Consideration of hereditary effects in the radiological protection system: evolution and current status.

PURPOSE: The purpose of this paper is to provide an overview of the methodology used to estimate radiation genetic risks and quantify the risk of hereditary effects as outlined in the ICRP Publication 103. It aims to highlight the historical background and development of the doubling dose method for estimating radiation-related genetic risks and its continued use in radiological protection frameworks. RESULTS: This article emphasizes the complexity associated with quantifying the risk of hereditary effects caused by radiation exposure and highlights the need for further clarification and explanation of the calculation method. As scientific knowledge in radiation sciences and human genetics continues to advance in relation to a number of factors including stability of disease frequency, selection pressures, and epigenetic changes, the characterization and quantification of genetic effects still remains a major issue for the radiological protection system of the International Commission on Radiological Protection. CONCLUSION: Further research and advancements in this field are crucial for enhancing our understanding and addressing the complexities involved in assessing and managing the risks associated with hereditary effects of radiation.

Eurados review of retrospective dosimetry techniques for internal exposures to ionising radiation and their applications.

This work presents an overview of the applications of retrospective dosimetry techniques in case of incorporation of radionuclides. The fact that internal exposures are characterized by a spatially inhomogeneous irradiation of the body, which is potentially prolonged over large periods and variable over time, is particularly problematic for biological and electron paramagnetic resonance (EPR) dosimetry methods when compared with external exposures. The paper gives initially specific information about internal dosimetry methods, the most common cytogenetic techniques used in biological dosimetry and EPR dosimetry applied to tooth enamel. Based on real-case scenarios, dose estimates obtained from bioassay data as well as with biological and/or EPR dosimetry are compared and critically discussed. In most of the scenarios presented, concomitant external exposures were responsible for the greater portion of the received dose. As no assay is available which can discriminate between radiation of different types and different LETs on the basis of the type of damage induced, it is not possible to infer from these studies specific conclusions valid for incorporated radionuclides alone. The biological dosimetry assays and EPR techniques proved to be most applicable in cases when the radionuclides are almost homogeneously distributed in the body. No compelling evidence was obtained in other cases of extremely inhomogeneous distribution. Retrospective dosimetry needs to be optimized and further developed in order to be able to deal with real exposure cases, where a mixture of both external and internal exposures will be encountered most of the times.

EURADOS work on internal dosimetry.

European Radiation Dosimetry Group (EURADOS) Working Group 7 is a network on internal dosimetry that brings together researchers from more than 60 institutions in 21 countries. The work of the group is organised into task groups that focus on different aspects, such as development and implementation of biokinetic models (e.g. for diethylenetriamine penta-acetic acid decorporation therapy), individual monitoring and the dose assessment process, Monte Carlo simulations for internal dosimetry, uncertainties in internal dosimetry, and internal microdosimetry. Several intercomparison exercises and training courses have been organised. The IDEAS guidelines, which describe - based on the International Commission on Radiological Protection's (ICRP) biokinetic models and dose coefficients - a structured approach to the assessment of internal doses from monitoring data, are maintained and updated by the group. In addition, Technical Recommendations for Monitoring Individuals for Occupational Intakes of Radionuclides have been elaborated on behalf of the European Commission, DG-ENER (TECHREC Project, 2014-2016, coordinated by EURADOS). Quality assurance of the ICRP biokinetic models by calculation of retention and excretion functions for different scenarios has been performed and feedback was provided to ICRP. An uncertainty study of the recent caesium biokinetic model quantified the overall uncertainties, and identified the sensitive parameters of the model. A report with guidance on the application of ICRP biokinetic models and dose coefficients is being drafted at present. These and other examples of the group's activities, which complement the work of ICRP, are presented.

ICRP Publication 134: Occupational Intakes of Radionuclides: Part 2.

Abstract ­: The 2007 Recommendations of the International Commission on Radiological Protection (ICRP, 2007) introduced changes that affect the calculation of effective dose, and implied a revision of the dose coefficients for internal exposure, published previously in the Publication 30 series (ICRP, 1979, 1980, 1981, 1988b) and Publication 68 (ICRP, 1994b). In addition, new data are available that support an update of the radionuclide-specific information given in Publications 54 and 78 (ICRP, 1988a, 1997b) for the design of monitoring programmes and retrospective assessment of occupational internal doses. Provision of new biokinetic models, dose coefficients, monitoring methods, and bioassay data was performed by Committee 2, Task Group 21 on Internal Dosimetry, and Task Group 4 on Dose Calculations. A new series, the Occupational Intakes of Radionuclides (OIR) series, will replace the Publication 30 series and Publications 54, 68, and 78. Part 1 of the OIR series has been issued (ICRP, 2015), and describes the assessment of internal occupational exposure to radionuclides, biokinetic and dosimetric models, methods of individual and workplace monitoring, and general aspects of retrospective dose assessment. The following publications in the OIR series (Parts 2­5) will provide data on individual elements and their radioisotopes, including information on chemical forms encountered in the workplace; a list of principal radioisotopes and their physical half-lives and decay modes; the parameter values of the reference biokinetic model; and data on monitoring techniques for the radioisotopes encountered most commonly in workplaces. Reviews of data on inhalation, ingestion, and systemic biokinetics are also provided for most of the elements. Dosimetric data provided in the printed publications of the OIR series include tables of committed effective dose per intake (Sv per Bq intake) for inhalation and ingestion, tables of committed effective dose per content (Sv per Bq measurement) for inhalation, and graphs of retention and excretion data per Bq intake for inhalation. These data are provided for all absorption types and for the most common isotope(s) of each element. The electronic annex that accompanies the OIR series of reports contains a comprehensive set of committed effective and equivalent dose coefficients, committed effective dose per content functions, and reference bioassay functions. Data are provided for inhalation, ingestion, and direct input to blood. The present publication provides the above data for the following elements: hydrogen (H), carbon (C), phosphorus (P), sulphur (S), calcium (Ca), iron (Fe), cobalt (Co), zinc (Zn), strontium (Sr), yttrium (Y), zirconium (Zr), niobium (Nb), molybdenum (Mo), and technetium (Tc).

TECHNICAL RECOMMENDATIONS FOR MONITORING INDIVIDUALS FOR OCCUPATIONAL INTAKES OF RADIONUCLIDES.

The TECHREC project, funded by the European Commission, will provide Technical Recommendations for Monitoring Individuals for Occupational Intakes of Radionuclides It is expected that the document will be published by the European Commission as a report in its Radiation Protection Series during 2016. The project is coordinated by the European Radiation Dosimetry Group (EURADOS) and is being carried out by members of EURADOS Working Group 7 (Internal Dosimetry). This paper describes the aims and purpose of the Technical Recommendations, and explains how the project is organised.

EURADOS-IDEAS GUIDELINES (VERSION 2) FOR THE ESTIMATION OF COMMITTED DOSES FROM INCORPORATION MONITORING DATA.

Dose assessment after intakes of radionuclides requires application of biokinetic and dosimetric models and assumptions about factors influencing the final result. In 2006, a document giving guidance for such assessment was published, commonly referred to as the IDEAS Guidelines. Following its publication, a working group within the European networks CONRAD and EURADOS was established to improve and update the IDEAS Guidelines. This work resulted in Version 2 of the IDEAS Guidelines, which was published in 2013 in the form of a EURADOS report. The general structure of the original document was maintained; however, new procedures were included, e.g. the direct dose assessment method for (3)H or special procedure for wound cases applying the NCRP wound model. In addition, information was updated and expanded, e.g. data on dietary excretion of U, Th, Ra and Po for urine and faeces or typical and achievable values for detection limits for different bioassay measurement techniques.

Radiation Dose to Patients from Radiopharmaceuticals: a Compendium of Current Information Related to Frequently Used Substances.

This report provides a compendium of current information relating to radiation dose to patients, including biokinetic models, biokinetic data, dose coefficients for organ and tissue absorbed doses, and effective dose for major radiopharmaceuticals based on the radiation protection guidance given in Publication 60(ICRP, 1991). These data were mainly compiled from Publications 53, 80, and 106(ICRP, 1987, 1998, 2008), and related amendments and corrections. This report also includes new information for 82Rb-chloride, iodide (123I, 124I, 125I, and 131I) and 123I labeled 2ß-carbomethoxy 3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FPCIT).The coefficients tabulated in this publication will be superseded in due course by values calculated using new International Commission on Radiation Units and Measurements/International Commission on Radiological Protection adult and paediatric reference phantoms and Publication 103 methodology (ICRP,2007). The data presented in this report are intended for diagnostic nuclear medicine and not for therapeutic applications.

A biokinetic model for systemic technetium in adult humans.

This paper reviews biokinetic data for technetium and proposes a biokinetic model for systemic technetium in adult humans. The development of parameter values focuses on data for pertechnetate TcO(-)(4) the most commonly encountered form of technetium and the form expected to be present in body fluids. The model is intended as a default model for occupational or environmental intake of technetium, i.e. applicable in the absence of form- or site-specific information. Tissues depicted explicitly in the model include thyroid, salivary glands, stomach wall, right colon wall, liver, kidneys, and bone. Compared with the ICRP's current biokinetic model for occupational or environmental intake of technetium (ICRP 1993, 1994), the proposed model provides a more detailed and biologically realistic description of the systemic behaviour of technetium and is based on a broader set of experimental and medical data. For acute input of (99m)Tc (T(1/2) = 6.02 h) to blood, the ratios of cumulative (time-integrated) activity predicted by the current ICRP model to that predicted by the proposed model range from 0.4-7 for systemic regions addressed explicitly in both models. For acute input of (99)Tc (T(1/2) = 2.1 × 10(5) year) to blood, the corresponding ratios range from 0.2-30.

Multiple state transport deduced by weak antilocalization and electron-electron interaction effects in Sb(x)Te(1-x) layers.

Quantum corrections to the conductivity due to the weak antilocalization (WAL) and electron-electron interaction (EEI) effects are investigated in Sb-Te layers to evaluate the number of independent conduction channels in the topological insulator system. We separate the two contributions in the logarithmic temperature dependence of conductivity relying on their distinct response to a magnetic field. For the WAL effect, the amplitude parameter α being -1 observed in magnetoconductivity is confirmed. The magnitude of the EEI contribution is too large to be produced by one transport channel. The mixing between the surface and bulk states is thus indicated to be weak in the Sb-Te system. In addition, the disorder scattering appears to be less influential for the EEI effect than for the WAL effect.

Transport properties in a Sb-Te binary topological-insulator system.

Sb-Te layers having various compositions between Sb2Te3 and Sb2Te are grown using molecular beam epitaxy. The structural and electrical properties of the layers change gradually with composition but exhibit a discontinuity involving a bistability. The holes in the layers are generated by Sb bilayers intercalated between Sb2Te3 quintuple layers and their mobility is governed by the scattering from the parent acceptors. Magnetoresistance for compositions around SbTe is linear, for which the reduction of the parabolic component due to low mobility is crucial. Density functional calculations predict Sb2Te3 and SbTe to be topological insulators (TIs) resembling Bi2Se3 and Bi2Te3, respectively. The prefactor of the weak antilocalization effect is α =- 1 regardless of the composition. The Sb-Te system is thus a family of TIs possessing undisturbed surface states for which the location of the Dirac point with respect to the bulk band gap is adjustable.

Post-deposition annealing of praseodymia films on Si(111) at low temperatures.

Thin heteroepitaxial praseodymia films with fluorite structure on Si(111) were annealed under ultra-high vacuum conditions at temperatures in the region of 100 up to 300 °C. Afterward investigations by x-ray diffraction, grazing incidence x-ray diffraction and x-ray reflectometry were performed to obtain information about structural changes of the film during the annealing process. For this reason, praseodymia Bragg peaks were carefully analyzed within the kinematic diffraction theory. This analysis demonstrates the coexistence of different praseodymia phases depending on the conditions of preparation. Here, annealing of the samples up to 150 °C leads to a homogeneous film with a PrO(1.833) phase and with negligible strain since both the lateral and vertical lattice parameters nearly match the corresponding bulk praseodymia phase. Further annealing leads to oxygen loss accompanied by significantly increased lattice parameters. Since the lateral lattice parameter is pinned at the interface, the vertical lattice constant has to increase considerably due to the tetragonal distortion of the film. This causes the decomposition of the film into two oxide species with significantly different oxygen contents. Annealing at 300 °C reduces the film almost completely to PrO(1.5) which has the minimum content of oxygen.

EURADOS coordinated action on research, quality assurance and training of internal dose assessments.

EURADOS working group on 'Internal Dosimetry (WG7)' represents a frame to develop activities in the field of internal exposures as coordinated actions on quality assurance (QA), research and training. The main tasks to carry out are the update of the IDEAS Guidelines as a reference document for the internal dosimetry community, the implementation and QA of new ICRP biokinetic models, the assessment of uncertainties related to internal dosimetry models and their application, the development of physiology-based models for biokinetics of radionuclides, stable isotope studies, biokinetic modelling of diethylene triamine pentaacetic acid decorporation therapy and Monte-Carlo applications to in vivo assessment of intakes. The working group is entirely supported by EURADOS; links are established with institutions such as IAEA, US Transuranium and Uranium Registries (USA) and CEA (France) for joint collaboration actions.

New developments in internal dosimetry models.

This paper describes new biokinetic and dosimetric models, especially those being developed by ICRP which will be used in the forthcoming documents on Occupational Intakes of Radionuclides. It also presents the results of a working group within the European project CONRAD which is being continued within EURADOS. This group is implementing the new models, performing quality assurance of the model implementation (including their description) and giving guidance to the scientific community on the application of the models for individual dose assessment.

Minimising activity and dose with enhanced image quality by radiopharmaceutical administrations.

Owing to the introduction of new diagnostic procedures, such as computed tomography (CT), positron emission tomography (PET) and single photon emission computed tomography (SPECT), the individual dose caused by medical exposures has grown rapidly in the last years. This is especially a subject to radiation protection for nuclear medical diagnosis, since in this case radiopharmaceuticals are administered to the patient, meaning not only a radiation exposure to the diseased tissue but also to the healthy tissues of large parts of the body. 'Minimizing Activity and Dose with Enhanced Image quality by Radiopharmaceutical Administrations' (MADEIRA) is a project cofunded by the European Commission within the Seventh Euratom Framework Programme that aims to improve three-dimensional (3D) nuclear medical imaging technologies significantly. MADEIRA is aiming to improve the efficacy and safety of 3D PET and SPECT functional imaging by optimising the spatial resolution and the signal-to-noise ratio, improving the knowledge of the temporal variation of the radiopharmaceuticals' uptake in and clearance from tumourous and healthy tissues, and evaluation of the corresponding patient dose. Using an optimised imaging procedure that improves the information gained per unit administered dose, MADEIRA aims especially to reduce the dose to healthy tissues of the patient. In this paper, an overall summary of the current achievements will be presented.

Investigation of biokinetics of radioiodine with a population kinetics approach.

The dosimetric studies required for planning individually tailored radioiodine therapy of benign thyroid pathologies may be too complex and time-demanding for many ordinary nuclear medicine departments. In this work, a preliminary population kinetics approach was applied to a model structure for iodine biokinetics in order to identify those model features that actually need to be individually investigated, in order to simplify the protocol for data collection in patients. Data from 29 patients undergoing radioiodine therapy for the treatment of the autonomous nodule syndrome were used in the analysis. The greatest inter-individual variations were observed in the parameters describing the transformation of iodide into organic iodine in the thyroid and in the kinetics of the organic form.

New calculations for internal dosimetry of beta-emitting radiopharmaceuticals.

The calculation of absorbed dose from internally incorporated radionuclides is based on the so-called specific absorbed fractions (SAFs) which represent the fraction of energy emitted in a given source region that is absorbed per unit mass in a specific target organ. Until recently, photon SAFs were calculated using MIRD-type mathematical phantoms. For electrons, the energy released was assumed to be absorbed locally ('ICRP 30 approach'). For this work, photon and electron SAFs were derived with Monte Carlo simulations in the new male voxel-based reference computational phantom adopted by the ICRP and ICRU. The present results show that the assumption of electrons being locally absorbed is not always true at energies above 300-500 keV. For source/target organ pairs in close vicinity, high-energy electrons escaping from the source organ may result in cross-fire electron SAFs in the same order of magnitude as those from photons. Examples of organ absorbed doses per unit activity are given for (18)F-choline and (123)I-iodide. The impact of the new electron SAFs used for absorbed dose calculations compared with the previously used assumptions was found to be small. The organ dose coefficients for the two approaches differ by not more than 6 % for most organs. Only for irradiation of the urinary bladder wall by activity in the contents, the ICRP 30 approach presents an overestimation of approximately 40-50%.

Pancreatic ductal abnormalities documented by secretin-enhanced MRCP in asymptomatic subjects with chronic pancreatic hyperenzymemia.

OBJECTIVES: Persistently high serum pancreatic enzymes in asymptomatic subjects are considered a benign idiopathic condition called "non-pathological chronic pancreatic hyperenzymemia" (CPH). However, recent studies with advanced imaging techniques have brought to light abnormal pancreatic findings in a significant proportion of these subjects. The objective of this study was to evaluate pancreatic ductal morphology by secretin-enhanced magnetic resonance cholangiopancreatography (MRCP-S) in subjects with CPH and compare MRCP imaging before and after secretin injection. METHODS: In total, 25 consecutive patients with CPH were investigated by MRCP and MRCP-S and compared with 28 consecutive age-matched controls with recurrent upper abdominal pain and normal pancreatic enzymemia. RESULTS: MRCP-S showed abnormal pancreatic morphological findings in 13 of the 25 CPH cases (52%) and 1/28 controls (3.6%) (P<0.001). MRCP findings consistent with a diagnosis of chronic pancreatitis, according to the Cambridge classification, were detected in eight CPH cases (32%) after secretin injection but none of the controls. Secretin stimulation boosted the diagnostic yield of MRCP for the diagnosis of chronic pancreatitis fourfold. Pancreas divisum was identified in two CPH cases and one control. A 15-min persisting dilation of the main pancreatic duct was noted in three cases in each group. Compared with MRCP, MRCP-S showed significantly fewer CPH patients with normal findings (P<0.02). CONCLUSIONS: MRCP-S detected ductal findings consistent with chronic pancreatitis in one-third of CPH cases. Pancreas divisum and some dysfunction at the level of Vater's papilla were reported in 8 and 12% of the patients, respectively. MRCP-S is to be recommended, instead of MRCP, in the diagnostic work-up of CPH subjects.

Biokinetic modelling of DTPA decorporation therapy: the CONRAD approach.

Administration of diethylene triamine pentaacetic acid (DTPA) can enhance the urinary excretion rate of plutonium (Pu) for several days, but most of this Pu decorporation occurs on the first day after treatment. The development of a biokinetic model describing the mechanisms of decorporation of actinides by administration of DTPA was initiated as a task of the coordinated network for radiation dosimetry project. The modelling process was started by using the systemic biokinetic model for Pu from Leggett et al. and the biokinetic model for DTPA compounds of International Commission on Radiation Protection Publication 53. The chelation of Pu and DTPA to Pu-DTPA was treated explicitly and is assumed to follow a second-order process. It was assumed that the chelation takes place in the blood and in the rapid turnover soft tissues compartments of the Pu model, and that Pu-DTPA behaves in the same way as administered DTPA. First applications of this draft model showed that the height of the peak of urinary excretion after administration of DTPA was determined by the chelation rate. However, repetitions of DTPA administration shortly after the first one showed no effect in the application of the draft model in contrast to data from real cases. The present draft model is thus not yet realistic. Therefore several questions still have to be answered, notably about where the Pu-DTPA complexes are formed, which biological ligands of Pu are dissociated, if Pu-DTPA is stable and if the biokinetics of Pu-DTPA excretion is similar to that of DTPA. Further detailed studies of human contamination cases and experimental data about Pu-DTPA kinetics will be needed in order to address these issues. The work will now be continued within a working group of EURADOS.

Diagnostic yield of ERCP and secretin-enhanced MRCP and EUS in patients with acute recurrent pancreatitis of unknown aetiology.

BACKGROUND: Magnetic resonance cholangio-pancreatography (MRCP), endoscopic ultrasonography (EUS), and endoscopic cholangio-pancreatography (ERCP) are the most frequently employed second-step procedures to detect biliary and pancreatic abnormalities in patients with acute recurrent pancreatitis (ARP) of unknown aetiology. MRCP and EUS both give a better view of the bilio-pancreatic ductal system after secretin stimulation (MRCP-S, EUS-S). EUS also serves to identify changes in the pancreatic parenchyma consistent with chronic pancreatitis, at an early stage. However, no studies have compared MRCP-S, EUS-S, and ERCP in the diagnosis of recurrent pancreatitis. AIM: To prospectively compare the diagnostic yield of MRCP-S, EUS-S, and ERCP in the evaluation of patients with acute recurrent pancreatitis with non-dilated ducts, of unknown aetiology. METHODS: Forty-four consecutive patients with ARP were prospectively scheduled to undergo MRCP-S, EUS-S and ERCP, in accordance with a standard protocol approved by the institutional review board. Diagnoses such as biliary microlithiasis, congenital variants of the pancreatic ducts, chronic pancreatitis and sphincter of Oddi dysfunction were compared between the three procedures. The diagnosis of chronic pancreatitis was established according to ductal morphology by MRCP-S and ERCP, ductal and parenchymal morphology by EUS-S. RESULTS: The three procedures combined achieved a diagnosis that could have explained the recurrence of pancreatitis in 28/44 patients (63.6%). EUS-S recognized ductal and/or parenchymal abnormalities with the highest frequency (35/44 patients, 79.5%). Both MRCP-S and EUS-S were superior to ERCP for detecting pancreatic ductal abnormalities. EUS-S showed up pancreatic parenchymal changes in more than half the cases. Both EUS and MRCP secretin kinetics were concordant in identifying two cases with sphincter of Oddi dysfunction. CONCLUSIONS: The diagnostic yield of EUS-S in recurrent pancreatitis with non-dilated ducts and unknown aetiology was 13.6% and 16.7% higher than MRCP-S and ERCP respectively (although not significant), which both gave substantially similar diagnostic yields. In no case did ERCP alone find a diagnosis missed by the other two procedures. MRCP-S and EUS-S should both be used in the diagnostic work-up of idiopathic recurrent pancreatitis as complementary, first-line, techniques, instead of ERCP.