Fluorine-18 labeling PEGylated 6-boronotryptophan for PET scanning of mice for assessing the pharmacokinetics for boron neutron capture therapy of brain tumors.

Two tryptophan compound classes 5- and 6-borono PEGylated boronotryptophan derivatives have been prepared for assessing their aqueous solubility as formulation of injections for boron neutron capture therapy (BNCT). The PEGylation has improved their aqueous solubility thereby increasing their test concentration in 1 mM without suffering from toxicity. In-vitro uptake assay of PEGylated 5- and 6-boronotryptophan showed that the B-10 concentration can reach 15-50 ppm in U87 cell whereas the uptake in LN229 cell varies. Shorter PEG compound 6-boronotryptophanPEG200[18F] was obtained in 1.7 % radiochemical yield and the PET-derived radioradioactivity percentage in 18 % was taken up by U87 tumor at the limb of xenograft mouse. As high as tumor to normal uptake ratio in 170 (T/N) was obtained while an inferior radioactivity uptake of 3 % and T/N of 8 was observed in LN229 xenografted mouse.

Comparing the effects of various (p,xn) radionuclide production routes on induced radioactivity in the concrete walls of a cyclotron vault.

In sum, 11 (p,xn) related nuclear reactions with 9 target materials, namely 18O(p,n)18F, 15N(p,n)15O, 68Zn(p,n)68Ga, 68Zn(p,2n)67Ga, 69Ga(p,2n)68Ge, 89Y(p,n)89Zr, 100Mo(p,pn)99Mo, 100Mo(p,2n)99mTc, 112Cd(p,2n)111In, 124Xe(p,2n)123Cs and 203Tl(p,3n)201Pb, are involved in the operation of 13 radionuclide-production cyclotrons in Taiwan. The secondary neutrons accompanying these production routes could induce varying degrees of material activation in the cyclotron facility. Accordingly, this study compared the effects of various (p,xn) production routes on the neutron-induced long-lived radioactivity in the concrete walls of a hypothetical cyclotron vault. In addition, an activation-reduction approach involving the addition of a layer of neutron-absorbing material to the surface of inner concrete walls was evaluated.

Shielding analysis of the proton therapy facility at China Medical University Hospital: comparison of a simplified approach with Monte Carlo simulations.

This study comprehensively compared two approaches for analyzing the shielding design of the proton therapy facility at China Medical University Hospital. The first approach essentially involved two approximate models: one for estimating the transmitted radiation through thick shields, and one for estimating radiation streaming at locations near a maze entrance. The second approach relied on Monte Carlo simulations for predicting the radiation field in a complex environment. A total of 22 beam loss scenarios were considered, and dose rates at 32 locations around the facility were estimated using the two approaches. The comparison results demonstrated that the simplified approach proposed in this study can yield fairly accurate or conservative estimates for quickly performing shielding design or dose assessment in a real-world proton therapy facility.

Automated Workflow for Calculating the Collective and Average Effective Doses of Galactic Cosmic Radiation Received by Pilots in Taiwan from 2006 to 2021.

ABSTRACT: On the basis of statistical data obtained from publicly available annual civil aviation reports, we developed an automated workflow for estimating the overall radiation exposure of aircraft pilots caused by galactic cosmic radiation. The workflow comprises several data-processing scripts that work with the batch analysis capability built in the NTHU Flight Dose Calculator . This method can quickly provide best possible estimates of the annual collective and average effective doses received by pilots of various airlines because all passenger, cargo, and charter flights operated that year were considered rather than some selected flights. The workflow and its implementation as well as analysis of results for the period of 2006-2021 are discussed herein. The results revealed that in 2019, six airlines in Taiwan operated 479 separate flight segments with 226 aircraft. The collective effective dose received by all 2,986 pilots was approximately 5,536 person-mSv; hence, the average individual effective dose was 1.85 mSv. During the COVID-19 pandemic, the doses decreased by more than half. In 2020, the collective effective dose received by all 2,936 pilots decreased sharply to 2,527 person-mSv, corresponding to an average effective dose per pilot of only 0.86 mSv. During 2006-2019, the annual average effective dose per pilot in Taiwan was between 1.65 and 2.71 mSv, and the average effective dose rate per flight hour was 3.15 µSv h. -1.

Simulation of cosmic rays inside an aircraft: spectral perturbation and dose reduction due to aircraft structures and contents.

In this study, an intricate combinatorial geometry model of a Boeing 777-300ER aircraft was constructed for Monte Carlo transport simulations. The aircraft-induced perturbations of the energy spectra and effective doses of secondary cosmic rays at a typical civil aviation altitude (10 km) were investigated on a component-by-component basis, which included neutrons, protons, photons, electrons, positrons, muons and charged pions. Two geomagnetic cutoff rigidities (1.35 and 15.53 GV) and two solar modulation parameters (430 and 1360 MV) were considered in the aforementioned simulations. The characteristics of various cosmic-ray components at six locations along the fuselage were assessed and compared with those of an unperturbed radiation field in the atmosphere. Aircraft structures and contents reduced the effective doses of personnel inside the aircraft to varying degrees, up to an ~32% reduction in the middle section of the passenger cabin. On average, the dose reduction was ~12-16% depending on geomagnetic and solar conditions. Quantifying the aircraft's self-shielding effects can further improve the estimation accuracy of aircrew and passengers' exposure to cosmic radiation. Information regarding the perturbed energy spectra of cosmic rays may be useful for designing onboard experiments or analyzing onboard measurement data.

Antiinflammation Derived Suzuki-Coupled Fenbufens as COX-2 Inhibitors: Minilibrary Construction and Bioassay.

A small fenbufen library comprising 18 compounds was prepared via Suzuki Miyara coupling. The five-step preparations deliver 9-17% biphenyl compounds in total yield. These fenbufen analogs exert insignificant activity against the IL-1 release as well as inhibiting cyclooxygenase 2 considerably. Both the para-amino and para-hydroxy mono substituents display the most substantial COX-2 inhibition, particularly the latter one showing a comparable activity as celecoxib. The most COX-2 selective and bioactive disubstituted compound encompasses one electron-withdrawing methyl and one electron-donating fluoro groups in one arene. COX-2 is selective but not COX-2 to bioactive compounds that contain both two electron-withdrawing groups; disubstituted analogs with both resonance-formable electron-donating dihydroxy groups display high COX-2 activity but inferior COX-2 selectivity. In silico simulation and modeling for three COX-2 active-p-fluoro, p-hydroxy and p-amino-fenbufens show a preferable docking to COX-2 than COX-1. The most stabilization by the p-hydroxy fenbufen with COX-2 predicted by theoretical simulation is consistent with its prominent COX-2 inhibition resulting from experiments.

Ratios of Eye Lens and Hand Equivalent Doses with Whole-Body Effective Doses for Operators Performing Interventional Radiological Procedures.

ABSTRACT: Estimating radiation doses for operators performing interventional radiological procedures is crucial in the occupational radiation protection of medical staff. In this study, Monte Carlo simulations coupled with an anthropomorphic phantom were used to model various exposure scenarios during the procedures. Conversion coefficients of the dose-area product of x rays for the eye lens equivalent dose, hand equivalent dose, and whole-body effective dose of the operator were calculated. Accordingly, the relationships between these dose quantities in typical interventional configurations were established, considering various source locations, tube voltages, and use of protective equipment or not. The results are presented in a systematic way for easy comparison and use. Tables and figures of the data can be helpful to provide estimates of eye lens and hand equivalent doses when records of specific dosimeters are absent, such as in the retrospective assessment of operators' eye lens and hand equivalent doses in past practices.

A Comprehensive Approach for Estimating Collective and Average Effective Doses of Galactic Cosmic Radiation Received by Pilots.

This study proposes a feasible and comprehensive approach for estimating collective and average effective doses of galactic cosmic radiation received by pilots on the basis of data in publicly available civil aviation annual statistical reports. Large uncertainties are associated with the estimation of these quantities because the radiation environment at aviation altitudes is complex, and a large number of flights operated by various air carriers is involved. A best estimate can be obtained through this approach because it considers all passenger, cargo, and charter flights operated during a long period of time instead of subjectively selecting some representative flights for dose evaluation. The approach becomes feasible and practical with the aid of a special feature called automatic batch analysis in the NTHU Flight Dose Calculator. There are two international airlines in Taiwan: China Airlines and EVA Air. As a demonstration, the collective effective dose received by the 2,513 pilots from the two airlines in 2018 was estimated to be 4,947 person-mSv, and the average effective dose per pilot was 1.97 mSv. These estimates were considered representative because they were based on all 151,526 flight segments operated that year. The assessment of the annual effective doses received by pilots in Taiwan from 2006 to 2018 was performed. The results varied in the range of 1.70-2.97 mSv because of variations in solar activity and operational flight routes. A regression model that can effectively reproduce the derived average effective dose rates on board aircraft was obtained for future application in aircrew dosimetry.

Comparison of different methods for the shielding analysis of an AB-BNCT facility based on the Be(p,xn) reaction with 30-MeV protons.

Five shielding calculation methods were employed to estimate the dose rate distribution around an accelerator-based boron neutron capture therapy facility. Their performances were compared in terms of accuracy and efficiency. The results indicate that the hybrid deterministic/Monte Carlo method is the most efficient in the context of accurate modeling and simulation, whereas the analytical approximation with pre-generated source terms and attenuation lengths is preferable in the design phase because of its simplicity and ease of verification while retaining a reasonable accuracy.

Determining and Comparing Neutron Spectra at Taiwan Photon Source before and after the Installation of Local Injection Shielding.

Accurate neutron spectrum measurements at light source facilities are difficult to perform because of relatively low and time-varying neutron intensities. A homemade Bonner cylinder spectrometer was used to determine the energy spectra of neutrons outside the lateral shielding wall of the Taiwan Photon Source before and after the installation of local injection shielding. The spectrometer, similar to the design of conventional Bonner spheres, features (1) highly sensitive neutron detection and (2) a wide-range response to neutrons with energies up to the GeV range. Neutron measurements were conducted by intentionally parking the injected 3-GeV electrons at the septum of the storage ring. On the basis of high-fidelity FLUKA simulations, neutron spectra at the measurement location under the experimental conditions were obtained and adopted as an initial guess for spectrum unfolding. The neutron spectra determined before and after the local shielding were comprehensively compared in terms of their intensities and characteristics. The local shielding resulted in overall reductions of approximately 44% and 38% in total neutron flux and dose rate, respectively. Both before and after the local shielding, high-energy neutrons (>10 MeV) were the dominant component of the radiation field, which contributed approximately 30% to 35% of the total neutron flux and 55% to 59% of the total neutron dose rate.

EFFECTS OF FLIGHT ROUTE VARIATION AND GREAT-CIRCLE APPROXIMATION ON AVIATION DOSE ASSESSMENT FOR POPULAR FLIGHTS FROM TAIWAN.

Galactic cosmic-ray-induced secondary particles in the atmosphere constitute an important source of radiation exposure to airline crews and passengers. In this study, a systematic dose assessment was conducted for 11 popular flights from Taiwan, with an emphasis on the effects of flight route variation and assumption. The case studies covered a broad range of commercial flights departing from Taipei, from a domestic flight of <1 h to a long-haul international flight of more than 14 h. For each route under study, information on 100 actual flight routes was retrieved from flight tracking data collected from June to September 2017, and the information was analyzed using a self-developed program called the 'NTHU Flight Dose Calculator'. The resulting distribution of route doses provided not only the mean value and associated standard deviation but also information on the characteristics of aviation dose assessment and management. Furthermore, compared with actual flight routes, the dose differences introduced by great-circle approximation were evaluated, and the effects of solar activity on the dose assessment of these flights were reported.

SCOPING ANALYSIS OF MATERIAL ACTIVATION AT A BORON NEUTRON CAPTURE THERAPY FACILITY BASED ON THE Be(p,xn) REACTION WITH 30 MeV PROTONS.

Material activation assessment of a proposed accelerator-based boron neutron capture therapy facility was performed using the FLUKA Monte Carlo code to quantify the magnitude of the problem in terms of the isotope inventories, induced activities, and residual dose rates. Two simplified operation scenarios were considered: a 30-min proton bombardment to simulate a typical session of patient treatment and a long-term 1 year continuous operation to estimate the accumulation of long-lived radionuclides. Following the generation and transport of decay radiation, the space- and time-dependent inventories of induced radionuclides in materials and residual dose rates after shutdown were obtained. The predicted results were compared with the corresponding regulatory limits. Moreover, the effectiveness of various measures to reduce the impact of material activation was demonstrated.

STUDIES OF COSMIC-RAY MUONS AND NEUTRONS IN A FIVE-STORY CONCRETE BUILDING.

This study thoroughly determined the flux and dose rate distributions of cosmic-ray muons and neutrons in a five-story concrete building by comparing measurements with Monte Carlo simulations of cosmic-ray showers. An angular-energy-dependent surface source comprising secondary muons and neutrons at a height of 200 m above ground level was established and verified, which was used to concatenate the shower development in the upper atmosphere with subsequent simulations of radiation transport down to ground level, including the effect of the terrain and studied building. A Berkeley Lab cosmic-ray detector and a highly sensitive Bonner cylinder were used to perform muon and neutron measurements on each building floor. After careful calibration and correction, the measured responses of the two detectors were discovered to be reasonably consistent with the theoretical predictions, thus confirming the validity of the two-step calculation model employed in this study. The annual effective doses from cosmic-ray muons and neutrons on the open roof of the building were estimated to be 115.2 and 35.2 µSv, respectively. Muons and neutrons were attenuated floor-by-floor with different attenuation factors of 0.97 and 0.78, and their resultant dose rates on the first floor of the building were 97.8 and 9.9 µSv, respectively.

DEVELOPMENT, VALIDATION AND DEMONSTRATION OF THE NTHU FLIGHT DOSE CALCULATOR.

Galactic cosmic-ray-induced air showers constitute the largest source of radiation exposure for aircrew and passengers. To facilitate the evaluation of effective doses received by this population, a database containing dose rates of various radiation components in the atmosphere was established; the parameterization accounted for altitude, geomagnetic rigidity and solar modulation. Energy spectra of secondary cosmic rays and effective dose rates were calculated using the FLUKA Monte Carlo code. An auxiliary MATLAB program with a graphical user interface was developed to estimate the aviation route dose through interpolation and integration. The dose calculator was benchmarked by comparing its predictions with data from other assessments. Finally, a set of representative flight routes of substantial interest in Taiwan was selected and evaluated.

COMPARING TWO MEASUREMENTS OF THE SAME COSMIC-RAY NEUTRON SPECTRUM USING STANDARD BONNER SPHERES AND HIGH-SENSITIVITY BONNER CYLINDERS.

Ground-level cosmic-ray neutron spectra in Taiwan were measured using two neutron spectrometers, standard Bonner spheres and homemade high-sensitivity Bonner cylinders. The Bonner sphere system consisted of 12 polyethylene spheres of various diameters and four extended-range spheres that contained embedded metal shells. A set of 16 similarly designed Bonner cylinders was assembled based on a large cylindrical 3He proportional counter, showing an efficiency ~18 times higher than that of the central probe of the Bonner spheres. However, these Bonner cylinders were not fully symmetrical and exhibited angular dependence in their responses to incoming neutrons. Focusing on the low-intensity neutron background, this study presents a systematic comparison between Bonner spheres and cylinders in terms of their response characteristics, counting statistics, and unfolded neutron spectra. The comparison indicated that the neutron probe of the Bonner spheres had a small but non-negligible counting noise that required subtraction from the recorded data. According to the response functions calculated for isotropic neutron incidence, the neutron spectrum determined using the high-sensitivity Bonner cylinders agreed well with that measured using the Bonner spheres. The annual effective doses from cosmic-ray neutrons at the location were determined to be 30.5 and 30.8 µSv by using the Bonner sphere and cylinder spectrometers, respectively, which corresponded to respective total neutron fluxes of 5.39 × 10-3 and 5.43 × 10-3 cm-2s-1.

Robust artificial neural network for reliability and sensitivity analyses of complex non-linear systems.

Artificial Neural Networks (ANNs) are commonly used in place of expensive models to reduce the computational burden required for uncertainty quantification, reliability and sensitivity analyses. ANN with selected architecture is trained with the back-propagation algorithm from few data representatives of the input/output relationship of the underlying model of interest. However, different performing ANNs might be obtained with the same training data as a result of the random initialization of the weight parameters in each of the network, leading to an uncertainty in selecting the best performing ANN. On the other hand, using cross-validation to select the best performing ANN based on the ANN with the highest R2 value can lead to biassing in the prediction. This is as a result of the fact that the use of R2 cannot determine if the prediction made by ANN is biased. Additionally, R2 does not indicate if a model is adequate, as it is possible to have a low R2 for a good model and a high R2 for a bad model. Hence, in this paper, we propose an approach to improve the robustness of a prediction made by ANN. The approach is based on a systematic combination of identical trained ANNs, by coupling the Bayesian framework and model averaging. Additionally, the uncertainties of the robust prediction derived from the approach are quantified in terms of confidence intervals. To demonstrate the applicability of the proposed approach, two synthetic numerical examples are presented. Finally, the proposed approach is used to perform a reliability and sensitivity analyses on a process simulation model of a UK nuclear effluent treatment plant developed by National Nuclear Laboratory (NNL) and treated in this study as a black-box employing a set of training data as a test case. This model has been extensively validated against plant and experimental data and used to support the UK effluent discharge strategy.

Neutron yield and induced radioactivity: a study of 235-MeV proton and 3-GeV electron accelerators.

This study evaluated the magnitude of potential neutron yield and induced radioactivity of two new accelerators in Taiwan: a 235-MeV proton cyclotron for radiation therapy and a 3-GeV electron synchrotron serving as the injector for the Taiwan Photon Source. From a nuclear interaction point of view, neutron production from targets bombarded with high-energy particles is intrinsically related to the resulting target activation. Two multi-particle interaction and transport codes, FLUKA and MCNPX, were used in this study. To ensure prediction quality, much effort was devoted to the associated benchmark calculations. Comparisons of the accelerators' results for three target materials (copper, stainless steel and tissue) are presented. Although the proton-induced neutron yields were higher than those induced by electrons, the maximal neutron production rates of both accelerators were comparable according to their respective beam outputs during typical operation. Activation products in the targets of the two accelerators were unexpectedly similar because the primary reaction channels for proton- and electron-induced activation are (p,pn) and (γ,n), respectively. The resulting residual activities and remnant dose rates as a function of time were examined and discussed.

Comparing dose rates near a radioactive patient evaluated using various source models: point, line, cylinder, and anthropomorphic phantoms.

This study investigated radiation exposures from nuclear medicine patients by systematically comparing the dose rates calculated using various source models, ranging from simplified point, line, and cylinder sources to high-quality anthropomorphic phantoms. Three widely used radionuclides, (99m)Tc, (18)F, and I(131), were considered in these source models with uniform or organ-dependent distributions. Conducting Monte Carlo simulations with anthropomorphic phantoms is a realistic but time-consuming approach. The point source model is simple but too conservative, overestimating dose rates by approximately a factor of 2 at a distance of 30 cm and by 30-40% at 1 m. Both the line and cylinder source models provided improved estimates, reducing the overestimation of dose rates to 10-20% at distances of interest. The line source model was comparable to the cylinder source model because of the offset of two competing effects (i.e., attenuation and buildup) caused by the source volume. The influence of various photon energies and cylinder sizes on the result of compensating errors was examined to evaluate the effective range of the line source model. The line source model, which is relatively easy to implement and predicts slightly conservative dose rates, is considered the most practical method for calculating dose rates near radioactive patients. An application of the line source model to 51 post-thyroidectomy patients in Taiwan was demonstrated. The consistency between calculations and measurements was satisfactory after considering the room-scattering effect.

Shielding analysis of proton therapy accelerators: a demonstration using Monte Carlo-generated source terms and attenuation lengths.

Monte Carlo simulations are generally considered the most accurate method for complex accelerator shielding analysis. Simplified models based on point-source line-of-sight approximation are often preferable in practice because they are intuitive and easy to use. A set of shielding data, including source terms and attenuation lengths for several common targets (iron, graphite, tissue, and copper) and shielding materials (concrete, iron, and lead) were generated by performing Monte Carlo simulations for 100-300 MeV protons. Possible applications and a proper use of the data set were demonstrated through a practical case study, in which shielding analysis on a typical proton treatment room was conducted. A thorough and consistent comparison between the predictions of our point-source line-of-sight model and those obtained by Monte Carlo simulations for a 360° dose distribution around the room perimeter showed that the data set can yield fairly accurate or conservative estimates for the transmitted doses, except for those near the maze exit. In addition, this study demonstrated that appropriate coupling between the generated source term and empirical formulae for radiation streaming can be used to predict a reasonable dose distribution along the maze. This case study proved the effectiveness and advantage of applying the data set to a quick shielding design and dose evaluation for proton therapy accelerators.

Evaluation of the root and root canal systems of mandibular first premolars in northern Taiwanese patients using cone-beam computed tomography.

BACKGROUND/PURPOSE: Cone-beam computed tomography (CBCT) can provide valuable data for root canal systems of human teeth in vivo. This study used CBCT to evaluate the number of roots and canals of 300 mandibular first premolars in 150 northern Taiwanese patients. METHODS: The root canal systems of 300 mandibular first premolars in 150 northern Taiwanese patients with bilateral premolars were analyzed by CBCT. RESULTS: Of the 300 mandibular first premolars, 197 (65.7%) had one root with one canal (1R1C), 49 (16.3%) had one root with two canals (1R2C), 51 (17.0%) had two roots with one canal in each root (2R2C), and three (1.0%) had three roots with one canal in each root (3R3C). Statistical analyses showed that women had a significantly higher incidence of 1R1C mandibular first premolars (71.4%) than men (58.8%, p = 0.031), and men had a significantly higher incidence of 2R2C mandibular first premolars (27.2%) than women (8.5%, p < 0.001). One hundred and twenty-two (81.3%) of the 150 patients had a symmetrical root and root canal system between the right and left mandibular first premolars. Men had a significantly higher symmetrical rate of 2R2C mandibular first premolars (26.5%) than women (8.2%, p = 0.013). CONCLUSION: Approximately 82% of mandibular first premolars in northern Taiwanese patients have one root with either one or two canals. There are significant differences in the number of roots and canals and symmetry of the root canal system of bilateral mandibular first premolars between male and female northern Taiwanese patients.