Risk of Lung Cancer Mortality in Nuclear Workers from Internal Exposure to Alpha Particle-emitting Radionuclides.

BACKGROUND: Carcinogenic risks of internal exposures to alpha-emitters (except radon) are poorly understood. Since exposure to alpha particles-particularly through inhalation-occurs in a range of settings, understanding consequent risks is a public health priority. We aimed to quantify dose-response relationships between lung dose from alpha-emitters and lung cancer in nuclear workers. METHODS: We conducted a case-control study, nested within Belgian, French, and UK cohorts of uranium and plutonium workers. Cases were workers who died from lung cancer; one to three controls were matched to each. Lung doses from alpha-emitters were assessed using bioassay data. We estimated excess odds ratio (OR) of lung cancer per gray (Gy) of lung dose. RESULTS: The study comprised 553 cases and 1,333 controls. Median positive total alpha lung dose was 2.42 mGy (mean: 8.13 mGy; maximum: 316 mGy); for plutonium the median was 1.27 mGy and for uranium 2.17 mGy. Excess OR/Gy (90% confidence interval)-adjusted for external radiation, socioeconomic status, and smoking-was 11 (2.6, 24) for total alpha dose, 50 (17, 106) for plutonium, and 5.3 (-1.9, 18) for uranium. CONCLUSIONS: We found strong evidence for associations between low doses from alpha-emitters and lung cancer risk. The excess OR/Gy was greater for plutonium than uranium, though confidence intervals overlap. Risk estimates were similar to those estimated previously in plutonium workers, and in uranium miners exposed to radon and its progeny. Expressed as risk/equivalent dose in sieverts (Sv), our estimates are somewhat larger than but consistent with those for atomic bomb survivors.See video abstract at, http://links.lww.com/EDE/B232.

Review of chemical and radiotoxicological properties of polonium for internal contamination purposes.

The discovery of polonium (Po) was first published in July, 1898 by P. Curie and M. Curie. It was the first element to be discovered by the radiochemical method. Polonium can be considered as a famous but neglected element: only a few studies of polonium chemistry have been published, mostly between 1950 and 1990. The recent (2006) event in which (210)Po evidently was used as a poison to kill A. Litvinenko has raised new interest in polonium. 2011 being the 100th anniversary of the Marie Curie Nobel Prize in Chemistry, the aim of this review is to look at the several aspects of polonium linked to its chemical properties and its radiotoxicity, including (i) its radiochemistry and interaction with matter; (ii) its main sources and uses; (iii) its physicochemical properties; (iv) its main analytical methods; (v) its background exposure risk in water, food, and other environmental media; (vi) its biokinetics and distribution following inhalation, ingestion, and wound contamination; (vii) its dosimetry; and (viii) treatments available (decorporation) in case of internal contamination.

Toward truly combined PET/CT imaging using PET detectors and photon counting CT with iterative reconstruction implementing physical detector response.

PURPOSE: This paper intends to demonstrate the feasibility of truly combined PET/CT imaging and addresses some of the major challenges raised by this dual modality approach. A method is proposed to retrieve maximum accuracy out of limited resolution computed tomography (CT) scans acquired with positron emission tomography (PET) detectors. METHODS: A PET/CT simulator was built using the LabPET™ detectors and front-end electronics. Acquisitions of energy-binned data sets were made using this low spatial resolution CT system in photon counting mode. To overcome the limitations of the filtered back-projection technique, an iterative reconstruction library was developed and tested for the counting mode CT. Construction of the system matrix is based on a preregistered raster scan from which the experimental detector response is obtained. PET data were obtained sequentially with CT in a conventional manner. RESULTS: A meticulous description of the system geometry and misalignment corrections is imperative and was incorporated into the matrix definition to achieve good image quality. Using this method, no sinogram precorrection or interpolation is necessary and measured projections can be used as raw input data for the iterative reconstruction algorithm. Genuine dual modality PET/CT images of phantoms and animals were obtained for the first time using the same detection platform. CONCLUSIONS: CT and fused PET/CT images show that LabPET™ detectors can be successfully used as individual X-ray photon counting devices for low-dose CT imaging of the anatomy in a molecular PET imaging context.

Treatment of actinide exposures: a review of Ca-DTPA injections inside CEA-COGEMA plants.

Calcium diethylenetriamine pentacetate (Ca-DTPA) has been used for medical treatment of plutonium and americium contaminations in the CEA and COGEMA plants from 1970 to 2003. This paper is a survey of the injections Ca-DTPA administered as a chelating molecule and it will be a part of the authorisation process for Ca-DTPA by intravenous administration. Out of 1158 injections administered to 469 persons, 548 events of possible or confirmed contamination were reported. These employees were followed by occupational physicians according to the current French regulations. These incidents took place at work, were most often minor, not requiring follow-up treatment. The authors present (1) a synthesis of the most recent findings. Due to its short biological half-time and its limited action in the blood, Ca-DTPA does not chelate with plutonium and americium as soon as these elements are deposited in the target organs. It justifies an early treatment, even in cases of suspected contamination followed by additional injections if necessary (2) data concerning these 1158 injections (route of contamination, dosage, adverse effects, etc.) The authors also investigated a study on the efficacy of the product on a group of persons having received five or more injections. These results were compared with the efficacy estimated theoretically. Dosages and therapeutic schemes were proposed based on these observations. This synthesis is the result of a collective work having mobilised the occupational medicine departments, the medical laboratories inside a working group CEA-COGEMA-SPRA.

Reconstruction of Internal Doses for the Alpha-Risk Case-Control Study of Lung Cancer and Leukaemia Among European Nuclear Workers.

The Alpha-Risk study required the reconstruction of doses to lung and red bone marrow for lung cancer and leukaemia cases and their matched controls from cohorts of nuclear workers in the UK, France and Belgium. The dosimetrists and epidemiologists agreed requirements regarding the bioassay data, biokinetic and dosimetric models and dose assessment software to be used and doses to be reported. The best values to use for uncertainties on the monitoring data, setting of exposure regimes and characteristics of the exposure material, including lung solubility, were the responsibility of the dosimetrist responsible for each cohort. Among 1721 subjects, the median absorbed dose to the lung from alpha radiations was 2.1 mGy, with a maximum dose of 316 mGy. The lung doses calculated reflect the higher levels of exposure seen among workers in the early years of the nuclear industry compared to today.

EURADOS intercomparison on emergency radiobioassay.

Nine laboratories participated in an intercomparison exercise organised by the European Radiation Dosimetry Group (EURADOS) for emergency radiobioassay involving four high-risk radionuclides ((239)Pu, (241)Am, (90)Sr and (226)Ra). Diverse methods of analysis were used by the participating laboratories for the in vitro determination of each of the four radionuclides in urine samples. Almost all the methods used are sensitive enough to meet the requirements for emergency radiobioassay derived for this project in reference to the Clinical Decision Guide introduced by the NCRP. Results from most of the methods meet the requirements of ISO 28218 on accuracy in terms of relative bias and relative precision. However, some technical gaps have been identified. For example, some laboratories do not have the ability to assay samples containing (226)Ra, and sample turnaround time would be expected to be much shorter than that reported by many laboratories, as timely results for internal contamination and early decisions on medical intervention are highly desired. Participating laboratories are expected to learn from each other on the methods used to improve the interoperability among these laboratories.

Medical countermeasures after a radiological event: an update from the CATO project.

PURPOSE: As part of the European project 'CBRN crisis management: Architecture, Technologies and Operational Procedures' (CATO), an open Toolbox is in development that will address the needs of all stakeholders from first responders to decision makers. A database on chemical, biological, radiological and nuclear (CBRN) threats, including information on medical countermeasures, will be integrated in this Toolbox. RESULTS AND CONCLUSIONS: After a radiological accident, review of national and international recommendations for the major countermeasures (stable iodine, Prussian Blue, and diethylenetriaminepentaacetic acid [DTPA]) showed that discrepancies in treatment protocols and open questions remain: How to proceed in case of repeated release of radioiodines? Which dosage for Prussian Blue? For which radionuclides is DTPA really effective? This paper brings elements to answer these questions.

Increased retention of americium in kidneys as compared with plutonium in an actinide wound contamination model in the rat.

PURPOSE: Americium-241 ((241)Am) presents a potential risk for nuclear industry workers associated with reactor decommissioning and aging combustible materials. The purpose of this study was to investigate Am renal retention after actinide contamination by wounding in the rat. MATERIALS AND METHODS: Anesthetized rats were contaminated with Mixed Oxide (MOX) (7.1% Plutonium [Pu] by mass and containing 27% Am as % total alpha activity), Pu or Am nitrate following an incision wound of the hind leg. Times of euthanasia ranged from 2 hours to 5 months after contamination. Pu and Am levels were quantified following radiochemistry and alpha-spectrophotometry. RESULTS: Initial data show that over the experimental period the proportion of Am in kidneys as a fraction of total kidney alpha activity was elevated as compared to MOX powder indicating a specific retention in this organ. The percentage of Pu was similar to the powder. After MOX contamination, kidney to liver ratios appeared to increase more markedly for Am (from 0.2 at 7 days to 0.6 at 90 days) as compared with Pu (0.1 at 7 days to 0.2 at 90 days). In accordance with tissue actinide retention the dose from Am to the kidney increases with time. For comparison, the ratio of estimated equivalent doses due to Am to kidney is 1.5-fold greater than for Pu (around 90 versus 60 mSv). CONCLUSION: After actinide contamination of wounds, Am is concentrated in the kidneys as compared to Pu leading to potential exposure of renal tissue to both alpha particles and gamma radiation.

Decontamination of radionuclides from skin: an overview.

The accident in Fukushima has emphasized the need to increase the capacity of health protection for exposed workers, first responders, and the general public in a major accident situation with release of radioactivity. Skin contamination is one of the most probable risks following major nuclear or radiological incidents, but this risk also exists and incidents can happen in industry, research laboratories, or in nuclear medicine departments. The aim of this paper is to provide an overview of the products currently used after skin contamination in order to highlight the needs and ways to improve the medical management of victims. From this review, it can be observed that the current use of these radiological decontamination products is essentially based on empiricism. In addition, some of these products are harsh and irritating, even toxic, possibly damaging the skin barrier. In some emergency situations in which clean water is in short supply, most of the current products cannot be used. Research on the mechanisms of action of decontaminating products is needed to develop a decontamination strategy.

National and international interlaboratories comparisons: a tool for the validation of in vitro and in vivo methods.

The metrological evaluation is indispensable to objectively prove the capability of the medical laboratory to perform analysis. The comparison of analytical performances regarding the accuracy and the reproducibility of the available methods is a real interest of international comparison exercises, especially as the participation to comparison exercises is becoming a requirement for accredited laboratories. Interlaboratory tests are a means of assessing the analytical coherence of medical laboratories. In radiotoxicology, this kind of exercise makes it possible to keep up with laboratory know-how and with the evolution and relative performances of analytical techniques. The objective of this paper will be to present and discuss the main principle of proficiency testing in radiobioassay field illustrated by exercises organised in France for in vivo monitoring and for in vitro analysis.

PROCORAD's proficiency tests as a means of analyzing capacities in emergency situations.

Beyond the metrological evaluation indispensable to prove objectively the capability of a medical laboratory to perform analysis, the comparison of analytical performances regarding the specificity, rapidity and trueness of the available methods is a real interest of international comparison exercises. The objective of this paper is to present and discuss the main results of proficiency testing organized by PROCORAD in the radiobioassay field illustrated by exercises for in vitro "surprise" analysis when no information is available on the nuclides involved, which can be the case in an emergency situation.

Medical management of a cutaneous contamination.

The authors propose a process to improve the medical management of a cutaneous contamination in two ways: firstly by analysis of practices and products of decontamination used; secondly, by developing computer tools for the occupational physicians. This software will allow them to have a rapid dosimetric assessment in the event of a skin contamination by radioactive particles and will help them in their diagnostic and therapeutic decisions. A standardized data sheet was created allowing the exhaustive collection of adequate information in order to evaluate the skin dose. The selection of appropriate monitoring equipment with a 1 cm2 detector, depending on the place and on the surface of the contaminated area, will allow the evaluation and the quantification of the surface activities. A tool has been made as a software package, named Cutadose®, allowing the assessment of the skin dose in situ as well as the efficacy of the prescribed therapy.

The CONRAD approach to biokinetic modeling of DTPA decorporation therapy.

Diethylene Triamine Pentaacetic Acid (DTPA) is used for decorporation of plutonium because it is known to be able to enhance its urinary excretion for several days after treatment by forming stable Pu-DTPA complexes. The decorporation prevents accumulation in organs and results in a dosimetric benefit, which is difficult to quantify from bioassay data using existing models. The development of a biokinetic model describing the mechanisms of actinide decorporation by administration of DTPA was initiated as a task in the European COordinated Network on RAdiation Dosimetry (CONRAD). The systemic biokinetic model from Leggett et al. and the biokinetic model for DTPA compounds of International Commission on Radiological Protection Publication 53 were the starting points. A new model for biokinetics of administered DTPA based on physiological interpretation of 14C-labeled DTPA studies from literature was proposed by the group. Plutonium and DTPA biokinetics were modeled separately. The systems were connected by means of a second order kinetics process describing the chelation process of plutonium atoms and DTPA molecules to Pu-DTPA complexes. It was assumed that chelation only occurs in the blood and in systemic compartment ST0 (representing rapid turnover soft tissues), and that Pu-DTPA complexes and administered forms of DTPA share the same biokinetic behavior. First applications of the CONRAD approach showed that the enhancement of plutonium urinary excretion after administration of DTPA was strongly influenced by the chelation rate constant. Setting it to a high value resulted in a good fit to the observed data. However, the model was not yet satisfactory since the effects of repeated DTPA administration in a short time period cannot be predicted in a realistic way. In order to introduce more physiological knowledge into the model several questions still have to be answered. Further detailed studies of human contamination cases and experimental data will be needed in order to address these issues. The work is now continued within the European Radiation Dosimetry Group, EURADOS.

Comparative assessing for radiological, chemical, and physical exposures at the French uranium conversion plant: Is uranium the only stressor?

This study presents the pattern of exposure to uranium and other occupational pollutants known to be potentially carcinogenic, mutagenic or toxic and used at the main uranium conversion plant in France. For different uranium compounds specified according to their solubility and purity, and 16 other categories of pollutants: chemicals, fibres, vapours, dust, and heat a time- and plant-specific job exposure matrix (JEM) was created covering the period 1960-2006. For 73 jobs and for each pollutant the amount and frequency of exposure were assessed on a four-level scale by different time periods. The JEM shows 73% sensitivity and 83% specificity. Although exposure assessment was semi-quantitative, the JEM allows computing of individual cumulative exposure score for each pollutant across time. Despite the predominant natural uranium compounds exposure, the amount of exposure to other pollutants such as TCE and other chlorinated products, asbestos, and fibres, is important at the plant. Numerous correlations detected between uranium compounds exposure and exposure to chemicals warrants improving biological monitoring of exposed workers and accounting for associated exposures in epidemiological studies. Results of this study will be used for further investigation of association between exposure and mortality among uranium conversion workers cohort.

Comparison of analytical and algebraic 2D tomographic reconstruction approaches for irregularly sampled microCT data.

APD-based detectors with individual channel readout were developed for multi-crystal applications and have been implemented for the detection of annihilation radiation in the LabPET micro-scanner. The use of these APD-based detectors in X-ray imaging is currently being assessed with a microCT demonstrator in order to later combine PET and CT in one apparatus. This paper is focused on the tomographic reconstruction of the X-ray transmission data acquired with this demonstrator. Two aspects of the acquisition geometry need to be carefully considered: the radius of the detector arc and the irregular sampling of the detector bins. A specific shift-variant filtered backprojection formula derived to account for the detector curvature is applied to equiangularly resampled projection data while the simultaneous algebraic reconstruction technique is applied to both resampled and original projections. Images of physical phantoms reconstructed from measured projections using the different methods are presented and compared.