A quantitative assessment of Geant4 for predicting the yield and distribution of positron-emitting fragments in ion beam therapy.

PURPOSE: To compare the accuracy with which different hadronic inelastic physics models across ten Geant4 Monte Carlo simulation toolkit versions can predict positron-emitting fragments produced along the beam path during carbon and oxygen ion therapy. Materials and Methods: Phantoms of polyethylene, gelatin or poly(methyl methacrylate) were irradiated with monoenergetic carbon and oxygen ion beams. Post-irradiation, 4D PET images were acquired and parent11C,10C and15O radionuclides contributions in each voxel were determined from the extracted time activity curves. Next, the experimental configurations were simulated in Geant4 Monte Carlo versions 10.0 to 11.1, with three different fragmentation models - binary ion cascade (BIC), quantum molecular dynamics (QMD) and the Liege intranuclear cascade (INCL++) - 30 model-version combinations. Total positron annihilation and parent isotope production yields predicted by each simulation were compared between simulations and experiments using normalised mean squared error and Pearson cross-correlation coefficient. Finally, we compared the depth of maximum positron annihilation yield and the distal point at which positron yield decreases to 50% of peak between each model and the experimental results. Results: Performance varied considerably across versions and models, with no one version/model combination providing the best prediction of all positron-emitting fragments in all evaluated target materials and irradiation conidiations. BIC in Geant4 10.2 provided the best overall agreement with experimental results in the largest number of test cases. QMD consistently provided the best estimates of both the depth of peak positron yield (10.4 and 10.6) and the distal 50%-of-peak point (10.2), while BIC also performed well and INCL generally performed the worst across most Geant4 versions. Conclusions: Best spatial prediction of annihilation yield and positron-emitting fragment production during carbon and oxygen ion therapy was found to be 10.2.p03 with BIC or QMD. These version/model combinations are recommended for future heavy ion therapy research.

Neutron Capture Enhances Dose and Reduces Cancer Cell Viability in and out of Beam During Helium and Carbon Ion Therapy.

PURPOSE: Neutron capture enhanced particle therapy (NCEPT) is a proposed augmentation of charged particle therapy that exploits thermal neutrons generated internally, within the treatment volume via nuclear fragmentation, to deliver a biochemically targeted radiation dose to cancer cells. This work is the first experimental demonstration of NCEPT, performed using both carbon and helium ion beams with 2 different targeted neutron capture agents (NCAs). METHODS AND MATERIALS: Human glioblastoma cells (T98G) were irradiated by carbon and helium ion beams in the presence of NCAs [10B]-BPA and [157Gd]-DOTA-TPP. Cells were positioned within a polymethyl methacrylate phantom either laterally adjacent to or within a 100 × 100 × 60 mm spread out Bragg peak (SOBP). The effect of NCAs and location relative to the SOBP on the cells was measured by cell growth and survival assays in 6 independent experiments. Neutron fluence within the phantom was characterized by quantifying the neutron activation of gold foil. RESULTS: Cells placed inside the treatment volume reached 10% survival by 2 Gy of carbon or 2 to 3 Gy of helium in the presence of NCAs compared with 5 Gy of carbon and 7 Gy of helium with no NCA. Cells placed adjacent to the treatment volume showed a dose-dependent decrease in cell growth when treated with NCAs, reaching 10% survival by 6 Gy of carbon or helium (to the treatment volume), compared with no detectable effect on cells without NCA. The mean thermal neutron fluence at the center of the SOBP was approximately 2.2 × 109 n/cm2/Gy (relative biological effectiveness) for the carbon beam and 5.8 × 109 n/cm2/Gy (relative biological effectiveness) for the helium beam and gradually decreased in all directions. CONCLUSIONS: The addition of NCAs to cancer cells during carbon and helium beam irradiation has a measurable effect on cell survival and growth in vitro. Through the capture of internally generated neutrons, NCEPT introduces the concept of a biochemically targeted radiation dose to charged particle therapy. NCEPT enables the established pharmaceuticals and concepts of neutron capture therapy to be applied to a wider range of deeply situated and diffuse tumors, by targeting this dose to microinfiltrates and cells outside of defined treatment regions. These results also demonstrate the potential for NCEPT to provide an increased dose to tumor tissue within the treatment volume, with a reduction in radiation doses to off-target tissue.

First experimental demonstration of real-time neutron capture discrimination in helium and carbon ion therapy.

This work provides the first experimental proof of an increased neutron capture photon signal following the introduction of boron to a PMMA phantom during helium and carbon ion therapies in Neutron Capture Enhanced Particle Therapy (NCEPT). NCEPT leverages [Formula: see text]B neutron capture, leading to the emission of detectable 478 keV photons. Experiments were performed at the Heavy Ion Medical Accelerator in Chiba, Japan, with two Poly(methyl methacrylate) (PMMA) targets, one bearing a boron insert. The BeNEdiCTE gamma-ray detector measured an increase in the 478 keV signal of 45 ± 7% and 26 ± 2% for carbon and helium ion irradiation, respectively. Our Geant4 Monte Carlo simulation model, developed to investigate photon origins, found less than 30% of detected photons originated from the insert, while boron in the detector's circuit boards contributed over 65%. Further, the model investigated detector sensitivity, establishing its capability to record a 10% increase in 478 keV photon detection at a target [Formula: see text]B concentration of 500 ppm using spectral windowing alone, and 25% when combined with temporal windowing. The linear response extended to concentrations up to 20,000 ppm. The increase in the signal in all evaluated cases confirm the potential of the proposed detector design for neutron capture quantification in NCEPT.

A Monte Carlo model of the Dingo thermal neutron imaging beamline.

In this study, we present a validated Geant4 Monte Carlo simulation model of the Dingo thermal neutron imaging beamline at the Australian Centre for Neutron Scattering. The model, constructed using CAD drawings of the entire beam transport path and shielding structures, is designed to precisely predict the in-beam neutron field at the position at the sample irradiation stage. The model's performance was assessed by comparing simulation results to various experimental measurements, including planar thermal neutron distribution obtained in-beam using gold foil activation and [Formula: see text]B[Formula: see text]C-coated microdosimeters and the out-of-beam neutron spectra measured with Bonner spheres. The simulation results demonstrated that the predicted neutron fluence at the field's centre is within 8.1% and 2.1% of the gold foil and [Formula: see text]B[Formula: see text]C-coated microdosimeter measurements, respectively. The logarithms of the ratios of average simulated to experimental fluences in the thermal (E[Formula: see text] 0.414 eV), epithermal (0.414 eV < E[Formula: see text] 11.7 keV) and fast (E[Formula: see text] 11.7 keV) spectral regions were approximately - 0.03 to + 0.1, - 0.2 to + 0.15, and - 0.4 to + 0.2, respectively. Furthermore, the predicted thermal, epithermal and fast neutron components in-beam at the sample stage position constituted approximately 18%, 64% and 18% of the total neutron fluence.

An inception network for positron emission tomography based dose estimation in carbon ion therapy.

Objective. We aim to evaluate a method for estimating 1D physical dose deposition profiles in carbon ion therapy via analysis of dynamic PET images using a deep residual learning convolutional neural network (CNN). The method is validated using Monte Carlo simulations of12C ion spread-out Bragg peak (SOBP) profiles, and demonstrated with an experimental PET image.Approach. A set of dose deposition and positron annihilation profiles for monoenergetic12C ion pencil beams in PMMA are first generated using Monte Carlo simulations. From these, a set of random polyenergetic dose and positron annihilation profiles are synthesised and used to train the CNN. Performance is evaluated by generating a second set of simulated12C ion SOBP profiles (one 116 mm SOBP profile and ten 60 mm SOBP profiles), and using the trained neural network to estimate the dose profile deposited by each beam and the position of the distal edge of the SOBP. Next, the same methods are used to evaluate the network using an experimental PET image, obtained after irradiating a PMMA phantom with a12C ion beam at QST's Heavy Ion Medical Accelerator in Chiba facility in Chiba, Japan. The performance of the CNN is compared to that of a recently published iterative technique using the same simulated and experimental12C SOBP profiles.Main results. The CNN estimated the simulated dose profiles with a mean relative error (MRE) of 0.7% ± 1.0% and the distal edge position with an accuracy of 0.1 mm ± 0.2 mm, and estimate the dose delivered by the experimental12C ion beam with a MRE of 3.7%, and the distal edge with an accuracy of 1.7 mm.Significance. The CNN was able to produce estimates of the dose distribution with comparable or improved accuracy and computational efficiency compared to the iterative method and other similar PET-based direct dose quantification techniques.

Detection and discrimination of neutron capture events for NCEPT dose quantification.

Neutron Capture Enhanced Particle Therapy (NCEPT) boosts the effectiveness of particle therapy by capturing thermal neutrons produced by beam-target nuclear interactions in and around the treatment site, using tumour-specific [Formula: see text]B or [Formula: see text]Gd-based neutron capture agents. Neutron captures release high-LET secondary particles together with gamma photons with energies of 478 keV or one of several energies up to 7.94 MeV, for [Formula: see text]B and [Formula: see text]Gd, respectively. A key requirement for NCEPT's translation is the development of in vivo dosimetry techniques which can measure both the direct ion dose and the dose due to neutron capture. In this work, we report signatures which can be used to discriminate between photons resulting from neutron capture and those originating from other processes. A Geant4 Monte Carlo simulation study into timing and energy thresholds for discrimination of prompt gamma photons resulting from thermal neutron capture during NCEPT was conducted. Three simulated [Formula: see text] mm[Formula: see text] cubic PMMA targets were irradiated by [Formula: see text]He or [Formula: see text]C ion beams with a spread out Bragg peak (SOBP) depth range of 60 mm; one target is homogeneous while the others include [Formula: see text] mm[Formula: see text] neutron capture inserts (NCIs) of pure [Formula: see text]B or [Formula: see text]Gd located at the distal edge of the SOBP. The arrival times of photons and neutrons entering a simulated [Formula: see text] mm[Formula: see text] ideal detector were recorded. A temporal mask of 50-60 ns was found to be optimal for maximising the discrimination of the photons resulting from the neutron capture by boron and gadolinium. A range of candidate detector and thermal neutron shielding materials were simulated, and detections meeting the proposed acceptance criteria (i.e. falling within the target energy window and arriving 60 ns post beam-off) were classified as true or false positives, depending on their origin. The ratio of true/false positives ([Formula: see text]) was calculated; for targets with [Formula: see text]B and [Formula: see text]Gd NCIs, the detector materials which resulted in the highest [Formula: see text] were cadmium-shielded CdTe and boron-shielded LSO, respectively. The optimal irradiation period for both carbon and helium ions was 1 µs for the [Formula: see text]B NCI and 1 ms for the [Formula: see text]Gd NCI.

A validated Geant4 model of a whole-body PET scanner with four-layer DOI detectors.

The purpose of this work is to develop a validated Geant4 simulation model of a whole-body prototype PET scanner constructed from the four-layer depth-of-interaction detectors developed at the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Japan. The simulation model emulates the behaviour of the unique depth of interaction sensing capability of the scanner without needing to directly simulate optical photon transport in the scintillator and photodetector modules. The model was validated by evaluating and comparing performance metrics from the NEMA NU 2-2012 protocol on both the simulated and physical scanner, including spatial resolution, sensitivity, scatter fraction, noise equivalent count rates and image quality. The results show that the average sensitivities of the scanner in the field-of-view were 5.9 cps kBq-1 and 6.0 cps kBq-1 for experiment and simulation, respectively. The average spatial resolutions measured for point sources placed at several radial offsets were 5.2± 0.7 mm and 5.0± 0.8 mm FWHM for experiment and simulation, respectively. The peak NECR was 22.9 kcps at 7.4 kBq ml-1 for the experiment, while the NECR obtained via simulation was 23.3 kcps at the same activity. The scatter fractions were 44% and 41.3% for the experiment and simulation, respectively. Contrast recovery estimates performed in different regions of a simulated image quality phantom matched the experimental results with an average error of -8.7% and +3.4% for hot and cold lesions, respectively. The results demonstrate that the developed Geant4 model reliably reproduces the key NEMA NU 2-2012 performance metrics evaluated on the prototype PET scanner. A simplified version of the model is included as an advanced example in Geant4 version 10.5.

Dose quantification in carbon ion therapy using in-beam positron emission tomography.

This work presents an iterative method for the estimation of the absolute dose distribution in patients undergoing carbon ion therapy, via analysis of the distribution of positron annihilations resulting from the decay of positron-emitting fragments created in the target volume. The proposed method relies on the decomposition of the total positron-annihilation distributions into profiles of the three principal positron-emitting fragment species - 11C, 10C and 15O. A library of basis functions is constructed by simulating a range of monoenergetic 12C ion irradiations of a homogeneous polymethyl methacrylate phantom and measuring the resulting one-dimensional positron-emitting fragment profiles and dose distributions. To estimate the dose delivered during an arbitrary polyenergetic irradiation, a linear combination of factors from the fragment profile library is iteratively fitted to the decomposed positron annihilation profile acquired during the irradiation, and the resulting weights combined with the corresponding monoenergetic dose profiles to estimate the total dose distribution. A total variation regularisation term is incorporated into the fitting process to suppress high-frequency noise. The method was evaluated with 14 different polyenergetic 12C dose profiles in a polymethyl methacrylate target: one which produces a flat biological dose, 10 with randomised energy weighting factors, and three with distinct dose maxima or minima within the spread-out Bragg peak region. The proposed method is able to calculate the dose profile with mean relative errors of 0.8%, 1.0% and 1.6% from the 11C, 10C, 15O fragment profiles, respectively, and estimate the position of the distal edge of the SOBP to within an average of 0.7 mm, 1.9 mm and 1.2 mm of its true location.

Experimental investigation of the characteristics of radioactive beams for heavy ion therapy.

PURPOSE: This work has two related objectives. The first is to estimate the relative biological effectiveness of two radioactive heavy ion beams based on experimental measurements, and compare these to the relative biological effectiveness of corresponding stable isotopes to determine whether they are therapeutically equivalent. The second aim is to quantitatively compare the quality of images acquired postirradiation using an in-beam whole-body positron emission tomography scanner for range verification quality assurance. METHODS: The energy deposited by monoenergetic beams of 11 C at 350 MeV/u, 15 O at 250 MeV/u, 12 C at 350 MeV/u, and 16 O at 430 MeV/u was measured using a cruciform transmission ionization chamber in a water phantom at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. Dose-mean lineal energy was measured at various depths along the path of each beam in a water phantom using a silicon-on-insulator mushroom microdosimeter. Using the modified microdosimetric kinetic model, the relative biological effectiveness at 10% survival fraction of the radioactive ion beams was evaluated and compared to that of the corresponding stable ions along the path of the beam. Finally, the postirradiation distributions of positron annihilations resulting from the decay of positron-emitting nuclei were measured for each beam in a gelatin phantom using the in-beam whole-body positron emission tomography scanner at HIMAC. The depth of maximum positron-annihilation density was compared with the depth of maximum dose deposition and the signal-to-background ratios were calculated and compared for images acquired over 5 and 20 min postirradiation of the phantom. RESULTS: In the entrance region, the h b o x RBE 10 was 1.2 ± 0.1 for both 11 C and 12 C beams, while for 15 O and 16 O it was 1.4 ± 0.1 and 1.3 ± 0.1, respectively. At the Bragg peak, the RBE 10 was 2.7 ± 0.4 for 11 C and 2.9 ± 0.4 for 12 C, while for 15 O and 16 O it was 2.7 ± 0.4 and 2.8 ± 0.4, respectively. In the tail region, RBE 10 could only be evaluated for carbon; the RBE 10 was 1.6 ± 0.2 and 1.5 ± 0.1 for 11 C and 12 C, respectively. Positron emission tomography images obtained from gelatin targets irradiated by radioactive ion beams exhibit markedly improved signal-to-background ratios compared to those obtained from targets irradiated by nonradioactive ion beams, with 5-fold and 11-fold increases in the ratios calculated for the 15 O and 11 C images compared with the values obtained for 16 O and 12 C, respectively. The difference between the depth of maximum dose and the depth of maximum positron annihilation density is 2.4 ± 0.8 mm for 11 C, compared to -5.6 ± 0.8 mm for 12 C and 0.9 ± 0.8 mm for 15 O vs -6.6 ± 0.8 mm for 16 O. CONCLUSIONS: The RBE 10 values for 11 C and 15 O were found to be within the 95% confidence interval of the RBEs estimated for their corresponding stable isotopes across each of the regions in which it was evaluated. Furthermore, for a given dose, 11 C and 15 O beams produce much better quality images for range verification compared with 12 C and 16 O, in particular with regard to estimating the location of the Bragg peak.

Influence of momentum acceptance on range monitoring of 11C and 15O ion beams using in-beam PET.

In heavy-ion therapy, the stopping position of primary ions in tumours needs to be monitored for effective treatment and to prevent overdose exposure to normal tissues. Positron-emitting ion beams, such as 11C and 15O, have been suggested for range verification in heavy-ion therapy using in-beam positron emission tomography (PET) imaging, which offers the capability of visualizing the ion stopping position with a high signal-to-noise ratio. We have previously demonstrated the feasibility of in-beam PET imaging for the range verification of 11C and 15O ion beams and observed a slight shift between the beam stopping position and the dose peak position in simulations, depending on the initial beam energy spread. In this study, we focused on the experimental confirmation of the shift between the Bragg peak position and the position of the maximum detected positron-emitting fragments via a PET system for positron-emitting ion beams of 11C (210 MeV u-1) and 15O (312 MeV u-1) with momentum acceptances of 5% and 0.5%. For this purpose, we measured the depth doses and performed in-beam PET imaging using a polymethyl methacrylate (PMMA) phantom for both beams with different momentum acceptances. The shifts between the Bragg peak position and the PET peak position in an irradiated PMMA phantom for the 15O ion beams were 1.8 mm and 0.3 mm for momentum acceptances of 5% and 0.5%, respectively. The shifts between the positions of two peaks for the 11C ion beam were 2.1 mm and 0.1 mm for momentum acceptances of 5% and 0.5%, respectively. We observed larger shifts between the Bragg peak and the PET peak positions for a momentum acceptance of 5% for both beams, which is consistent with the simulation results reported in our previous study. The biological doses were also estimated from the calculated relative biological effectiveness (RBE) values using a modified microdosimetric kinetic model (mMKM) and Monte Carlo simulation. Beams with a momentum acceptance of 5% should be used with caution for therapeutic applications to avoid extra dose to normal tissues beyond the tumour when the dose distal fall-off is located beyond the treatment volume.

Optimisation of monolithic nanocomposite and transparent ceramic scintillation detectors for positron emission tomography.

High-resolution arrays of discrete monocrystalline scintillators used for gamma photon coincidence detection in PET are costly and complex to fabricate, and exhibit intrinsically non-uniform sensitivity with respect to emission angle. Nanocomposites and transparent ceramics are two alternative classes of scintillator materials which can be formed into large monolithic structures, and which, when coupled to optical photodetector arrays, may offer a pathway to low cost, high-sensitivity, high-resolution PET. However, due to their high optical attenuation and scattering relative to monocrystalline scintillators, these materials exhibit an inherent trade-off between detection sensitivity and the number of scintillation photons which reach the optical photodetectors. In this work, a method for optimising scintillator thickness to maximise the probability of locating the point of interaction of 511 keV photons in a monolithic scintillator within a specified error bound is proposed and evaluated for five nanocomposite materials (LaBr3:Ce-polystyrene, Gd2O3-polyvinyl toluene, LaF3:Ce-polystyrene, LaF3:Ce-oleic acid and YAG:Ce-polystyrene) and four ceramics (GAGG:Ce, GLuGAG:Ce, GYGAG:Ce and LuAG:Pr). LaF3:Ce-polystyrene and GLuGAG:Ce were the best-performing nanocomposite and ceramic materials, respectively, with maximum sensitivities of 48.8% and 67.8% for 5 mm localisation accuracy with scintillator thicknesses of 42.6 mm and 27.5 mm, respectively.

Comparative study of alternative Geant4 hadronic ion inelastic physics models for prediction of positron-emitting radionuclide production in carbon and oxygen ion therapy.

The distribution of fragmentation products predicted by Monte Carlo simulations of heavy ion therapy depend on the hadronic physics model chosen in the simulation. This work aims to evaluate three alternative hadronic inelastic fragmentation physics options available in the Geant4 Monte Carlo radiation physics simulation framework to determine which model most accurately predicts the production of positron-emitting fragmentation products observable using in-beam PET imaging. Fragment distributions obtained with the BIC, QMD, and INCL + + physics models in Geant4 version 10.2.p03 are compared to experimental data obtained at the HIMAC heavy-ion treatment facility at NIRS in Chiba, Japan. For both simulations and experiments, monoenergetic beams are applied to three different block phantoms composed of gelatin, poly(methyl methacrylate) and polyethylene. The yields of the positron-emitting nuclei 11C, 10C and 15O obtained from simulations conducted with each model are compared to the experimental yields estimated by fitting a multi-exponential radioactive decay model to dynamic PET images using the normalised mean square error metric in the entrance, build up/Bragg peak and tail regions. Significant differences in positron-emitting fragment yield are observed among the three physics models with the best overall fit to experimental 12C and 16O beam measurements obtained with the BIC physics model.

Performance evaluation of a whole-body prototype PET scanner with four-layer DOI detectors.

Parallax error caused by the detector crystal thickness degrades spatial resolution at the peripheral regions of the field-of-view (FOV) of a scanner. To resolve this issue, depth-of-interaction (DOI) measurement is a promising solution to improve the spatial resolution and its uniformity over the entire FOV. Even though DOI detectors have been used in dedicated systems with a small ring diameter such as for the human brain, breast and small animals, the use of DOI detectors for a large bore whole-body PET system has not been demonstrated yet. We have developed a four-layered DOI detector, and its potential for a brain dedicated system has been proven in our previous development. In the present work, we investigated the use of the four-layer DOI detector for a large bore PET system by developing the world's first whole-body prototype. We evaluated its performance characteristics in accordance with the NEMA NU 2 standard. Furthermore, the impact of incorporating DOI information was evaluated with the NEMA NU 4 image quality phantom. Point source images were reconstructed with a filtered back projection (FBP), and an average spatial resolution of 5.2 ± 0.7 mm was obtained. For the FBP image, the four-layer DOI information improved the radial spatial resolution by 48% at the 20 cm offset position. The peak noise-equivalent count rate (NECR) was 22.9 kcps at 7.4 kBq ml-1 and the scatter fraction was 44%. The system sensitivity was 5.9 kcps MBq-1. For the NEMA NU 2 image quality phantom, the 10 mm sphere was clearly visualized without any artifacts. For the NEMA NU 4 image quality phantom, we measured the phantom at 0, 10 and 20 cm offset positions. As a result, we found the image with four-layer DOI could visualize the 2 mm-diameter hot cylinder although it could not be recognized on the image without DOI. The average improvements in the recovery coefficients for the five hot rods (1-5 mm) were 0.3%, 4.4% and 26.3% at the 0, 10 and 20 cm offset positions, respectively (except for the 1 mm-diameter rod at the 20 cm offset position). Although several practical issues (such as adding end-shields) remain to be addressed before the scanner is ready for clinical use, we showed that the four-layer DOI technology provided higher and more uniform spatial resolution over the FOV and improved contrast for small uptake regions located at the peripheral FOV, which could improve detectability of small and distal lesions such as nodal metastases, especially in obese patients.

Monte Carlo investigation of the characteristics of radioactive beams for heavy ion therapy.

This work presents a simulation study evaluating relative biological effectiveness at 10% survival fraction (RBE10) of several different positron-emitting radionuclides in heavy ion treatment systems, and comparing these to the RBE10s of their non-radioactive counterparts. RBE10 is evaluated as a function of depth for three positron-emitting radioactive ion beams (10C, 11C and 15O) and two stable ion beams (12C and 16O) using the modified microdosimetric kinetic model (MKM) in a heterogeneous skull phantom subject to a rectangular 50 mm × 50 mm × 60 mm spread out Bragg peak. We demonstrate that the RBE10 of the positron-emitting radioactive beams is almost identical to the corresponding stable isotopes. The potential improvement in PET quality assurance image quality which is obtained when using radioactive beams is evaluated by comparing the signal to background ratios of positron annihilations at different intra- and post-irradiation time points. Finally, the incidental dose to the patient resulting from the use of radioactive beams is also quantified and shown to be negligible.

Localisation of the Lines of Response in a Continuous Cylindrical Shell PET Scanner.

This work presents a technique for localising the endpoints of the lines of response in a PET scanner based on a continuous cylindrical shell scintillator. The technique is demonstrated by applying it to a simulation of a sensitivity-optimised continuous cylindrical shell PET system using two novel scintillator materials - a transparent ceramic garnet, GLuGAG:Ce, and a LuF3:Ce-polystyrene nanocomposite. Error distributions for the endpoints of the lines of response in the axial, tangential and radial dimension as well as overall endpoint spatial error are calculated for three source positions; the resultant distribution of error in the placement of the lines of response is also estimated.

Opportunistic dose amplification for proton and carbon ion therapy via capture of internally generated thermal neutrons.

This paper presents Neutron Capture Enhanced Particle Therapy (NCEPT), a method for enhancing the radiation dose delivered to a tumour relative to surrounding healthy tissues during proton and carbon ion therapy by capturing thermal neutrons produced inside the treatment volume during irradiation. NCEPT utilises extant and in-development boron-10 and gadolinium-157-based drugs from the related field of neutron capture therapy. Using Monte Carlo simulations, we demonstrate that a typical proton or carbon ion therapy treatment plan generates an approximately uniform thermal neutron field within the target volume, centred around the beam path. The tissue concentrations of neutron capture agents required to obtain an arbitrary 10% increase in biological effective dose are estimated for realistic treatment plans, and compared to concentrations previously reported in the literature. We conclude that the proposed method is theoretically feasible, and can provide a worthwhile improvement in the dose delivered to the tumour relative to healthy tissue with readily achievable concentrations of neutron capture enhancement drugs.

A simulation study of BrachyShade, a shadow-based internal source tracking system for HDR prostate brachytherapy.

This paper presents a simulation study of BrachyShade, a proposed internal source-tracking system for real time quality assurance in high dose rate prostate brachytherapy. BrachyShade consists of a set of spherical tungsten occluders located above a pixellated silicon photodetector. The source location is estimated by minimising the mean squared error between a parametric model of the shadow image and acquired images of the shadows projected on the detector plane. A novel algorithm is finally employed to correct the systemic error resulting from Compton scattering in the medium. The worst-case error obtained with BrachyShade for a 13.5 ms image acquisition is less than 1.3 mm in the most distant part of the treatment volume, while for 75% of source locations an error of less than 0.42 mm was achieved.

Semiconductor real-time quality assurance dosimetry in brachytherapy.

With the increase in complexity of brachytherapy treatments, there has been a demand for the development of sophisticated devices for delivery verification. The Centre for Medical Radiation Physics (CMRP), University of Wollongong, has demonstrated the applicability of semiconductor devices to provide cost-effective real-time quality assurance for a wide range of brachytherapy treatment modalities. Semiconductor devices have shown great promise to the future of pretreatment and in vivo quality assurance in a wide range of brachytherapy treatments, from high-dose-rate (HDR) prostate procedures to eye plaque treatments. The aim of this article is to give an insight into several semiconductor-based dosimetry instruments developed by the CMRP. Applications of these instruments are provided for breast and rectal wall in vivo dosimetry in HDR brachytherapy, urethral in vivo dosimetry in prostate low-dose-rate (LDR) brachytherapy, quality assurance of HDR brachytherapy afterloaders, HDR pretreatment plan verification, and real-time verification of LDR and HDR source dwell positions.

Microdosing, isotopic labeling, radiotracers and metabolomics: relevance in drug discovery, development and safety.

This review discusses the use of stable (13C, 2D) or radioactive isotopes (14C, 11C, 18F, 131I, 64Cu, 68Ga) incorporated into the molecular structure of new drug entities for the purpose of pharmacokinetic or -dynamic studies. Metabolite in safety testing requires the administration of pharmacologically active doses. In such studies, radiotracers find application mainly in preclinical animal investigations, whereby LC-MS/MS is used to identify metabolite structure and drug-related effects. In contrast, first-in-human metabolite studies have to be carried out at nonpharmacological doses not exceeding 100 µg (microdose), which is generally too low for metabolite detection by LC-MS/MS. This short-coming can be overcome by specific radio- or isotopic labeling of the drug of interest and measurements using accelerator mass spectroscopy, single-photon emission computed tomography and positron emission tomography. Such combined radioisotope-based approaches permit Phase 0, first-in-human metabolite study.