Networking in biological and physical retrospective dosimetry in Europe and beyond Open Access

Abstract

INTRODUCTION

The use of ionizing radiation is well documented to be beneficial to society, for example in medicine and industry; however, there is a constant small but non-zero risk of radiation accidents or incidents involving potential exposure to small or large numbers of individuals. The consequences of radiation exposure at higher doses are fairly well understood due to data from various radiation accidents and medical settings [1]. These vary depending on a large number of factors, including exposure circumstances (e.g. whether the whole body or only part of the body is exposed), type of radiation (e.g. gamma or neutron) and dose received. In cases where exposure is suspected, it is important to characterize the exposure as far as possible in order to help define the appropriate medical intervention and also for reassurance purposes for those in the vicinity of the incident but not exposed [2].

Biological dosimetry is well established as a tool to estimate exposure doses and, in some circumstances, to provide information on how the dose was received, e.g. the partial body or acute/protracted nature of the exposure. Tools such as the dicentric assay have evolved over the last 60 years to a point where this assay is incredibly well standardized, with many publications describing the technique and advances, including an International Atomic Energy Agency manual [3] and two International Organization for Standardization, ISO, standards [4, 5]. At the same time, this is a very active field, with new tools and techniques emerging including most recently transcriptional analysis of radiation induced changes to gene expression.

In recent years, a large amount of effort has been focused on networking in biological and physical retrospective dosimetry, in support of preparedness for large-scale radiation emergency response as well as further advancement of the techniques and their potential use in routine exposure circumstances, e.g. in support of personalized radiation medicine [6]. This short manuscript presents the current status of biological and physical retrospective dosimetry with a focus on networking and potential future developments.

BIOLOGICAL AND PHYSICAL RETROSPECTIVE DOSIMETRY

For accidents in in occupational exposure settings, dose assessment is usually based on use of dosimetry badges (e.g. [7]). Where individuals, e.g. members of the public are not wearing badges, if the doses are sufficiently high (>1–2 Gy), clinical signs and symptoms can be used as described in the TMT (Triage, Monitoring and Treatment) Handbook [8]. However, it is possible that individuals can receive doses on the order of a few Gy and not exhibit clinical signs and symptoms, and it is here that retrospective dosimetry – based on assessment of doses in biological materials (e.g. blood or finger nails) or in materials that individuals happen to have been carrying (fortuitous dosimeters, e.g. chip cards and mobile phones) – can really contribute, as well as in the reassurance of those unlikely to have been exposed. In all cases, dosimetry can be supplemented by modelling at the individual or population levels where appropriate. It is usual now for clinical signs and symptoms to be used to identify the most highly exposed, then for retrospective dosimetry to support the secondary phase of triage, sometimes called the ‘rapid response’, as well as later helping to further identify those exposed at lower doses or to help reassure those not exposed [2].

The principles of retrospective dosimetry are very simple – from a population of suspected exposed individuals, biological or physical samples are taken, and the radiation induced signal in these is compared to pre-defined calibration curves, in order to provide information to help form medical intervention. It is important to note here that while retrospective dosimetry is a very important tool, it would be very unusual for these techniques to be used on their own to guide treatment – instead the outputs will be used together with the clinical signs and symptoms and other information to help inform decision making. Dose assessment methods other than retrospective biological and physical retrospective dosimetry are not considered further here.

Retrospective dosimetry started with biological methods in blood, and a large amount is known about the effects of ionizing radiation on cells and tissues, from the initial ionization and excitation, the formation of free radicals and DNA damage signalling and repair, through to formation of chromosome aberrations, mutations and inflammatory response, then to acute and late effects such as dysfunction of individual organs and, usually only after several or many years, radiation-linked cancers [9]. 1 Gy X-irradiation, for example, causes approximately 100 000 ionizations in the cell nucleus, ~35 DNA double strand breaks, and ~0.3 lethal events and 0.1 dicentrics or micronuclei per exposed cell.

The concept of the ideal dosimeter was advanced in order to aid development in this field. In short, it is desirable that any dosimetry technique is specific to radiation/has a very low background in the suspected exposed population, can easily be calibrated at the population level (that there is low variation in response), that sampling and analysis are quick, easy and cheap, that the measurable effect is persistent and that the technique provides information about the long term risk (ideally to the individual) as well as about the dose and exposure circumstances. It is clear that no single ideal dosimeter exists; however, this principle has been well used in biological and physical dosimetry in order to guide development of a suite of tools that complement each other, and which together have at least most of these characteristics ([2, 10] and references therein).

The current status of the toolkit for retrospective dosimetry was most recently described by Wojcik et al. [11], which presented the methods in tabulated format with information about the tissue in which the techniques are applied, the relevant time scales and whether the techniques can be used for protracted and/or non-uniform exposures, the sensitivity (dose range) and specificity to ionizing radiation, whether the technique is appropriate for or has been adapted for use in triage situations (where rapid but uncertain initial dose estimates are used to help separate those definitely exposed from the worried well), and whether the tool has been formally standardized by ISO.

The characteristics of each of the retrospective dosimetry assays have been very well described in the literature but, in brief, the dicentric assay is the ‘gold standard’ as it is radiation specific with very little variation in response between individuals. The micronucleus assay has more background variation but is easier to ‘score’ the aberrations so is the assay of choice for many laboratories. Both of these assays require ~48 hours to culture the blood lymphocytes in order to be able to visualize the aberrations, and premature chromosome condensation has been developed to address this – this technique is technically difficult but can significantly reduce the time for dose estimation from several days to ~1 day. This assay is also useful at doses higher than the ~5 Gy limit for the traditional chromosomal assays (due to cell killing at higher doses). The gamma-H2AX assay has a much lower minimum detectable dose than the traditional assays (~10 mGy compared to ~100 mGy in ‘ideal’ conditions), but as this is based on the cellular DNA damage response, it is only really applicable for blood samples taken up to ~24–48 hours post exposure [12]. Gene expression is the most recently proposed technique, which is still under development, and which relies on radiation induced transcriptional changes in one or more commonly several radiation responsive genes [13].

In addition to these assays in blood, optically stimulated and thermally stimulated luminescence (OSL and TL), and electron spin or paramagnetic resonance (ESR and EPR) can be used to measure the energy from ionizing radiation exposure stored in certain exposed materials, including tooth enamel and fingernails for EPR and electronic components and the mineral glass used in smartphones for TL/OSL [14, 15].

NETWORKING IN EUROPE AND BEYOND

Many laboratories around the world now exist and have expertise in one or many of these tools. At the UK Health Security Agency, for example, the laboratory was established in 1968 and in 2024, the scientists are internationally recognized as experts in this field, with expertise and experience in the dicentric, micronucleus, premature chromosome condensation, fluorescence in situ hybridization, gamma-H2AX and gene expression assays, as well as the optically stimulated luminescence physical dosimetry method. Recent advances in the field have focused on automation of many of the assays, to increase capacity and capability. For large-scale radiation emergency response, however, the problem remains that individual laboratories tend to be highly specialized and thus have only a few trained individuals able to carry out the assays. The favoured solution to this problem has been for the international community to come together in formal or informal networks to together establish joint procedures for large-scale response. This work started in Europe over 30 years ago and today there are a number of very well-established mutual response networks operating in the field of biological and physical retrospective dosimetry.

In Europe, the most well-established network is RENEB – Running the European Network of Biological and retrospective Physical dosimetry [2]. RENEB was founded within the 7th EU framework EURATOM Fission Programme and now consists of 26 organizations from 16 European countries who have signed a Memorandum of Understanding for mutual assistance in large-scale radiological and nuclear emergencies. RENEB aims to provide consistent, high quality dose assessment with capacity for assessment of between several hundred to several thousand doses assessed per week depending on the nature of the incident. The network meets regularly to ensure the mutual capacity and capability is maintained and expanded where possible, including through incorporation of new techniques, as well as to promote quality assurance, to identify emerging challenges and to ensure effective communication and dissemination of the available expertise and techniques within the emergency response community. Further information on the available tools and techniques can be found here: www.reneb.net.

The European Radiation Dosimetry Network (EURADOS; www.eurados.org) Working Group 10 on retrospective dosimetry also supports networking in this field with a focus on multiparametric dose assessment (how the techniques can be used together to provide a fuller picture of the dose and exposure circumstances). The group also works together to develop and evaluate new methods, and to establish common approaches to uncertainty estimation and the calculations associated with partial body and internal exposures (e.g. [16]). EURADOS and RENEB have worked together on a large number of recent initiatives, including the interlaboratory comparison and field test 2017 [17], which has resulted in publications about the use of the dicentric assay [18] and gene expression [13] as well as the reference dosimetry in this realistic non-uniform exposure scenario [10].

At the worldwide level, the World Health Organisation, WHO, BioDoseNet (www.who.int/groups/biodosenet) is leading in terms of provision of networking opportunities for existing, new and emerging laboratories. As with the other networks, the overarching aim of BioDoseNet is to support management and decision-making in large radiation emergency events where the capability of any one individual laboratory is likely to be overwhelmed [19]. The network meets approximately every 2 years, usually at the EPRBioDose Meetings organized by the International Association for Biological and EPR Radiation Dosimetry (iaberd.org).

DISCUSSION AND CONCLUSIONS

Retrospective dosimetry in support of a large-scale radiation accident or incident is a well established in terms of the available tools and techniques and the complementary nature of these in terms of provision of information about the dose and also the exposure circumstances. In addition to continued development of new techniques, much recent development has been focused on networking in support of emergency response, and this has resulted in robust, highly quality assured systems of mutual aid, including through the RENEB network. It is essential that collaboration here continues to expand, through the worldwide networks such as WHO BioDoseNet but also through further development of local and regional networks.

The continued integration of new and emerging techniques such as new omics technologies, use of radiation specific changes in mRNA and AI/machine learning will help to ensure that retrospective dosimetry remains fit for purpose (e.g. in support of space tourism). Wider applications of the methods, e.g. for development of personalized radiation medicine, continue to support development for emergency response purposes also [6].

Networking supports joint development of tools to further assist harmonization and quality assurance in retrospective dosimetry (e.g. [20]). Networks also actively support and encourage the participation and training of early career scientists, something which is essential for the sustainability of retrospective dosimetry worldwide.

In conclusion, networking in physical and retrospective dosimetry continues to progress (e.g. [21]), something which is highly desirable in the context of ensuring readiness for the entire community to support each other in response to a large-scale radiation emergency.

ACKNOWLEDGEMENTS

The author acknowledges the collaborative contributions to development of this field of all her colleagues in the various networks mentioned herein, without whom this work would not have been possible.

CONFLICT OF INTEREST

The author declares no conflict of interest.

FUNDING

The author of this work has been partly supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Chemical & Radiation Threats & Hazards, a partnership between UKHSA and Imperial College London. The views expressed are those of the authors and not necessarily those of the NIHR, UKHSA or the Department of Health and Social Care.

This manuscript has been prepared following the conference presentation given by E. A. Ainsbury at the 7th International Symposium of the Network-type, Joint Usage/Research Center for Radiation, Disaster Medical Science, Radiation Medicine from the Perspective of Radiation Disaster, Medical Science Research, Hiroshima University, in February 2023.

REFERENCES