy deposition is found to decrease from roughly 2.7 eV per capture down to approximately 0.01 eV per capture, a drop of two orders of magnitude within 50 nm. This result suggests that Gd needs to be close to the DNA (within 10–20 nm) in order for neutron capture to induce a significant dose enhancement due to the short‐range electrons emitted after Gd neutron capture. Within a spherical cell model, the SSBs, and DSBs were determined to be 39 and 1.5 per neutron capture, respectively. From the total neutron captures produced from an experimental proton therapy measurement on a 3000 PPM Gd solution, an insignificant absolute Gd dose enhancement was quantified to be 5.4 × 10 −6 Gy per Gy of administered proton dose. Conclusion From this study and literature review, the production of secondary thermal neutrons from proton therapy is determined to be a limiting factor and unlikely to produce a clinically useful dose enhancement for secondary neutron capture therapy. Moreover, alternative neutron sources, such as, a compact deuterium‐tritium (D‐T) neutron generator, a “high yield” deuterium‐deuterium (D‐D) generator, or an industrial strength (100 mg) 252 Cf source were investigated, with the 252 Cf source the most likely to be capable of producing enough neutrons for 1 Gy of localized GdNC absolute dose within a reasonable treatment time.

Purpose: The purpose of this work was to present a new single-arc mixed photon (6&18MV) VMAT (SAMP) optimization framework that concurrently optimizes for two photon energies with corresponding partial arc lengths. & nbsp; Methods and materials: Owing to simultaneous optimization of energy dependent intensity maps and corresponding arc locations, the proposed model poses nonlinearity. Unique relaxation constraints based on McCormick approximations were introduced for linearization. Energy dependent intensity maps were then decomposed to generate apertures. Feasibility of the proposed framework was tested on a sample of ten prostate cancer cases with lateral separation ranging from 34 cm (case no.1) to 52 cm (case no.6). The SAMP plans were compared against single energy (6MV) VMAT (SE) plans through dose volume histograms (DVHs) and radiobiological parameters including normal tissue complication probability (NTCP) and equivalent uniform dose (EUD). Results: The contribution of higher energy photon beam optimized by the algorithm demonstrated an increase for cases with a lateral separation >40 cm. SAMP?VMAT notably improved bladder and rectum sparing in large size cases. Compared to single energy, SAMP?VMAT plans reduced bladder and rectum NTCP in cases with large lateral separation. With the exception of one case, SAMP?VMAT either improved or maintained femoral heads compared to SE?VMAT. SAMP?VMAT reduced the nontarget tissue integral dose in all ten cases. Conclusions: A single-arc VMAT optimization framework comprising mixed photon energy partial arcs was presented. Overall results underline the feasibility and potential of the proposed approach for improving OAR sparing in large size patients without compromising the target homogeneity and coverage.

The purpose of this work was to investigate the use of a commercial cadmium-telluride detector as an absolute thermal neutron measurement device on a proton therapy unit. Experimental measurements were performed on water phantoms using a 25 mm(2), 1 mm thick uncollimated CdTe spectrometer. The detector was shielded using sheets of borated polyethylene minimizing the measured direct neutron spectrum from the treatment nozzle. For each measurement a significant 95.9 keV prompt gamma-ray peak resulting from Cd-113 thermal neutron capture within the CdTe detector was observed. For comparison, and to identify relevant trends, all setups were simulated within the Monte Carlo code MCNP6. For a dose of 21.0 Gy to a 100 mL water phantom, 0-5 cm spread out Bragg peak (SOBP), 7760 +/- 299 counts (corrected for dead-time) were measured at the detector location 10 cm from the water surface and perpendicular to the proton beam, which corresponds to an absolute fluence of 1.5 x 10(6) thermal neutrons/cm(2). The delivery of 8.3 Gy, 1.5 to 6.5 SOBP within a water tank phantom resulted in 2522 +/- 233 counts or 4.9 x 10(5) thermal neutrons/cm(2) with the detector located 5 cm away from the surface of the water tank phantom. Using MCNP6, the simulated thermal neutron fluence was determined to be within the same order of magnitude and within a factor of 3 for all configurations. This research demonstrates the first use of cadmium-telluride (CdTe) as an absolute slow neutron detector for the application of proton therapy and neutron dosimetry.

Proton neutron gamma-x detection (PNGXD) is a novel imaging concept being investigated for tumor localization during proton therapy that uses secondary neutron interactions with a gadolinium contrast agent (GDCA) to produce characteristic photons within the 40-200 keV energy region. The purpose of this study is to experimentally investigate the feasibility of implementing this procedure by performing experimental measurements on a passive double scattering proton treatment unit. Five experimental measurements were performed with varying concentrations and irradiation conditions. Photon spectra were measured with a 25 mm2, 1 mm thick uncollimated X-123 CdTe spectrometer. For a 10.4 Gy administration on a 100 ml volume phantom with 10 mg g-1 Gd solution placed in a water phantom, 1129  ±  184 K-shell Gd counts were detected. For an administered dose of 21 Gy and the same Gd solution measured in air, resulted in 3296  ±  256 counts. A total of 1094  ±  171, 421  ±  150 and 23  ±  141 K-shell Gd counts were measured for Gd concentrations of 10 mg g-1, 1 mg g-1 and 0 mg g-1 for 7 Gy dose in air. The signal to noise ratio for these five measurements were: 7, 15, 6, 3, and 0.2, respectively. The spectrum contained 43 keV K α and 49 keV K β peaks, however a small amount of 79.5 and 181.9 keV prompt gamma rays were detected from gadolinium neutron capture. This discrepancy is due to a drop in the intrinsic detection efficiency of the CdTe spectrometer over this energy range. The measurements were compared with Monte-Carlo simulation to determine the contributions of Gd neutron capture from internal and external neutrons on a passive scattering proton therapy unit and to investigate the discrepancy in detected characteristic x-rays versus prompt gamma rays.

This study investigates the photon production from thermal neutron capture in a gadolinium (Gd) infused tumor as a result of secondary neutrons from particle therapy. Gadolinium contrast agents used in MRI are distributed within the tumor volume and can act as neutron capture agents. As a result of particle therapy, secondary neutrons are produced and absorbed by Gd in the tumor providing potential enhanced localized dose in addition to a signature photon spectrum that can be used to produce an image of the Gd enriched tumor. To investigate this imaging application, Monte Carlo (MC) simulations were performed for 10 different particles using a 5–10 cm spread out-Bragg peak (SOBP) centered on an 8 cm 3 , 3 mg/g Gd infused tumor. For a proton beam, 1.9 × 10 6 neutron captures per RBE weighted Gray Equivalent dose (GyE) occurred within the Gd tumor region. Antiprotons ( P̅ ), negative pions (− π), and helium (He) ion beams resulted in 10, 17 and 1.3 times larger Gd neutron captures per GyE than protons, respectively. Therefore, the characteristic photon based spectroscopic imaging and secondary Gd dose enhancement could be viable and likely beneficial for these three particles.

Objectives: Lanthanum (La) retention in bone has been shown to occur in individuals who are orally administered lanthanum carbonate (LaC), a drug to treat hyperphosphatemia. The breakdown of LaC in the gastrointestinal tract into La3+ and carbonate ions results in residual quantities of La being deposited in bone. We previously reported on a non-invasive x-ray fluorescence (XRF) system that was developed to quantify bone La concentrations and applied it to a series of excised cadaver tibiae. However, given interpatient variability in bone shape and size, differential signal attenuation that occurs in bone and tissue, patient movement and overlying tissue thickness at the measurement site, quantifying bone La concentrations during in vivo measurements in live subjects needs to be investigated further along with the radiation dose associated with the measurement. Approach: Coherent normalization was investigated as a function of overlying tissue thickness, source-subject distance and bone radius through Monte Carlo simulation and experimental work. This was accomplished by observing the ratio of the net La K x-ray peak area to the coherently scattered peak area at 59.5 keV. In addition, the dose delivered during a 2000 s measurement was determined using radiochromic film. Main results: The coherent normalization of the La x-ray signal was shown to be independent of overlying tissue thickness, source-subject movement and bone radius, which indicates that this normalization procedure can correct for these factors. The equivalent skin dose and effective dose were 18.0 mSv and 3.2 μSv, respectively for a five-year-old. Significance: While coherent normalization for the bone lead (Pb) and bone gadolinium (Gd) systems has been shown to be successful, we also report that this normalization procedure can correct for these interpatient variabilities in the in vivo241Am-La K XRF system.