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The present study reports on investigations that we have performed to allow the calculation of effective doses (E) in interventional radiology. The use of published conversion tables might not allow sufficient guidance for the establishment of optimization strategies for procedures in interventional radiology. With the Monte Carlo N-Particle transport code (MCNP4B), conversion coefficients, linking dose-area product (DAP) measurements with E, are calculated for angiography of the lower limbs in six hospitals. The influence of various parameters on the calculation of these conversion coefficients is studied in a systematic way using the 2(n) factorial design. In this design the effect of different parameters and their pair-wise interactions on a certain variable is explored. In our study, the relevant parameters are tube potential, total filtration and field size and position. We concluded that the influence of radiation spectrum (kVp + filtration) is large and that the effect of field position and size is moderate, except when differences are observed in respect of the gonads. In that case, the variation in conversion coefficients is large. The results of this statistical analysis are then applied to the differences observed between the conversion coefficients, calculated for angiography of the lower limbs in the six hospitals. Recommendations for optimization of patient doses are given. [ABSTRACT FROM AUTHOR]

The European epidemiological study EURALOC aimed to establish a dose response relationship for low dose radiation induced eye lens opacities using interventional cardiologists as the study group. Within the EURALOC project, two dosimetry methodologies were developed serving as the basis for cumulative eye lens dose assessment. Besides being the cornerstone of the epidemiological part of the project, these dosimetry methodologies were also used to develop two calculation tools, ‘mEyeDose’ and ‘mEyeDose_X’ which enable to track, calculate, optimise and analyse eye lens doses in interventional cardiology. mEyeDose was developed as a Mobile Web App and serves as a readily accessible, highly didactic educational tool for interventional cardiologists whereas the user-friendly desktop application mEyeDose_X is designed for radiation protection professionals. Both tools are freely available and can be used for a wide range of purposes such as optimisation of working practices, calculation of cumulative eye lens doses or risk assessment prior to routine eye lens dose monitoring. [ABSTRACT FROM AUTHOR]

The first validation results of the two approaches developed in the ELDO project for retrospective assessment of eye lens doses for interventional cardiologists (ICs) are presented in this paper. The first approach (a) is based on both the readings from the routine whole body dosimeter worn above the lead apron and procedure-dependent conversion coefficients, while the second approach (b) is based on detailed information related to the occupational exposure history of the ICs declared in a questionnaire and eye lens dose records obtained from the relevant literature. The latter approach makes use of various published eye lens doses per procedure as well as the appropriate correction factors which account for the use of radiation protective tools designed to protect the eye lens. To validate both methodologies, comprehensive measurements were performed in several Polish clinics among recruited physicians. Two dosimeters measuring whole body and eye lens doses were worn by every physician for at least two months. The estimated cumulative eye lens doses, calculated from both approaches, were then compared against the measured eye lens dose value for every physician separately. Both approaches results in comparable estimates of eye lens doses and tend to overestimate rather than underestimate the eye lens doses. The measured and estimated doses do not differ, on average, by a factor higher than 2.0 in 85% and 62% of the cases used to validate approach (a) and (b), respectively. In specific cases, however, the estimated doses differ from the measured ones by as much as a factor of 2.7 and 5.1 for method (a) and (b), respectively. As such, the two approaches can be considered accurate when retrospectively estimating the eye lens doses for ICs and will be of great benefit for ongoing epidemiological studies. [ABSTRACT FROM AUTHOR]

MELODI is the European platform dedicated to low-dose radiation risk research. From 7 October through 10 October 2013 the Fifth MELODI Workshop took place in Brussels, Belgium. The workshop offered the opportunity to 221 unique participants originating from 22 countries worldwide to update their knowledge and discuss radiation research issues through 118 oral and 44 poster presentations. In addition, the MELODI 2013 workshop was reaching out to the broader radiation protection community, rather than only the low-dose community, with contributions from the fields of radioecology, emergency and recovery preparedness, and dosimetry. In this review, we summarise the major scientific conclusions of the workshop, which are important to keep the MELODI strategic research agenda up-to-date and which will serve to establish a joint radiation protection research roadmap for the future. [ABSTRACT FROM AUTHOR]

Monte Carlo calculations were used to investigate the efficiency of radiation protection equipment in reducing eye and whole body doses during fluoroscopically guided interventional procedures. Eye lens doses were determined considering different models of eyewear with various shapes, sizes and lead thickness. The origin of scattered radiation reaching the eyes was also assessed to explain the variation in the protection efficiency of the different eyewear models with exposure conditions. The work also investigates the variation of eye and whole body doses with ceiling-suspended shields of various shapes and positioning. For all simulations, a broad spectrum of configurations typical for most interventional procedures was considered. Calculations showed that ‘wrap around’ glasses are the most efficient eyewear models reducing, on average, the dose by 74% and 21% for the left and right eyes respectively. The air gap between the glasses and the eyes was found to be the primary source of scattered radiation reaching the eyes. The ceiling-suspended screens were more efficient when positioned close to the patient’s skin and to the x-ray field. With the use of such shields, the Hp(10) values recorded at the collar, chest and waist level and the Hp(3) values for both eyes were reduced on average by 47%, 37%, 20% and 56% respectively. Finally, simulations proved that beam quality and lead thickness have little influence on eye dose while beam projection, the position and head orientation of the operator as well as the distance between the image detector and the patient are key parameters affecting eye and whole body doses. [ABSTRACT FROM AUTHOR]

Nuclear medicine (NM) professionals are potentially exposed to high doses of ionising radiation, particularly in the skin of the hands. Ring dosimeters are used by the workers to ensure extremity doses are kept below the legal limits. However, ring dosimeters are often susceptible to large uncertainties, so it is difficult to ensure a correct measurement using the traditional occupational monitoring methods. An alternative solution is to calculate the absorbed dose by using Monte Carlo simulations. This method could reduce the uncertainty in dose calculation if the exact positions of the worker and the radiation source are represented in these simulations. In this study we present a set of computer vision and artificial intelligence algorithms that allow us to track the exact position of unshielded syringes and the hands of NM workers. We showcase a possible hardware configuration to acquire the necessary input data for the algorithms. And finally, we assess the tracking confidence of our software. The tracking accuracy achieved for the syringe detection was 57% and for the hand detection 98%., (© 2024 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

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 Ḣ * (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 99m Tc-HDP/MDP, 18 FDG and Na 131 I. 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 Ė 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 Ḣ * (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., (© 2024. The Author(s).)

Background: The use of lutetium-177 ( 177 Lu)-based radiopharmaceuticals in peptide receptor nuclear therapy is increasing, but so is the number of nuclear medicine workers exposed to higher levels of radiation. In recent years, [ 177 Lu]Lu-DOTA-TATE has begun to be widely used for the treatment of neuroendocrine tumours. However, there are few studies evaluating the occupational radiation exposure during its administration, and there are still some challenges that can result in higher doses to the staff, such as a lack of trained personnel or fully standardised procedures. In response, this study aims to provide a comprehensive analysis of occupational doses to the staff involved in the administration of [ 177 Lu]Lu-DOTA-TATE., Results: A total of 32 administrations of [ 177 Lu]Lu-DOTA-TATE (7.4 GBq/session) carried out by a physician and a nurse, were studied. In total, two physicians and four nurses were independently monitored with cumulative (passive) and/or real-time (active) dosemeters. Extremity, eye lens and whole-body doses were evaluated in terms of the dosimetric quantities Hp(0.07), Hp(3) and Hp(10), respectively. It was obtained that lead aprons reduced dose rates and whole-body doses by 71% and 69% for the physicians, respectively, and by 56% and 68% for the nurses. On average, normalised Hp(10) values of 0.65 ± 0.18 µSv/GBq were obtained with active dosimetry, which is generally consistent with passive dosemeters. For physicians, the median of the maximum normalised Hp(0.07) values was 41.5 µSv/GBq on the non-dominant hand and 45.2 µSv/GBq on the dominant hand. For nurses 15.4 µSv/GBq on the non-dominant and 13.9 µSv/GBq on the dominant hand. The ratio or correction factor between the maximum dose measured on the hand and the dose measured on the base of the middle/ring finger of the non-dominant hand resulted in a factor of 5/6 for the physicians and 3/4 for the nurses. Finally, maximum normalised Hp(3) doses resulted in 2.02 µSv/GBq for physicians and 1.76 µSv/GBq for nurses., Conclusions: If appropriate safety measures are taken, the administration of [ 177 Lu]Lu-DOTA-TATE is a safe procedure for workers. However, regular monitoring is recommended to ensure that the annual dose limits are not exceeded., (© 2023. The Author(s).)

Absorbed dose heterogeneity in kidney tissues is an important issue in radiopharmaceutical therapy. The effect of absorbed dose heterogeneity in nephrotoxicity is, however, not fully understood yet, which hampers the implementation of treatment optimization by obscuring the interpretation of clinical response data and the selection of optimal treatment options. Although some dosimetry methods have been developed for kidney dosimetry to the level of microscopic renal substructures, the clinical assessment of the microscopic distribution of radiopharmaceuticals in kidney tissues currently remains a challenge. This restricts the anatomical resolution of clinical dosimetry, which hinders a thorough clinical investigation of the impact of absorbed dose heterogeneity. The potential of absorbed dose-response modelling to support individual treatment optimization in radiopharmaceutical therapy is recognized and gaining attraction. However, biophysical modelling is currently underexplored for the kidney, where particular modelling challenges arise from the convolution of a complex functional organization of renal tissues with the function-mediated dose distribution of radiopharmaceuticals. This article reviews and discusses the heterogeneity of absorbed dose distribution in kidney tissues and the absorbed dose-response modelling of nephrotoxicity in radiopharmaceutical therapy. The review focuses mainly on the peptide receptor radionuclide therapy with beta-particle emitting somatostatin analogues, for which the scientific literature reflects over two decades of clinical experience. Additionally, detailed research perspectives are proposed to address various identified challenges to progress in this field., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Objective . The lateral dose fall-off in proton pencil beam scanning (PBS) technique remains the preferred choice for sparing adjacent organs at risk as opposed to the distal edge due to the proton range uncertainties and potentially high relative biological effectiveness. However, because of the substantial spot size along with the scattering in the air and in the patient, the lateral penumbra in PBS can be degraded. Combining PBS with an aperture can result in a sharper dose fall-off, particularly for shallow targets. Approach . The aim of this work was to characterize the radiation fields produced by collimated and uncollimated 100 and 140 MeV proton beams, using Monte Carlo simulations and measurements with a MiniPIX-Timepix detector. The dose and the linear energy transfer (LET) were then coupled with published in silico biophysical models to elucidate the potential biological effects of collimated and uncollimated fields. Main results . Combining an aperture with PBS reduced the absorbed dose in the lateral fall-off and out-of-field by 60%. However, the results also showed that the absolute frequency-averaged LET (LET F ) values increased by a maximum of 3.5 keV μ m -1 in collimated relative to uncollimated fields, while the dose-averaged LET (LET D ) increased by a maximum of 7 keV μ m -1 . Despite the higher LET values produced by collimated fields, the predicted DNA damage yields remained lower, owing to the large dose reduction. Significance . This work demonstrated the dosimetric advantages of combining an aperture with PBS coupled with lower DNA damage induction. A methodology for calculating dose in water derived from measurements with a silicon-based detector was also presented. This work is the first to demonstrate experimentally the increase in LET caused by combining PBS with aperture, and to assess the potential DNA damage which is the initial step in the cascade of events leading to the majority of radiation-induced biological effects., (© 2023 Institute of Physics and Engineering in Medicine.)

Suborgan absorbed dose estimates in mouse kidneys are crucial to support preclinical nephrotoxicity analyses of α- and β-particle-emitting radioligands exhibiting a heterogeneous activity distribution in the kidneys. This is, however, limited by the scarcity of reference dose factors (S values) available in the literature for specific mouse kidney tissues. Methods: A computational multiregion model of a mouse kidney based on high-resolution MRI data from a healthy mouse kidney was developed. The model was used to calculate S values for 5 kidney tissues (cortex, outer and inner stripes of outer medulla, inner medulla, and papilla and pelvis) for a wide range of β- or α-emitting radionuclides (45 in total) of interest for radiopharmaceutical therapy, using Monte Carlo calculations. Additionally, regional S values were applied for a 131 I-labeled single-domain antibody fragment with predominant retention in the outer stripe of the renal outer medulla. Results: The heterogeneous activity distribution in kidneys of considered α- and low- to medium-energy β-emitters considerably affected the absorbed dose estimation in specific suborgan regions. The suborgan tissue doses resulting from the nonuniform distribution of the 131 I-labeled antibody fragment largely deviated (from -40% to 57%) from the mean kidney dose resulting from an assumed uniform activity distribution throughout the whole kidney. The absorbed dose in the renal outer stripe was about 2.0 times higher than in the cortex and in the inner stripe and about 2.6 times higher than in inner tissues. Conclusion: The use of kidney regional S values allows a more realistic estimation of the absorbed dose in different renal tissues from therapeutic radioligands with a heterogeneous uptake in the kidneys. This constitutes an improvement from the simplistic (less accurate) renal dose estimates assuming a uniform distribution of activity throughout kidney tissues. Such improvement in dosimetry is expected to support preclinical studies essential for a better understanding of nephrotoxicity in humans. The dosimetric database has added value in the development of new molecular vectors for radiopharmaceutical therapy., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

The International Commission on Radiation Units and Measurements (ICRU) proposed a new set of operational quantities for radiation protection for external radiation in its Report Committee 26 ( ICRU 95 ). The new proposal aims to improve the coherence between the operational quantities and the definitions of the protection quantities in the recommendations of the International Commission on Radiological Protection set out in 2007 ( Ann. ICRP 37 ). It is expected that this change in operational quantities will impact current dosimeter designs. Although for many photon energies, the conversion coefficients from physical field quantities to the new operational quantities will change relatively little, for radiation fields with low energy photon components, such as medical x-ray applications, there will be a significant decrease in the values of the conversion coefficients. This means that the numerical values of the new operational quantities will be much lower for the same radiation field. These values will be closer to the effective dose, but this change can still cause confusion for medical staff. It is important to examine the effect of the new set of dose conversion coefficients on the personal dose in realistic radiation fields. We performed a study to assess the effect of changing the definition of the operational quantity, personal dose equivalent (Hp), in realistic radiation fields in interventional radiology (IR) workplaces. The x-ray tube kilovoltage peak (kVp) in IR ranges between 60 and 120 kV. The medical staff is exposed to the scattered photons which have a wide range of energies depending on the beam configuration and the patient size. The objective of this study is to 'quantitatively' estimate the impact of implementing the new ICRU quantities of Report 95 in IR radiation fields using Monte Carlo simulations. Simulations of 560 different configurations in IR were performed using MCNPX to calculate fluence binned per energy and angle of incidence.HpandHp(10)were then calculated for each configuration using dose conversion coefficients from fluence given by ICRU Reports 95 and 57, respectively. The results show that the mean of the ratio,Hp(10)/Hp, is 1.6 for all simulated scenarios. This reduction will correct the current overestimation of the effective dose and should result in better compliance with the dose limits in IR. However, it may also have negative consequences on the safety culture among the medical staff. Special care will be needed when interpreting these lower doses., (© 2023 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

Background: Since it was first approved in Europe in 2016, the gallium-68 ( 68 Ga) radiopharmaceutical [ 68 Ga]Ga-DOTA-TOC has been widely used for imaging of somatostatin receptor (SSTR) positive tumours using positron emission tomography-computed tomography (PET/CT). Significant patient benefits have been reported, so its use is rapidly increasing. However, few studies have been published regarding occupational doses to nuclear medicine personnel handling this radiopharmaceutical, despite its manual usage at low distances from the skin and the beta-emission decay scheme, which may result in an increased absorbed dose to their hands. In this context, this study aims to analyse the occupational exposure during the administration of [ 68 Ga]Ga-DOTA-TOC for PET/CT imaging. For this purpose, extremity, eye lens and whole-body dosimetry in terms of Hp(0.07), Hp(3) and Hp(10), respectively, was conducted on six workers with both thermoluminescent dosimeters, and personal electronic dosimeters., Results: The non-dominant hand is more exposed to radiation than the dominant hand, with the thumb and the index fingertip being the most exposed sites on this hand. Qualitative analysis showed that when no shielding is used during injection, doses increase significantly more in the dominant than in the non-dominant hand, so the use of shielding is strongly recommended. While wrist dosimeters may significantly underestimate doses to the hands, placing a ring dosimeter at the base of the ring or middle finger of the non-dominant hand may give a valuable estimation of maximum doses to the hands if at least a correction factor of 5 is applied. Personal equivalent doses for the eyes did not result in measurable values (i.e., above the lowest detection limit) for almost all workers. The extrapolated annual dose estimations showed that there is compliance with the annual dose limits during management of [ 68 Ga]Ga-DOTA-TOC for diagnostics with PET in the hospital included in this study., Conclusions: Imaging with [ 68 Ga]Ga-DOTA-TOC is a safe process for the workers performing the administration of the radiopharmaceutical, including intravenous injection to the patient and the pre- and post-activity control, as it is highly unlikely that annual dose limits will be exceeded if good working practices and shielding are used., (© 2022. The Author(s).)

Background: Quantification of actinium-225 through gamma counter measurements, when there is no secular equilibrium between actinium-225 and its gamma emitting daughters bismuth-213 and/or francium-221, can provide valuable information regarding the possible relocation of recoiled daughters such that related radiotoxicity effects can be evaluated. This study proposes a multiple time-point protocol using the bismuth-213 photopeak with measurements before secular equilibrium between actinium-225 and bismuth-213, and a single time-point protocol using both the francium-221 and bismuth-213 photopeak while assuming secular equilibrium between actinium-225 and francium-221 but not between bismuth-213 and actinium-225., Results: Good agreement (i.e. 3% accuracy) was obtained when relying on a multiple time-points measurement of bismuth-213 to quantify both actinium-225 and excess of bismuth-213. Following scatter correction, actinium-225 can be accurately quantified using the francium-221 in a single time-point measurement within 3% of accuracy. The analysis performed on the stability data of [ 225 Ac]Ac-DEPA and [ 225 Ac]Ac-DOTA complexes, before secular equilibrium between bismuth-213 and actinium-225 was formed, revealed considerable amounts of unbound bismuth-213 (i.e. more than 90%) after 24 h of the radiolabeling most likely due to the recoiled daughter effect., Conclusion: Both protocols were able to accurately estimate 225 Ac-activities provided the francium-221 energy window was corrected for the down scatter of the higher-energy gamma-emissions by bismuth-213. This could prove beneficial to study the recoiled daughter effect and redistribution of free bismuth-213 by monitoring the accumulation or clearance of bismuth-213 in different tissues during biodistribution studies or in patient samples during clinical studies. On the other hand, the single gamma counter measurement protocol, although required a 30 min waiting time, is more time and cost efficient and therefore more appropriate for standardized quality control procedures of 225 Ac-labeled radiopharmaceuticals., (© 2022. The Author(s).)

Targeted radionuclide therapy (TRT) uses radiopharmaceuticals to specifically irradiate tumor cells while sparing healthy tissue. Response to this treatment highly depends on the absorbed dose. Tumor control probability (TCP) models aim to predict the tumor response based on the absorbed dose by taking into account the different characteristics of TRT. For instance, TRT employs radiation with a high linear energy transfer (LET), which results in an increased effectiveness. Furthermore, a heterogeneous radiopharmaceutical distribution could result in a heterogeneous dose distribution at a tissue, cellular as well as subcellular level, which will generally reduce the tumor response. Finally, the dose rate in TRT is protracted, relatively low, and variable over time. This allows cells to repair more DNA damage, which may reduce the effectiveness of TRT. Within this review, an overview is given on how these characteristics can be included in TCP models, while some experimental findings are also discussed. Many parameters in TCP models are preclinically determined and TCP models also play a role in the preclinical stage of radiopharmaceutical development; however, this all depends critically on the calculated absorbed dose. Accordingly, an overview of the existing preclinical dosimetry methods is given, together with their limitation and applications. It can be concluded that although the theoretical extension of TCP models from external beam radiotherapy towards TRT has been established quite well, the experimental confirmation is lacking. Thus, requiring additional comprehensive studies at the sub-cellular, cellular, and organ level, which should be provided with accurate preclinical dosimetry.

This study aimed to evaluate the relationship between the brain absorbed dose and personal dosimetry readings in interventional cardiologists. Interventional procedures were replicated using Monte Carlo simulations (MCNP 6) with anthropomorphic phantoms representing both operator and patient. Absorbed doses were evaluated for 10 predefined regions of the operator's brain as well as for dosemeters at chest and neck level. One beam quality (HVL = 6.2 mm Al) and nine beam projections were considered. A significant bias in the laterality of brain dose was found with doses at the left side of the brain being up to 2.8 times higher compared with the right. The correlation between brain dose and dosemeter reading was found to be dependent on beam projection. Yet, a generalized conversion factor (brain dose normalized by Hp(10)), averaged over all considered beam projections, could be proposed for (retrospective) brain dose estimation from routinely measured dosimetry data., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Clinical dosimetry in molecular radiotherapy (MRT) is a multi-step procedure, prone to uncertainties at every stage of the dosimetric workflow. These are difficult to assess, especially as some are complex or even impossible to measure experimentally. The DosiTest project was initiated to assess the variability associated with clinical dosimetry, by setting up a 'virtual' multicentric clinical dosimetry trial based on Monte Carlo (MC) modelling. A reference patient model with a realistic geometry and activity input for a specific tracer is considered. Reference absorbed dose rate distribution maps are generated at various time-points from MC modelling, combining precise information on density and activity distributions (voxel wise). Then, centre-specific calibration and patient SPECT/CT datasets are modelled, on which the clinical centres can perform clinical (i.e. image-based) dosimetry. The results of this dosimetric analysis can be benchmarked against the reference dosimetry to assess the variability induced by implementing different clinical dosimetry approaches. The feasibility of DosiTest is presented here for a clinical situation of therapeutic administration of 177 Lu-DOTATATE (Lutathera®) peptide receptor radionuclide therapy (PRRT). From a real patient dataset composed of 5 SPECT/CT images and associated calibrations, we generated the reference absorbed dose rate images with GATE. Then, simulated SPECT/CT image generation based on GATE was performed, both for a calibration phantom and virtual patient images. Based on this simulated dataset, image-based dosimetry could be performed, and compared with reference dosimetry. The good agreement, between real and simulated images, and between reference and image-based dosimetry established the proof of concept of DosiTest., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

The aim of this study was to build a simulation framework to evaluate the number of DNA double-strand breaks (DSBs) induced by in vitro targeted radionuclide therapy (TRT). This work represents the first step toward exploring underlying biologic mechanisms and the influence of physical and chemical parameters to enable a better response prediction in patients. We used this tool to characterize early DSB induction by 177 Lu-DOTATATE, a commonly used TRT for neuroendocrine tumors. Methods: A multiscale approach was implemented to simulate the number of DSBs produced over 4 h by the cumulated decays of 177 Lu distributed according to the somatostatin receptor binding. The approach involves 2 sequential simulations performed with Geant4/Geant4-DNA. The radioactive source is sampled according to uptake experiments on the distribution of activities within the medium and the planar cellular cluster, assuming instant and permanent internalization. A phase space is scored around the nucleus of the central cell. Then, the phase space is used to generate particles entering the nucleus containing a multiscale description of the DNA in order to score the number of DSBs per particle source. The final DSB computations are compared with experimental data, measured by immunofluorescent detection of p53-binding protein 1 foci. Results: The probability of electrons reaching the nucleus was significantly influenced by the shape of the cell compartment, causing a large variance in the induction pattern of DSBs. A significant difference was found in the DSBs induced by activity distributions in cell and medium, as is explained by the specific energy ([Formula: see text]) distributions. The average number of simulated DSBs was 14 DSBs per cell (range, 7-24 DSBs per cell), compared with 13 DSBs per cell (range, 2-30 DSBs per cell) experimentally determined. We found a linear correlation between the mean absorbed dose to the nucleus and the number of DSBs per cell: 0.014 DSBs per cell mGy -1 for internalization in the Golgi apparatus and 0.017 DSBs per cell mGy -1 for internalization in the cytoplasm. Conclusion: This simulation tool can lead to a more reliable absorbed-dose-to-DNA correlation and help in prediction of biologic response., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: To model dose-response relationships for in vivo experiments with radiolabelled peptides enabling maximum therapeutic efficacy while limiting toxicity to kidney and bone marrow., Methods: A multiregional murine kidney phantom, with a kinetic model for cortex and outer medulla distribution, were used to predict renal toxicity. Maximum tolerated activities to avoid nephrotoxicity (at 40 Gy Biological Effective Dose BED) and hematologic toxicity (at 2 Gy) were compared. The therapeutic efficacy of 90 Y, 161 Tb, 177 Lu and 213 Bi was assessed at their respective maximum tolerated activities based on cellular-level dosimetry accounting for activity and tumor heterogeneity. These results were compared with average tumor-dosimetry-based predictions., Results: The kidney was found to be the dose-limiting organ for all radionuclides, limiting the administered activity to 44 MBq 177 Lu, 34 MBq 161 Tb, 19 MBq 90 Y and 13 MBq 213 Bi , respectively. The average S-values for the initial heterogeneous activity distribution in the tumor volume are not significantly different from the homogeneous ones. The in vivo tumor cell survivals predicted by assuming uniform dose rate-distributions are not significantly different from those for heterogeneous dose rate-based predictions. The lowest in vivo survival was found for 213 Bi (2%) followed by 161 Tb (30%), 177 Lu (37%) and 90 Y (60%). The minimal effective dose rate for cell kill is 13-14 mGy/h for β-emitters and 2.2 mGy/h for the α-particle emitter 213 Bi, below these values proliferation takes over., Conclusions: Radionuclides emitting α-particles have the highest potential for improving therapeutic efficacy in tumors and metastases with uniform receptor expression, after careful evaluation of their burden to the healthy organs., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Purpose: Monte Carlo modelling of SPECT imaging in Molecular Radiotherapy can improve activity quantification. Until now, SPECT modelling with GATE only considered circular orbit (CO) acquisitions. This cannot reproduce auto-contour acquisitions, where the detector head moves close to the patient to improve image resolution. The aim of this work is to develop and validate an auto-contouring step-and-shoot acquisition mode for GATE SPECT modelling., Methods: 177 Lu and 131 I SPECT experimental acquisitions performed on a Siemens Symbia T2 and GE Discovery 670 gamma camera, respectively, were modelled. SPECT projections were obtained for a cylindrical Jaszczak phantom and a lung and spine phantom. Detector head parameters (radial positions and acquisition angles) were extracted from the experimental projections to model the non-circular orbit (NCO) detector motion. The gamma camera model was validated against the experimental projections obtained with the cylindrical Jaszczak ( 177 Lu) and lung and spine phantom ( 131 I). Then, 177 Lu and 131 I CO and NCO SPECT projections were simulated to validate the impact of explicit NCO modelling on simulated projections., Results: Experimental and simulated SPECT images were compared using the gamma index, and were in good agreement with gamma index passing rate (GIPR) and gamma avg of 96.27%, 0.242 ( 177 Lu) and 92.89%, 0.36 ( 131 I). Then, simulated 177 Lu and 131 I CO and NCO SPECT projections were compared. The GIPR, gamma avg between the two gamma camera motions was 99.85%, 0.108 for 177 Lu and 75.58%, 0.6 for 131 I., Conclusion: This work thereby justifies the need for auto-contouring modelling for isotopes with high septal penetration., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. All rights reserved.)

Background: In order to acquire accurate drug pharmacokinetic information, which is required for tissue dosimetry, micro-SPECT must be quantitative to allow for an accurate assessment of radioligand activity in the relevant tissue. This study investigates the feasibility of deriving accurate mouse-specific time-integrated drug pharmacokinetic data in mouse kidneys from activity measurements using micro-SPECT., Methods: An animal experiment was carried out to evaluate the accuracy of 131 I activity quantification in mouse kidneys (mean tissue volume of 0.140 mL) using a micro-SPECT system against conventional ex vivo gamma counting (GC) in a NaI(Tl) detector. The imaging setting investigated was that of the mouse biodistribution of a 131 I-labelled single-domain antibody fragment (sdAb), currently being investigated for targeted radionuclide therapy of HER2-expressing cancer. SPECT imaging of 131 I 365-keV photons was done with a VECTor/CT system (MILabs, Netherlands) using a high-energy mouse collimator with 1.6-mm-diameter pinholes. For both activity quantification techniques, the pharmacokinetic profile of the radioligand from approximately 1-73 h p.i. was derived and the time-integrated activity coefficient per gram of tissue (ã/M) was estimated. Additionally, SPECT activity recovery coefficients were determined in a phantom setting., Results: SPECT activities underestimate the reference activities by an amount that is dependent on the 131 I activity concentration in the kidney, and thus on the time point of the pharmacokinetic profile. This underestimation is around - 12% at 1.5 h (2.89 MBq mL -1 mean reference activity concentration), - 13% at 6.6 h (149 kBq mL -1 ), - 40% at 24 h (17.6 kBq mL -1 ) and - 46% at 73 h (5.2 kBq mL -1 ) p.i. The ã/M value estimated from SPECT activities is, nevertheless, within - 14% from the reference (GC) ã/M value. Furthermore, better quantitative accuracy (within 2% from GC) in the SPECT ã/M value is achieved when SPECT activities are compensated for partial recovery with a phantom-based recovery coefficient of 0.85., Conclusion: The SPECT imaging system used, together with a robust activity quantification methodology, allows an accurate estimation of time-integrated pharmacokinetic information of the 131 I-labelled sdAb in mouse kidneys. This opens the possibility to perform mouse-specific kidney-tissue dosimetry based on pharmacokinetic data acquired in vivo on the same mice used in nephrotoxicity studies., (© 2022. The Author(s).)

Objective . Treatment planning based on computer simulations wasproposed to account for the increased relative biological effectiveness (RBE) of proton radiotherapy beams near to the edges of the irradiated volume. Since silicon detectors could be used to validate the results of these simulations, it is important to explore the limitations of this comparison. Approach . Microdosimetric measurements with a MicroPlus Bridge V2 silicon detector (thickness = 10 μ m) were performed along the Bragg peak of a clinical proton beam. The lineal energy distributions, the dose-mean values, and the RBE calculated with a biological weighting function were compared with PHITS simulations (microdosimetric target = 1 μ m water sphere), and published clonogenic survival in vitro RBE data for the V79 cell line. The effect of the silicon-to-water conversion was also investigated by comparing three different methodologies (conversion based on a single value, novel bin-to-bin conversions based on SRIM and PSTAR). Main results . Mainly due to differences in the microdosimetric targets, the experimental dose-mean lineal energy and RBE values at the distal edge were respectively up to 53% and 28% lower than the simulated ones. Furthermore, the methodology chosen for the silicon-to-water conversion was proven to affect the dose-mean lineal energy and the RBE 10 up to 32% and 11% respectively. The best methodology to compensate for this underestimation was the bin-to-bin silicon-to-water conversion based on PSTAR. Significance . This work represents the first comparison between PHITS-simulated lineal energy distributions in water targets and corresponding experimental spectra measured with silicon detectors. Furthermore, the effect of the silicon-to-water conversion on the RBE was explored for the first time. The proposed methodology based on the PSTAR bin-to-bin conversion appears to provide superior results with respect to commonly used single scaling factors and is recommended for future studies., (© 2022 Institute of Physics and Engineering in Medicine.)

Our rationale was to build a refined dosimetry model for 177 Lu-DOTATATE in vivo experiments enabling the correlation of absorbed dose with double-strand break (DSB) induction and cell death. Methods: Somatostatin receptor type 2 expression of NCI-H69 xenografted mice, injected with 177 Lu-DOTATATE, was imaged at 0, 2, 5, and 11 d. This expression was used as input to reconstruct realistic 3-dimensional heterogeneous activity distributions and tissue geometries of both cancer and heathy cells. The resulting volumetric absorbed dose rate distributions were calculated using the GATE (Geant4 Application for Tomographic Emission) Monte Carlo code and compared with homogeneous dose rate distributions. The absorbed dose (0-2 d) on micrometer-scale sections was correlated with DSB induction, measured by γH2AX foci. Moreover, the absorbed dose on larger millimeter-scale sections delivered over the whole treatment (0-14 d) was correlated to the modeled in vivo survival to determine the radiosensitivity parameters α and β for comparison with experimental data (cell death assay, volume response) and external-beam radiotherapy. The DNA-damage repair half-life T μ and proliferation doubling time T D were obtained by fitting the DSB and tumor volume data over time. Results: A linear correlation with a slope of 0.0223 DSB/cell mGy -1 between the absorbed dose and the number of DSBs per cell has been established. The heterogeneous dose distributions differed significantly from the homogeneous dose distributions, with their corresponding average S values diverging at 11 d by up to 58%. No significant difference between modeled in vivo survival was observed in the first 5 d when using heterogeneous and uniform dose distributions. The radiosensitivity parameter analysis for the in vivo survival correlation indicated that the minimal effective dose rates for cell kill was 13.72 and 7.40 mGy/h, with an α of 0.14 and 0.264 Gy -1 , respectively, and an α/β of 100 Gy; decreasing the α/β led to a decrease in the minimal effective dose rate for cell kill. Within the linear quadratic model, the best matching in vivo survival correlation (α = 0.1 Gy -1 , α/β = 100 Gy, T μ = 60 h, T D = 14.5 d) indicated a relative biological effectiveness of 0.4 in comparison to external-beam radiotherapy. Conclusion: Our results demonstrated that accurate dosimetric modeling is crucial to establishing dose-response correlations enabling optimization of treatment protocols., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

The purpose of this work is to assess accuracy and compare the performance of radionuclide calibrators (RNCs) used in nuclear medicine departments in Serbia. Testing of the RNCs included verification of measurement accuracy, as well as analysis of routinely used quality control protocols, by using the certified radioactivity standards ( 57 Co, 137 Cs). RNCs performances were assessed with 99m Tc through comparison of reference value for radionuclide activity and RNC measurements. Results of the intercomparison revealed that RNCs, 15 in total, are accurate within 10% in vial geometry and within 15% in syringe geometry. Most of them showed similar performance. The results revealed that container geometry is an important influencing parameter in the accuracy of activity measurement. Obtained results indicate a need for regular calibration and implementation of Quality Control program in order to achieve and maintain the accuracy of activity measurements in nuclear medicine., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

728 simulated microdosimetric lineal energy spectra (26 different ions between 1 H and 238 U, 28 energy points from 1 to 1000 MeV/n) were used in combination with a recently-developed biological weighting function (Parisi et al 2020 Phys. Med. Biol. 1361-6560) and 571 published in vitro clonogenic survival curves in order to: (1) assess prediction intervals for the in silico results by deriving an empirical indication of the experimental uncertainty from the dispersion in the in vitro hamster lung fibroblast (V79) data used for the development of the biophysical model; (2) explore the possibility of modeling the relative biological effectiveness (RBE) of the 10% clonogenic survival of asynchronized normoxic repair-competent mammalian cell lines other than the one used for the development of the model (V79); (3) investigate the predictive power of the model through a comparison between in silico results and in vitro data for 10 ions not used for the development of the model. At first, different strategies for the assessment of the in silico prediction intervals were compared. The possible sources of uncertainty responsible for the dispersion in the in vitro data were also shortly reviewed. Secondly, also because of the relevant scatter in the in vitro data, no statistically-relevant differences were found between the RBE 10 of the investigated different asynchronized normoxic repair-competent mammalian cell lines. The only exception (Chinese Hamster peritoneal fibroblasts, B14FAF28), is likely due to the limited dataset (all in vitro ion data were extracted from a single publication), systematic differences in the linear energy transfer calculations for the employed very-heavy ions, and the use of reference photon survival curves extracted from a different publication. Finally, the in silico predictions for the 10 ions not used for the model development were in good agreement with the corresponding in vitro data., (© 2021 Institute of Physics and Engineering in Medicine.)

Purpose: To assess if single shot acquisitions with solid-state dosimeters as well as Robson's method could replace ionization chambers for tube output and HVL measurements, saving medical physicists time., Material and Methods: The energy responses of 4 solid-state dosimeters with automatic calculation of HVL were compared to ionization chamber measurements. Five anode/filter combinations were tested: Mo/Mo, Mo/Rh, Rh/Rh, W/Rh and W/Ag, from 24kVp to 35kVp. Tube output was measured free in air. HVL was measured using the solid-state dosimeters (single-shot acquisition), then manually with aluminum sheets and finally using the parametrization method of Robson., Results: Deviations in tube output and HVL related to energy response in SSD were small in the 25-32 kVp range, and for tube output typically within 3%. Extrapolation using the Robson parametrization was within 5%, except for one device and for all W/Rh. Deviations of the HVL using the single shot approach were within 10% of the gold standard data. Larger deviations were found at the extreme tube voltages of 24kVp and 35kVp (maximum of 24%)., Conclusion: With the assumption that deviations in tube output of 5% and for HVL of 10% are acceptable, all tested solid state dosimeters met this criterion in the tube voltage range of 26kVp to 32kVp. Robson's method worked well for the spectra for which the method was developed, making both alternative approaches trustworthy for routine quality assurance purposes., (Copyright © 2021 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: Patient-specific dosimetry in MRT relies on quantitative imaging, pharmacokinetic assessment and absorbed dose calculation. The DosiTest project was initiated to evaluate the uncertainties associated with each step of the clinical dosimetry workflow through a virtual multicentric clinical trial. This work presents the generation of simulated clinical SPECT datasets based on GATE Monte Carlo modelling with its corresponding experimental CT image, which can subsequently be processed by commercial image workstations., Methods: This study considers a therapy cycle of 6.85 GBq 177 Lu-labelled DOTATATE derived from an IAEA-Coordinated Research Project (E23005) on "Dosimetry in Radiopharmaceutical therapy for personalised patient treatment". Patient images were acquired on a GE Infinia-Hawkeye 4 gamma camera using a medium energy (ME) collimator. Simulated SPECT projections were generated based on experimental time points and validated against experimental SPECT projections using flattened profiles and gamma index. The simulated projections were then incorporated into the patient SPECT/CT DICOM envelopes for processing and their reconstruction within a commercial image workstation., Results: Gamma index passing rate (2% - 1 pixel criteria) between 95 and 98% and average gamma between 0.28 and 0.35 among different time points revealed high similarity between simulated and experimental images. Image reconstruction of the simulated projections was successful on HERMES and Xeleris workstations, a major step forward for the initiation of a multicentric virtual clinical dosimetry trial based on simulated SPECT/CT images., Conclusions: Realistic 177 Lu patient SPECT projections were generated in GATE. These modelled datasets will be circulated to different clinical departments to perform dosimetry in order to assess the uncertainties in the entire dosimetric chain., (Copyright © 2021. Published by Elsevier Ltd.)

Working Group (WG) 6 'Computational Dosimetry' of the European Radiation Dosimetry Group promotes good practice in the application of computational methods for radiation dosimetry in radiation protection and the medical use of ionising radiation. Its cross-sectional activities within the association cover a large range of current topics in radiation dosimetry, including more fundamental studies of radiation effects in complex systems. In addition, WG 6 also performs scientific research and development as well as knowledge transfer activities, such as training courses. Monte Carlo techniques, including the use of anthropomorphic and other numerical phantoms based on voxelised geometrical models, play a strong part in the activities pursued in WG 6. However, other aspects and techniques, such as neutron spectra unfolding, have an important role as well. A number of intercomparison exercises have been carried out in the past to provide information on the accuracy with which computational methods are applied and whether best practice is being followed. Within the exercises that are still ongoing, the focus has changed towards assessing the uncertainty that can be achieved with these computational methods. Furthermore, the future strategy of WG 6 also includes an extension of the scope toward experimental benchmark activities and evaluation of cross-sections and algorithms, with the vision of establishing a gold standard for Monte Carlo methods used in medical and radiobiological applications., (© 2021 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

In 2011, the International Commission on Radiological Protection (ICRP) recommended reducing the occupational equivalent dose limit for the lens of the eye from 150 mSv/year to 20 mSv/year, averaged over five years, with no single year exceeding 50 mSv. With this recommendation, several important assumptions were made, such as lack of dose rate effect, classification of cataracts as a tissue reaction with a dose threshold at 0.5 Gy, and progression of minor opacities into vision-impairing cataracts. However, although new dose thresholds and occupational dose limits have been set for radiation-induced cataract, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological and mechanistic evidence at doses under 2 Gy. Since the release of the 2011 ICRP statement, the Multidisciplinary European Low Dose Initiative (MELODI) supported in April 2019 a scientific workshop that aimed to review epidemiological, clinical and biological evidence for radiation-induced cataracts. The purpose of this article is to present and discuss recent related epidemiological and clinical studies, ophthalmic examination techniques, biological and mechanistic knowledge, and to identify research gaps, towards the implementation of a research strategy for future studies on radiation-induced lens opacities. The authors recommend particularly to study the effect of ionizing radiation on the lens in the context of the wider, systemic effects, including in the retina, brain and other organs, and as such cataract is recommended to be studied as part of larger scale programs focused on multiple radiation health effects., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: We describe the creation of computational models of lung pathologies indicative of COVID-19 disease. The models are intended for use in virtual clinical trials (VCT) for task-specific optimization of chest x-ray (CXR) imaging. Approach: Images of COVID-19 patients confirmed by computed tomography were used to segment areas of increased attenuation in the lungs, all compatible with ground glass opacities and consolidations. Using a modeling methodology, the segmented pathologies were converted to polygonal meshes and adapted to fit the lungs of a previously developed polygonal mesh thorax phantom. The models were then voxelized with a resolution of 0.5 × 0.5 × 0.5    mm 3 and used as input in a simulation framework to generate radiographic images. Primary projections were generated via ray tracing while the Monte Carlo transport code was used for the scattered radiation. Realistic sharpness and noise characteristics were also simulated, followed by clinical image processing. Example images generated at 120 kVp were used for the validation of the models in a reader study. Additionally, images were uploaded to an Artificial Intelligence (AI) software for the detection of COVID-19. Results: Nine models of COVID-19 associated pathologies were created, covering a range of disease severity. The realism of the models was confirmed by experienced radiologists and by dedicated AI software. Conclusions: A methodology has been developed for the rapid generation of realistic 3D models of a large range of COVID-19 pathologies. The modeling framework can be used as the basis for VCTs for testing detection and triaging of COVID-19 suspected cases., (© 2021 The Authors.)

An improved biological weighting function (IBWF) is proposed to phenomenologically relate microdosimetric lineal energy probability density distributions with the relative biological effectiveness (RBE) for the in vitro clonogenic cell survival (surviving fraction = 10%) of the most commonly used mammalian cell line, i.e. the Chinese hamster lung fibroblasts (V79). The IBWF, intended as a simple and robust tool for a fast RBE assessment to compare different exposure conditions in particle therapy beams, was determined through an iterative global-fitting process aimed to minimize the average relative deviation between RBE calculations and literature in vitro data in case of exposure to various types of ions from 1 H to 238 U. By using a single particle- and energy- independent function, it was possible to establish an univocal correlation between lineal energy and clonogenic cell survival for particles spanning over an unrestricted linear energy transfer range of almost five orders of magnitude (0.2 keV µm -1 to 15 000 keV µm -1 in liquid water). The average deviation between IBWF-derived RBE values and the published in vitro data was ∼14%. The IBWF results were also compared with corresponding calculations (in vitro RBE 10 for the V79 cell line) performed using the modified microdosimetric kinetic model (modified MKM). Furthermore, RBE values computed with the reference biological weighting function (BWF) for the in vivo early intestine tolerance in mice were included for comparison and to further explore potential correlations between the BWF results and the in vitro RBE as reported in previous studies. The results suggest that the modified MKM possess limitations in reproducing the experimental in vitro RBE 10 for the V79 cell line in case of ions heavier than 20 Ne. Furthermore, due to the different modelled endpoint, marked deviations were found between the RBE values assessed using the reference BWF and the IBWF for ions heavier than 2 H. Finally, the IBWF was unchangingly applied to calculate RBE values by processing lineal energy density distributions experimentally measured with eight different microdosimeters in 19 1 H and 12 C beams at ten different facilities (eight clinical and two research ones). Despite the differences between the detectors, irradiation facilities, beam profiles (pristine or spread out Bragg peak), maximum beam energy, beam delivery (passive or active scanning), energy degradation system (water, PMMA, polyamide or low-density polyethylene), the obtained IBWF-based RBE trends were found to be in good agreement with the corresponding ones in case of computer-simulated microdosimetric spectra (average relative deviation equal to 0.8% and 5.7% for 1 H and 12 C ions respectively).

Background and Purpose: There is a continual need for more accurate and effective dosimetric systems for quality assurance (QA) as radiotherapy evolves in complexity. The purpose of this project was to introduce a new system that minimally perturbs the main beam, while assessing its real time 2D dose-rate and field shapes. The system combined reusability, linear dose-rate response, and high spatial and time resolution in a single radiation detection technology that can be applied to surface dose estimation and QA., Materials and Methods: We developed a 2D prototype system consisting of a camera, focusing lenses and short pass filter, placed on the head of a linear accelerator, facing an Al 2 O 3 :C,Mg radioluminescent film. To check the appropriateness of multi-leaf collimator, stability/reproducibility QA tests were prepared using the treatment planning system: including the routinely used alternating leaves, chair and pyramid checks., Results: The Al 2 O 3 :C,Mg film did not perturb the dose vs . depth dose curves determined with a point detector (-0.5% difference). Our results showed a dose-rate linear film response (R 2  = 0.999), from 5 to 600 MU/min. Measured output factors agreed with reference data within ~1%, indicating a potential for small field dosimetry. Both chair and pyramid measured profiles were comparable with those obtained with the treatment planning system within 1%. The alternating leaves test showed an average discrepancy in the valleys of 14%., Conclusions: The prototype demonstrated promising results. It obviated the need for corrections regarding the relative position of the camera, confirming accurate dose-rate delivery and detection of radiation fields., Competing Interests: The whole concept of the ImageDosis system was developed in SCK CEN primarily by dr. Luana de Freitas Nascimento. Dr. Mark Akselrod (Landauer Inc.) is a long-time collaborator, his role was to provide dosimetric materials (and help with questions concerning the dosimetric properties of the material he grows), in special, we asked for micro-crystals, much smaller than the ones Landauer Inc. normally uses in their commercial business. Dr. Akselrod also provided the first films we tested, but the homogeneity of the films had to be improved – again, these films are not commercially available. This is when we reached AGFA (Dr. Leblans), as they have a long experience in coating and printing. They agreed to coat Dr. Akselrod’s micro-crystals for us. All of these happened in a pure collaborative manner and there are absolutely no competing financial or personal interests at play here., (© 2020 The Authors.)

Radiopharmaceutical dosimetry depends on the localization in space and time of radioactive sources and requires the estimation of the amount of energy emitted by the sources deposited within targets. In particular, when computing resources are not accessible, this task can be performed using precomputed tables of specific absorbed fractions (SAFs) or S values based on dosimetric models. The aim of the OpenDose collaboration is to generate and make freely available a range of dosimetric data and tools. Methods: OpenDose brings together resources and expertise from 18 international teams to produce and compare traceable dosimetric data using 6 of the most popular Monte Carlo codes in radiation transport (EGSnrc/EGS++, FLUKA, GATE, Geant4, MCNP/MCNPX, and PENELOPE). SAFs are uploaded, together with their associated statistical uncertainties, in a relational database. S values are then calculated from monoenergetic SAFs on the basis of the radioisotope decay data presented in International Commission on Radiological Protection Publication 107. Results: The OpenDose collaboration produced SAFs for all source region and target combinations of the 2 International Commission on Radiological Protection Publication 110 adult reference models. SAFs computed from the different Monte Carlo codes were in good agreement at all energies, with SDs below individual statistical uncertainties. Calculated S values were in good agreement with OLINDA/EXM 2.0 (commercial) and IDAC-Dose 2.1 (free) software. A dedicated website (www.opendose.org) has been developed to provide easy and open access to all data. Conclusion: The OpenDose website allows the display and downloading of SAFs and the corresponding S values for 1,252 radionuclides. The OpenDose collaboration, open to new research teams, will extend data production to other dosimetric models and implement new free features, such as online dosimetric tools and patient-specific absorbed dose calculation software, together with educational resources., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

This review provides a general overview of the current achievements and challenges in translational dosimetry for targeted alpha therapy (TAT). The concept of targeted radionuclide therapy (TRNT) is described with an overview of its clinical applicability and the added value of TAT is discussed. For TAT, we focused on actinium-225 (225Ac) as an example for alpha particle emitting radionuclides and their features, such as limited range within tissue and high linear energy transfer, which make alpha particle emissions more effective in targeted killing of tumour cells compared to beta radiation. Starting with the state-of-the-art dosimetry for TRNT and TAT, we then describe the challenges that still need to be met in order to move to a personalized dosimetry approach for TAT. Specifically for 225Ac, we discuss the recoiled daughter effect which may provoke significant damage to healthy tissue or organs and should be considered. Next, a broad overview is given of the pre-clinical research on 225Ac-TAT with an extensive description of tools which are only available in a pre-clinical setting and their added value. In addition, we review the preclinical biodistribution and dosimetry studies that have been performed on TAT-agents and more specifically of 225Ac and its multiple progeny, and describe their potential role to better characterize the pharmacokinetic (PK) profile of TAT-agents and to optimize the use of theranostic approaches for dosimetry. Finally, we discuss the support pre-clinical studies may provide in understanding dose-effect relationships, linking radiation dose quantities to biological endpoints and even moving away from macro- to microdosimetry. As such, the translation of pre-clinical findings may provide valuable information and new approaches for improved clinical dosimetry, thus paving the way to personalized TAT.

Purpose: To evaluate image quality of chest radiography for a number of systems in Belgium, using a contrast-detail (c-d) test object and Visual Grading Analysis (VGA) of an anthropomorphic phantom., Methods: The study comprised 22 chest imaging systems in Belgium. C-d data were measured using Leeds TO20 test object, imaged using poly(methyl methacrylate) (PMMA) thicknesses of 9, 13 and 16 cm. Images of the Lungman phantom, with additional tissue-equivalent chest plates to represent different patient sizes, were then acquired. Perceived image quality was evaluated using VGA by three radiologists. Images were acquired at a patient equivalent position with system-specific exposure settings for Posterior-Anterior chest protocol. Incident air kerma (IAK) was measured using a solid-state dosemeter., Results: C-d results showed large differences between the systems. Total number of visible discs ranged from 38 to 83 (for 9 cm PMMA) with a consistent average drop of 10% as PMMA thickness was systematically increased. However, no correlation was found between number of visible discs and IAK. Perceived image quality scored by the readers from the Lungman images decreased with increasing phantom thickness, however no correlation of VGA score with IAK was seen. Moderate correlation was found between the VGA score of one of the readers and the TO20 results, and no correlation for the rest., Conclusions: The spread in dose and image quality measures was high and no correlation was seen between either image quality measure and IAK, suggesting the need for optimization. A more powerful tool is required for task-based optimization in chest radiography., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Background: Survival and linear-quadratic model fitting parameters implemented in treatment planning for targeted radionuclide therapy depend on accurate cellular dosimetry. Therefore, we have built a refined cellular dosimetry model for [ 177 Lu]Lu-DOTA-[Tyr 3 ]octreotate ( 177 Lu-DOTATATE) in vitro experiments, accounting for specific cell morphologies and sub-cellular radioactivity distributions., Methods: Time activity curves were measured and modeled for medium, membrane-bound, and internalized activity fractions over 6 days. Clonogenic survival assays were performed at various added activities (0.1-2.5 MBq/ml). 3D microscopy images (stained for cytoplasm, nucleus, and Golgi) were used as reference for developing polygonal meshes (PM) in 3DsMax to accurately render the cellular and organelle geometry. Absorbed doses to the nucleus per decay (S values) were calculated for 3 cellular morphologies: spheres (MIRDcell), truncated cone-shaped constructive solid geometry (CSG within MCNP6.1), and realistic PM models, using Geant4-10.03. The geometrical set-up of the clonogenic survival assays was modeled, including dynamic changes in proliferation, proximity variations, and cell death. The absorbed dose to the nucleus by the radioactive source cell (self-dose) and surrounding source cells (cross-dose) was calculated applying the MIRD formalism. Finally, the correlation between absorbed dose and survival fraction was fitted using a linear dose-response curve (high α/β or fast sub-lethal damage repair half-life) for different assumptions, related to cellular shape and localization of the internalized fraction of activity., Results: The cross-dose, depending on cell proximity and colony formation, is a minor (15%) contributor to the total absorbed dose. Cellular volume (inverse exponential trend), shape modeling (up to 65%), and internalized source localization (up to + 149% comparing cytoplasm to Golgi) significantly influence the self-dose to nucleus. The absorbed dose delivered to the nucleus during a clonogenic survival assay is 3-fold higher with MIRDcell compared to the polygonal mesh structures. Our cellular dosimetry model indicates that 177 Lu-DOTATATE treatment might be more effective than suggested by average spherical cell dosimetry, predicting a lower absorbed dose for the same cellular survival. Dose-rate effects and heterogeneous dose delivery might account for differences in dose-response compared to x-ray irradiation., Conclusion: Our results demonstrate that modeling of cellular and organelle geometry is crucial to perform accurate in vitro dosimetry.

Changes in the relative biological effectiveness (RBE) of the radiation-induced cell killing of human salivary glands (HSG) were assessed along the Bragg peak of a 60 MeV clinical proton beam by means of coupling biophysical models with the results of Monte Carlo radiation transport simulations and experimental measurements with luminescent detectors. The fluence- and dose-mean unrestricted proton LET were determined along the Bragg peak using a recently developed methodology based on the combination of the response of 7 LiF:Mg,Ti (MTS-7) and 7 LiF:Mg,Cu,P (MCP-7) thermoluminescent detectors. The experimentally assessed LET values were compared with the results of radiation transport simulations using the Monte Carlo code PHITS, showing a good agreement. The cell survival probabilities and RBE were then calculated using the linear-quadratic model with the linear term derived using a phenomenological LET-based model (Carabe A et al 2012 Phys. Med. Biol. 57 1159) in combination with the experimentally-assessed or PHITS-simulated dose mean proton LET values. To the same aim, PHITS simulated microdosimetric spectra were used as input to the modified microdosimetric kinetic model (modified MKM, (Kase et al 2006 Radiat. Res. 166 629-38)). The RBE values calculated with the three aforementioned approaches were compared and found to be in very good agreement between each other, proving that by using dedicated pairs of thermoluminescent detectors it is possible to determine ionization density quantities of therapeutic proton beams which can be applied to predict the local value of the RBE.

For years, the dose limit of 150 mSv for occupational exposure of the lens of the eye to ionising radiation was rarely exceeded, and the dose to the eye was only monitored occasionally. With the national implementation of the European Basic Safety Standards in 2018, this dose limit was reduced to 20 mSv and the Member States are expected to implement an adequate system for the monitoring of category A workers. Where the system for monitoring the whole body dose is settled in most countries, this is not the situation for the lens of the eye. This article presents a system for eye lens dose monitoring, based on the particle type, energy, angle of incidence and geometry of the radiation field and the use of protective measures. The system provides recommendations for the adequate operational quantity and dosemeter position for some of the most relevant workplaces., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)