Joint EURADOS-EANM initiative for an advanced computational framework for the assessment of external dose rates from nuclear medicine patients.

BACKGROUND: In order to ensure adequate radiation protection of critical groups such as staff, caregivers and the general public coming into proximity of nuclear medicine (NM) patients, it is necessary to consider the impact of the radiation emitted by the patients during their stay at the hospital or after leaving the hospital. Current risk assessments are based on ambient dose rate measurements in a single position at a specified distance from the patient and carried out at several time points after administration of the radiopharmaceutical to estimate the whole-body retention. The limitations of such an approach are addressed in this study by developing and validating a more advanced computational dosimetry approach using Monte Carlo (MC) simulations in combination with flexible and realistic computational phantoms and time activity distribution curves from reference biokinetic models. RESULTS: Measurements of the ambient dose rate equivalent H*(10) at 1 m from the NM patient have been successfully compared against MC simulations with 5 different codes using the ICRP adult reference computational voxel phantoms, for typical clinical procedures with 99mTc-HDP/MDP, 18FDG and Na131I. All measurement data fall in the 95% confidence intervals, determined for the average simulated results. Moreover, the different MC codes (MCNP-X, PHITS, GATE, GEANT4, TRIPOLI-4®) have been compared for a more realistic scenario where the effective dose rate E of an exposed individual was determined in positions facing and aside the patient model at 30 cm, 50 cm and 100 cm. The variation between codes was lower than 8% for all the radiopharmaceuticals at 1 m, and varied from 5 to 16% for the face-to face and side-by-side configuration at 30 cm and 50 cm. A sensitivity study on the influence of patient model morphology demonstrated that the relative standard deviation of H*(10) at 1 m for the range of included patient models remained under 16% for time points up to 120 min post administration. CONCLUSIONS: The validated computational approach will be further used for the evaluation of effective dose rates per unit administered activity for a variety of close-contact configurations and a range of radiopharmaceuticals as part of risk assessment studies. Together with the choice of appropriate dose constraints this would facilitate the setting of release criteria and patient restrictions.

Very high-energy electron therapy as light-particle alternative to transmission proton FLASH therapy - An evaluation of dosimetric performances.

PURPOSE: Clinical translation of FLASH-radiotherapy (RT) to deep-seated tumours is still a technological challenge. One proposed solution consists of using ultra-high dose rate transmission proton (TP) beams of about 200-250 MeV to irradiate the tumour with the flat entrance of the proton depth-dose profile. This work evaluates the dosimetric performance of very high-energy electron (VHEE)-based RT (50-250 MeV) as a potential alternative to TP-based RT for the clinical transfer of the FLASH effect. METHODS: Basic physics characteristics of VHEE and TP beams were compared utilizing Monte Carlo simulations in water. A VHEE-enabled research treatment planning system was used to evaluate the plan quality achievable with VHEE beams of different energies, compared to 250 MeV TP beams for a glioblastoma, an oesophagus, and a prostate cancer case. RESULTS: Like TP, VHEE above 100 MeV can treat targets with roughly flat (within ± 20 %) depth-dose distributions. The achievable dosimetric target conformity and adjacent organs-at-risk (OAR) sparing is consequently driven for both modalities by their lateral beam penumbrae. Electron beams of 400[500] MeV match the penumbra of 200[250] MeV TP beams and penumbra is increased for lower electron energies. For the investigated patient cases, VHEE plans with energies of 150 MeV and above achieved a dosimetric plan quality comparable to that of 250 MeV TP plans. For the glioblastoma and the oesophagus case, although having a decreased conformity, even 100 MeV VHEE plans provided a similar target coverage and OAR sparing compared to TP. CONCLUSIONS: VHEE-based FLASH-RT using sufficiently high beam energies may provide a lighter-particle alternative to TP-based FLASH-RT with comparable dosimetric plan quality.

More May Not be Better: Enhanced Spacecraft Shielding May Exacerbate Cognitive Decrements by Increasing Pion Exposures during Deep Space Exploration.

The pervasiveness of deep space radiation remains a confounding factor for the transit of humans through our solar system. Spacecraft shielding both protects astronauts but also contributes to absorbed dose through galactic cosmic ray interactions that produce secondary particles. The resultant biological effects drop to a minimum for aluminum shielding around 20 g/cm2 but increase with additional shielding. The present work evaluates for the first time, the impact of secondary pions on central nervous system functionality. The fractional pion dose emanating from thicker shielded spacecraft regions could contribute up to 10% of the total absorbed radiation dose. New results from the Paul Scherrer Institute have revealed that low dose exposures to 150 MeV positive and negative pions, akin to a Mars mission, result in significant, long-lasting cognitive impairments. These surprising findings emphasize the need to carefully evaluate shielding configurations to optimize safe exposure limits for astronauts during deep space travel.

Activity standardisation of 177Lu.

177Lu decays through low-energy ß-- and γ-emissions in addition to conversion and Auger electrons. To support the use of this radiopharmaceutical in Switzerland, a 177Lu solution was standardised using the ß-γ coincidence technique, as well as the TDCR method. The solution had no 177mLu impurity. Primary coincidence measurements, with plastic scintillators for beta detection, were carried out using both analogue and digital electronics. TDCR measurements using only defocusing were also made. Monte Carlo calculations were used to compute the detection efficiency. The coincidence measurements with both analogue and digital electronics are compatible within one standard uncertainty, but they are lower than (and discrepant with) the TDCR measurements. An ampoule of this solution was submitted to the BIPM as a contribution to the Système International de Référence.

3D-conformal very-high energy electron therapy as candidate modality for FLASH-RT: A treatment planning study for glioblastoma and lung cancer.

BACKGROUND: Pre-clinical ultra-high dose rate (UHDR) electron irradiations on time scales of 100 ms have demonstrated a remarkable sparing of brain and lung tissues while retaining tumor efficacy when compared to conventional dose rate irradiations. While clinically-used gantries and intensity modulation techniques are too slow to match such time scales, novel very-high energy electron (VHEE, 50-250 MeV) radiotherapy (RT) devices using 3D-conformed broad VHEE beams are designed to deliver UHDR treatments that fulfill these timing requirements. PURPOSE: To assess the dosimetric plan quality obtained using VHEE-based 3D-conformal RT (3D-CRT) for treatments of glioblastoma and lung cancer patients and compare the resulting treatment plans to those delivered by standard-of-care intensity modulated photon RT (IMRT) techniques. METHODS: Seven glioblastoma patients and seven lung cancer patients were planned with VHEE-based 3D-CRT using 3 to 16 coplanar beams with equidistant angular spacing and energies of 100 and 200 MeV using a forward planning approach. Dose distributions, dose-volume histograms, coverage (V95% ) and homogeneity (HI98% ) for the planning target volume (PTV), as well as near-maximum doses (D2% ) and mean doses (Dmean ) for organs-at-risk (OAR) were evaluated and compared to clinical IMRT plans. RESULTS: Mean differences of V95% and HI98% of all VHEE plans were within 2% or better of the IMRT reference plans. Glioblastoma plan dose metrics obtained with VHEE configurations of 200 MeV and 3-16 beams were either not significantly different or were significantly improved compared to the clinical IMRT reference plans. All OAR plan dose metrics evaluated for VHEE plans created using 5 beams of 100 MeV were either not significantly different or within 3% on average, except for Dmean for the body, Dmean for the brain, D2% for the brain stem, and D2% for the chiasm, which were significantly increased by 1, 2, 6, and 8 Gy, respectively (however below clinical constraints). Similarly, the dose metrics for lung cancer patients were also either not significantly different or were significantly improved compared to the reference plans for VHEE configurations with 200 MeV and 5 to 16 beams with the exception of D2% and Dmean to the spinal canal (however below clinical constraints). For the lung cancer cases, the VHEE configurations using 100 MeV or only 3 beams resulted in significantly worse dose metrics for some OAR. Differences in dose metrics were, however, strongly patient-specific and similar for some patient cases. CONCLUSIONS: VHEE-based 3D-CRT may deliver conformal treatments to simple, mostly convex target shapes in the brain and the thorax with a limited number of critical adjacent OAR using a limited number of beams (as low as 3 to 7). Using such treatment techniques, a dosimetric plan quality comparable to that of standard-of-care IMRT can be achieved. Hence, from a treatment planning perspective, 3D-conformal UHDR VHEE treatments delivered on time scales of 100 ms represent a promising candidate technique for the clinical transfer of the FLASH effect.

The general-purpose Geant4 Monte Carlo toolkit and its Geant4-DNA extension to investigate mechanisms underlying the FLASH effect in radiotherapy: Current status and challenges.

FLASH radiotherapy is a promising approach to cancer treatment that offers several advantages over conventional radiotherapy. With this novel technique, high doses of radiation are delivered in a short period of time, inducing the so-called FLASH effect - a phenomenon characterized by healthy tissue sparing without alteration of tumor control. The mechanisms behind the FLASH effect remain unknown. One way to approach this problem is to gain insight into the initial parameters that can distinguish FLASH from conventional irradiation by simulating particle transport in aqueous media using the general-purpose Geant4 Monte Carlo toolkit and its Geant4-DNA extension. This review article discusses the current status of Geant4 and Geant4-DNA simulations to investigate mechanisms underlying the FLASH effect, as well as the challenges faced in this research field. One of the primary challenges is to accurately simulate the experimental irradiation parameters. Another challenge is the temporal extension of the simulations. This review also focuses on two hypotheses to explain the FLASH effect - namely the oxygen depletion hypothesis and the inter-track interactions hypothesis - and discusses how the Geant4 toolkit can be used to investigate them. The aim of this review is to provide an overview of Geant4 and Geant4-DNA simulations for FLASH radiotherapy and to highlight the challenges that need to be overcome in order to better study the FLASH effect.

Dosimetry in the lungs of α-particles (210Po) and ß-particles (210Pb) present in the tobacco smoke of conventional cigarettes and heated tobacco products.

Tobacco products contain radioactive 210Pb and 210Po which can be transferred from the filler to the mainstream smoke. When inhaled, they can contribute to the radioactive dose to the lungs and are suspected to significantly contribute to lung cancer from smoking. Currently, no data are available on the radioactive risk of the heated tobacco products (HTP). However, due to the relatively high heat involved in some of these devices, there are concerns about the volatility of polonium particles. Here we used data on the 210Po and 210Pb content in tobacco smoke along with biokinetic and dosimetric models to compute the effective dose induced by conventional smoking and by using an HTP device (PMI IQOS system). Results show that conventional smoking of one pack per day induces a dose to the lung of about 0.3 mSv/year. This dose decreases by a factor of ten (0.03 mSv/year) for the IQOS system. However, this dose reduction is not obtained by specific countermeasures but by the fact that the IQOS system heats only 15% of the tobacco filler to the target temperature of 330 °C. When heated homogeneously to 300 °C, both conventional and Heets (IQOS) cigarettes release about 80% of the 210Po from the tobacco, leading to similar doses to lungs.

Modeling of scavenging systems in water radiolysis with Geant4-DNA.

PURPOSE: This paper presents the capabilities of the Geant4-DNA Monte Carlo toolkit to simulate water radiolysis with scavengers using the step-by-step (SBS) or the independent reaction times (IRT) methods. It features two examples of application areas: (1) computing the escape yield of H2O2 following a 60Co γ-irradiation and (2) computing the oxygen depletion in water irradiated with 1 MeV electrons. METHODS: To ease the implementation of the chemical stage in Geant4-DNA, we developed a user interface that helps define the chemical reactions and set the concentration of scavengers. The first application area example required two computational steps to perform water radiolysis using NO2- and NO3- as scavengers and a 60Co irradiation. The oxygen depletion computation technique for the second application area example consisted of simulating track segments of 1 MeV electrons and determining the radio-induced loss and gain of oxygen molecules. RESULTS: The production of H2O2 under variable scavenging levels is consistent with the literature; the mean relative difference between the SBS and IRT methods is 7.2 % ± 0.5 %. For the oxygen depletion 1 µs post-irradiation, the mean relative difference between both methods is equal to 9.8 % ± 0.3 %. The results in the microsecond scale depend on the initial partial pressure of oxygen in water. In addition, the computed oxygen depletions agree well with the literature. CONCLUSIONS: The Geant4-DNA toolkit makes it possible to simulate water radiolysis in the presence of scavengers. This feature offers perspectives in radiobiology, with the possibility of simulating cell-relevant scavenging mechanisms.

Geant4-DNA Modeling of Water Radiolysis beyond the Microsecond: An On-Lattice Stochastic Approach.

In this work, we use the next sub-volume method (NSM) to investigate the possibility of using the compartment-based ("on-lattice") model to simulate water radiolysis. We, first, start with a brief description of the reaction-diffusion master equation (RDME) in a spatially discretized simulation volume ("mesh"), which is divided into sub-volumes (or "voxels"). We then discuss the choice of voxel size and merging technique of a given mesh, along with the evolution of the system using the hierarchical algorithm for the RDME ("hRDME"). Since the compartment-based model cannot describe high concentration species of early radiation-induced spurs, we propose a combination of the particle-based step-by-step ("SBS") Brownian dynamics model and the compartment-based model ("SBS-RDME model") for the simulation. We, finally, use the particle-based SBS Brownian dynamics model of Geant4-DNA as a reference to test the model implementation through several benchmarks. We find that the compartment-based model can efficiently simulate the system with a large number of species and for longer timescales, beyond the microsecond, with a reasonable computing time. Our aim in developing this model is to study the production and evolution of reactive oxygen species generated under irradiation with different dose rate conditions, such as in FLASH and conventional radiotherapy.

Activity standardisation of 223Ra.

We report here on the primary activity standardisation of a223Ra dichloride solution in equilibrium with its decay daughters. Both the triple-to-double-coincidence-ratio (TDCR) method with an in-house TDCR detector and the CIEMAT-NIST efficiency tracing (CNET) technique with a commercial counter were used. The liquid scintillation efficiencies for both methods are about 6 while the activities they predict with about 0.4% relative standard uncertainty agree within 0.15%. For backup, the solution was also standardised with 4πγ NaI(Tl) integral counting with a well-type NaI(Tl) detector, and efficiencies computed by Monte Carlo simulations using the GEANT code. This simple technique, unused previously for this nuclide, yielded an activity concentration compatible with, but 1% lower than, the one determined by liquid scintillation counting.

A benchmarking study of Geant4 for Auger electrons emitted by medical radioisotopes.

Auger emitting radioisotopes are of great interest in targeted radiotherapy because, once internalised in the tumour cells, they can deliver dose locally to the radiation sensitive targets, while not affecting surrounding cells. Geant4 is a Monte Carlo code widely used to characterise the physics mechanism at the basis of targeted radiotherapy. In this work, we benchmarked the modelling of the emission of Auger electrons in Geant4 deriving from the decay of 123I, 124I, 125I radionuclides against existing theoretical approaches. We also compared Geant4 against reference data in the case of 131Cs, which is of interest for brachytherapy. In the case of 125I and 131Cs, the simulation results are compared to experimental measurements as well. Good agreement was found between Geant4 and the reference data. As far as we know, this is the first study aimed to benchmark against experimental measurements the emission of Auger electrons in Geant4 for radiotherapy applications.

Determination of the gamma and X-ray emission intensities of terbium-161.

In this study, the gamma and X-ray emission intensities of 161Tb were determined using a high-purity germanium spectrometer. The samples used were previously standardised by coincidence counting and Triple to Double Coincidence Ratio (TDCR) methods. A total of 28 gamma-rays and 4 X-rays were measured and compared with previous measurements performed more than 30 years ago. Most of the lines are in agreement, while large discrepancies are observed for 5 lines. The uncertainties have been dramatically decreased with respect to previous measurements giving a better knowledge of the 161 Tb day.

Efficiency of the RADPAD Surgical Cap in Reducing Brain Exposure During Pacemaker and Defibrillator Implantation.

OBJECTIVES: This study sought to investigate the RADPAD No Brainer (Worldwide Innovation and Technologies, Overland Park, Kansas) efficiency in reducing brain exposure to scattered radiation. BACKGROUND: Cranial radioprotective caps such as the RADPAD No Brainer are being marketed as devices that significantly reduce operator's brain exposure to scattered radiation. However, the efficiency of the RADPAD No Brainer in reducing brain exposure in clinical practice remains unknown to date. METHODS: Five electrophysiologists performing device implantations over a 2-month period wore the RADPAD cap with 2 strips of 11 thermoluminescent dosimeter pellets covering the front head above and under the shielded cap. Phantom measurements and Monte Carlo simulations were performed to further investigate brain dose distribution. RESULTS: Our study showed that the right half of the operators' front head was the most exposed region during left subpectoral device implantation; the RADPAD cap attenuated the skin front-head exposure but provided no protection to the brain. The exposure of the anterior part of the brain was decreased by a factor of 4.5 compared with the front-head skin value thanks to the skull. The RADPAD cap worn as a protruding horizontal plane, however, reduced brain exposure by a factor of 1.7 (interquartile range: 1.3 to 1.9). CONCLUSIONS: During device implantation, the RADPAD No Brainer decreased the skin front head exposure but had no impact on brain dose distribution. The RADPAD No Brainer worn as a horizontal plane worn around the neck reduces brain exposure and confirms that the exposure comes from upward scattered radiation.

Activity standardisation of 161Tb.

161Tb, which emits low-energy ß-- and γ-particles in addition to conversion and Auger electrons, has aroused increased interest for medical imaging and therapy. To support the use of this radionuclide, a161Tb solution was standardised using the ß-γ coincidence technique, as well as the TDCR method. The solution had 4.5·10-3% of 160Tb impurities. Primary coincidence measurements, with plastic or liquid scintillators for beta detection, were carried out using both analogue and digital electronics. TDCR measurements using defocusing, grey filtering and quenching for varying the efficiency were also made. Monte Carlo calculations were used to compute the detection efficiency. The coincidence measurements with analogue electronics and the TDCR show a good consistency, and are compatible with the digital coincidence results within uncertainties. An ampoule of this solution was submitted to the BIPM as a contribution to the international reference system.

Dosimetric and preparation procedures for irradiating biological models with pulsed electron beam at ultra-high dose-rate.

PURPOSE: Preclinical studies using a new treatment modality called FLASH Radiotherapy (FLASH-RT) need a two-phase procedure to ensure minimal uncertainties in the delivered dose. The first phase requires a new investigation of the reference dosimetry lying outside the conventional metrology framework from national metrology institutes but necessary to obtain traceability, repeatability, and stability of irradiations. The second consists of performing special quality assurance procedure prior to irradiation. MATERIALS AND METHODS: The Oriatron eRT6 (PMB-Alcen, France) is an experimental high dose-per-pulse linear accelerator, delivering a 6 MeV pulsed electron beam with mean dose-rates, ranging from a few Gy/min up to thousands of Gy/s. Absolute dosimetry is investigated with alanine, thermo-luminescent dosimeters (TLD) and radiochromic films as well as an ionization chamber for relative stability. The beam characteristic and dosimetry are prepared for three different setups. RESULTS: A cross-check between alanine, films and TLD revealed a dose agreement within 3% for dose-rates between 0.078 Gy/s and 1050 Gy/s, showing that these dosimeters are suitable for absolute dosimetry for FLASH-RT. In absence of appropriate setup dependent corrections, active dosimetry can reveal dose deviations up to 15% of the prescribed dose. These differences reduce to less than 3% when our dosimetric procedure is applied. CONCLUSION: We developed procedures to accurately irradiate biological models. Our method is based on validated absolute dosimeters and extends their use to routine FLASH irradiations. We reached an agreement of 3% between the delivered and prescribed dose and developed the requirements needed for workflows of preclinical and clinical studies.

Model of ambient dose equivalent for radium contamination: Dependence on the geometry of the source.

Industrial activities involving radium sources, such as watchmaking, were still common up until the 1960s. They produced contaminations in building materials and the soil in a large variety of geometries. The potential remediation of such places requires instruments that are properly calibrated as well as adequate procedures. We have developed a model that estimates the rate of ambient dose equivalent H˙∗(10) at 10 cm and 1 m from a source of 226Ra and its progeny in both the soil or the building materials. Our model, described here, uses Monte Carlo (GEANT4) computed yield functions of H˙∗(10) per unit activity induced by point-like sources in different contaminated materials. Fit functions of the yield curve of H˙∗(10) are provided for outdoor contamination. The model can be used for any geometrical activity distribution and we present an example showing the dependency of H˙∗(10) on the diameter and the depth profile of the sources, for both outdoor and indoor contamination.

Dose assessment following an overexposure of a worker at a Swiss nuclear power plant.

AIM: The aim of this work was to assess the doses received by a diver exposed to a radiation source during maintenance work in the fuel transfer pool at a Swiss nuclear power plant, and to define whether the statutory limit was breached or not. METHOD: Onsite measurements were carried out and different scenarios were simulated using the MicroShield Software and the MCNPX Monte Carlo radiation transport code to estimate the activity of the irradiating object as well as the doses to the limbs and the effective dose delivered to the operator. RESULTS: The activity of the object was estimated to 1.8 TBq. From the various dose estimations, a conservative value of 7.5 Sv was proposed for the equivalent dose to the skin on the hands and an effective dose of 28 mSv. CONCLUSION: The use of different experimental and calculation methods allowed us to accurately estimate the activity of the object and the dose delivered to the diver, useful information for making a decision on the most appropriate scheme of follow up for the patient.