Methods of improving brain dose estimates for internally deposited radionuclides.

The US National Council on Radiation Protection and Measurements (NCRP) convened Scientific Committee 6-12 (SC 6-12) to examine methods for improving dose estimates for brain tissue for internally deposited radionuclides, with emphasis on alpha emitters. This Memorandum summarises the main findings of SC 6-12 described in the recently published NCRP Commentary No. 31, 'Development of Kinetic and Anatomical Models for Brain Dosimetry for Internally Deposited Radionuclides'. The Commentary examines the extent to which dose estimates for the brain could be improved through increased realism in the biokinetic and dosimetric models currently used in radiation protection and epidemiology. A limitation of most of the current element-specific systemic biokinetic models is the absence of brain as an explicitly identified source region with its unique rate(s) of exchange of the element with blood. The brain is usually included in a large source region calledOtherthat contains all tissues not considered major repositories for the element. In effect, all tissues inOtherare assigned a common set of exchange rates with blood. A limitation of current dosimetric models for internal emitters is that activity in the brain is treated as a well-mixed pool, although more sophisticated models allowing consideration of different activity concentrations in different regions of the brain have been proposed. Case studies for 18 internal emitters indicate that brain dose estimates using current dosimetric models may change substantially (by a factor of 5 or more), or may change only modestly, by addition of a sub-model of the brain in the biokinetic model, with transfer rates based on results of published biokinetic studies and autopsy data for the element of interest. As a starting place for improving brain dose estimates, development of biokinetic models with explicit sub-models of the brain (when sufficient biokinetic data are available) is underway for radionuclides frequently encountered in radiation epidemiology. A longer-term goal is development of coordinated biokinetic and dosimetric models that address the distribution of major radioelements among radiosensitive brain tissues.

Four-decade follow-up of a plutonium-contaminated puncture wound treated with Ca-DTPA.

Contaminated wounds are a common route of internal deposition of radionuclides for nuclear and radiation workers. They may result in significant doses to radiosensitive organs and tissues in an exposed individual's body. The United States Transuranium and Uranium Registries' whole-body donor (Case 0303) accidentally punctured his finger on equipment contaminated with plutonium nitrate. The wound was surgically excised and medically treated with intravenous injections of Ca-DTPA. A total of 16 g Ca-DTPA was administered in 18 treatments during the 2 months following the accident. Ninety-three urine samples were collected and analysed over 14 years following the accident. An estimated239Pu activity of 73.7 Bq was excreted during Ca-DTPA treatment. Post-mortem radiochemical analysis of autopsy tissues indicated that 40 years post-accident 21.6 ± 0.2 Bq of239Pu was retained in the skeleton, 12.2 ± 0.3 Bq in the liver, and 3.7 ± 0.1 Bq in other soft tissues; 1.35 ± 0.02 Bq of239Pu was measured in tissue samples from the wound site. To estimate the plutonium intake, late urine measurements, which were unaffected by chelation, and post-mortem radiochemical analysis results were evaluated using the IMBA Professional Plus software. The application of the National Council on Radiation Protection and Measurements wound model with an assumption of intake material as a predominantly strongly retained soluble plutonium compound with a small insoluble fraction adequately described the data (p= 0.46). The effective intake was estimated to be 50.2 Bq of plutonium nitrate and 1.5 Bq of the fragment. The prompt medical intervention with contaminated tissue excision and subsequent Ca-DTPA decorporation therapy reduced239Pu activity available for uptake and long-term retention in this individual's systemic organs by a factor of 38.

Modelling of long-term retention of high-fired plutonium oxide in the human respiratory tract: importance of scar-tissue compartments.

The U.S. Transuranium and Uranium Registries whole-body tissue donor Case 0407 had an acute intake of 'high-fired' plutonium oxide resulting from a glove-box fire in a fabrication plant at a nuclear defence facility. The respiratory tract of this individual was dissected into five regions (larynx, bronchi, bronchioles, alveolar-interstitial, and thoracic lymph nodes) and analysed for plutonium content. The activities in certain compartments of the respiratory tract were found to be higher than expected from the default models described in publications of the International Commission on Radiological Protection. Because of the extremely slow rate of dissolution of the material inhaled, the presence of bound fraction is incapable of explaining the higher-than-expected retention. A plausible hypothesis-encapsulation of plutonium in scar tissues-is supported by the review of literature. Therefore, scar-tissue compartments corresponding to the larynx, bronchi, bronchioles and alveolar-interstitial regions were added to the existing human respiratory tract model structure. The transfer rates between these compartments were determined using Markov Chain Monte Carlo analysis of data on urinary excretion, lung counts and post-mortem measurements of the liver, skeleton and regional retention in the respiratory tract. Modelling of the data showed that approximately 30% of plutonium activity in the lung was sequestered in scar tissues. The dose consequence of such sequestration is qualitatively compared against that of chemical binding.

Validation of a system of models for plutonium decorporation therapy.

A recently proposed system of models for plutonium decorporation (SPD) was developed using data from an individual occupationally exposed to plutonium via a wound [from United States Transuranium and Uranium Registries (USTUR) Case 0212]. The present study evaluated the SPD using chelation treatment data, urine measurements, and post-mortem plutonium activities in the skeleton and liver from USTUR Case 0269. This individual was occupationally exposed to moderately soluble plutonium via inhalation and extensively treated with chelating agents. The SPD was linked to the International Commission on Radiological Protection (ICRP) Publication 66 Human Respiratory Tract Model (HRTM) and the ICRP Publication 30 Gastrointestinal Tract model to evaluate the goodness-of-fit to the urinary excretion data and the predictions of post-mortem plutonium retention in the skeleton and liver. The goodness-of-fit was also evaluated when the SPD was linked to the ICRP Publication 130 HRTM and the ICRP Publication 100 Human Alimentary Tract Model. The present study showed that the proposed SPD was useful for fitting the entire, chelation-affected and non-affected, urine bioassay data, and for predicting the post-mortem plutonium retention in the skeleton and liver at time of death, 38.5 years after the accident. The results of this work are consistent with the conclusion that Ca-EDTA is less effective than Ca-DTPA for enhancing urinary excretion of plutonium.

US Transuranium and Uranium Registries case study on accidental exposure to uranium hexafluoride.

The United States Transuranium and Uranium Registries' (USTUR) whole-body donor (Case 1031) was exposed to an acute inhalation of uranium hexafluoride (UF6) produced from an explosion at a uranium processing plant 65 years prior to his death. The USTUR measurements of tissue samples collected at the autopsy indicated long-term retention of inhaled slightly enriched uranium material (0.85% (235)U) in the deep lungs and thoracic lymph nodes. In the present study, the authors combined the tissue measurement results with historical bioassay data, and analysed them with International Commission on Radiological Protection (ICRP) respiratory tract models and the ICRP Publication 69 systemic model for uranium using maximum likelihood and Bayesian statistical methods. The purpose of the analysis was to estimate intakes and model parameter values that best describe the data, and evaluate their effect on dose assessment. The maximum likelihood analysis, which used the ICRP Publication 66 human respiratory tract model, resulted in a point estimate of 79 mg of uranium for the occupational intake composed of 86% soluble, type F material and 14% insoluble, type S material. For the Bayesian approach, the authors applied the Markov Chain Monte Carlo method, but this time used the revised human respiratory tract model, which is currently being used by ICRP to calculate new dose coefficients for workers. The Bayesian analysis estimated that the mean uranium intake was 160 mg, and calculated the case-specific lung dissolution parameters with their associated uncertainties. The parameters were consistent with the inhaled uranium material being predominantly soluble with a small but significant insoluble component. The 95% posterior range of the rapid dissolution fraction (the fraction of deposited material that is absorbed to blood rapidly) was 0.12 to 0.91 with a median of 0.37. The remaining fraction was absorbed slowly, with a 95% range of 0.000 22 d(-1) to 0.000 36 d(-1) and a median of 0.000 31 d(-1). The effective dose per unit intake calculated using the dissolution parameters derived from the maximum likelihood and the Bayesian analyses was higher than the current ICRP dose coefficient for type F uranium by a factor of 2 or 7, respectively; the higher value of the latter was due to use of the revised respiratory tract model. The dissolution parameter values obtained here may be more appropriate to use for radiation protection purposes when individuals are exposed to a UF6 mixture that contains an insoluble uranium component.

Latent bone modelling for estimation of plutonium concentration in skeleton of former nuclear workers.

The skeleton is a major plutonium retention site in the human body. Estimation of the total plutonium activity in the skeleton is a challenging problem. For most tissue donors at the United States Transuranium and Uranium Registries, a limited number of bone samples is available. The skeleton activity is calculated using plutonium activity concentration (Cskel) and skeleton weight. In this study, latent bone modelling was used to estimate Cskel from the limited number of analysed bone samples. Data from 13 non-osteoporotic whole-body donors were used to develop latent bone model (LBM) to estimate Cskel for seven cases with four to eight analysed bone samples. LBM predictions were compared to Cskel estimated using an arithmetic mean in terms of accuracy and precision. For the studied cases, LBM offered a significant reduction of uncertainty of Cskel estimate.

Modified human respiratory tract model to describe the retention of plutonium in scar tissues.

The Human Respiratory Tract Model described in Publication 130 of the International Commission on Radiological Protection provides some mechanisms to account for retention of material that can be subject to little to no mechanical transport or absorption into the blood. One of these mechanisms is 'binding', which refers to a process by which a fraction ('bound fraction') of the dissolved material chemically binds to the tissue of the airway wall. The value of the bound fraction can have a significant impact on the radiation doses imparted to different parts of the respiratory tract. To properly evaluate-and quantify-bound fraction for an element, one would need information on long-term retention of the element in individual compartments of the respiratory tract. Such data on regional retention of plutonium in the respiratory tract of four workers-who had inhaled materials with solubility ranging from soluble nitrate to very insoluble high-fired oxides-were obtained at the United States Transuranium and Uranium Registries. An assumption of bound fraction alone was found to be inconsistent with this dataset and also with a review of the literature. Several studies show evidence of retention of a large amount of Pu activity in the scar tissues of humans and experimental animals, and accordingly, a model structure with scar-tissue compartments was proposed. The transfer rates to these compartments were determined using Markov Chain Monte Carlo analysis of the bioassay and post-mortem data, considering the uncertainties associated with deposition, dissolution and particle clearance parameters. The models predicted that a significant amount-between 20 and 100% for the cases analyzed-of plutonium retained in the respiratory tract was sequestered in the scar tissues. Unlike chemically-bound Pu that irradiates sensitive epithelial cells, Pu in scar tissues may not be dosimetrically significant because the scar tissues absorb most, if not all, of the energy from alpha emissions.

Potential improvements in brain dose estimates for internal emitters.

BACKGROUND: Element-specific biokinetic models are used to reconstruct doses to systemic tissues from internal emitters. Typically, a systemic model for a radionuclide explicitly depicts only its dominant repositories. Remaining tissues and fluids are aggregated into a pool called Other tissue in which the radionuclide is assumed to be uniformly distributed. In the systemic biokinetic models used in radiation protection, the brain usually is addressed as an implicit mass fraction of Other tissue rather than an explicitly depicted repository. Due to increasing interest in radiation effects on the brain, efforts are underway to improve brain dosimetry for internal radiation sources. METHODS: We assessed potential improvements in brain dosimetry for internal emitters by explicitly modeling brain kinetics rather than treating the brain as a mass fraction of Other tissue. We selected 10 elements for which brain kinetics can be modeled using published biokinetic data. Injection dose coefficients were calculated for a relatively long-lived radioisotope of each element using each of two versions of the ICRP's latest systemic biokinetic model for the element, the original version and a modified version differing only in the treatment of brain. If the ICRP model contained an explicit brain pool, the modified version depicted brain instead as a mass fraction of Other tissue. If the ICRP model included brain in Other tissue, the modified version included an explicit brain pool with kinetics based on best available brain-specific data. RESULTS: The result for a given radionuclide is expressed as a ratio A:B, where A and B are the dose coefficients based on the versions of the model with and without an explicit brain pool, respectively. The following ratios A:B were obtained for the 10 radionuclides addressed here: 241Am, 0.13; 207Bi, 0.57; 234U, 0.81; 239Pu, 0.96; 203Hg (vapor), 1.4; 134Cs, 1.5; 54Mn, 1.7; 210Po, 1.7; 226Ra, 1.9; 210Pb, 3.3. These ratios indicate that a dose estimate for brain based on a biokinetic model with brain implicitly contained in Other tissue may substantially underestimate or substantially overestimate a dose estimate that reflects best available brain-specific biokinetic data. Of course, the reliability of the latter estimate depends on the quality of the underlying biokinetic data. CONCLUSIONS: Where feasible, the brain should be depicted explicitly in biokinetic models used in epidemiological studies addressing adverse effects of ionizing radiation.

A million persons, a million dreams: a vision for a national center of radiation epidemiology and biology.

BACKGROUND: Epidemiologic studies of radiation-exposed populations form the basis for human safety standards. They also help shape public health policy and evidence-based health practices by identifying and quantifying health risks of exposure in defined populations. For more than a century, epidemiologists have studied the consequences of radiation exposures, yet the health effects of low levels delivered at a low-dose rate remain equivocal. MATERIALS AND METHODS: The Million Person Study (MPS) of U.S. Radiation Workers and Veterans was designed to examine health effects following chronic exposures in contrast with brief exposures as experienced by the Japanese atomic bomb survivors. Radiation associations for rare cancers, intakes of radionuclides, and differences between men and women are being evaluated, as well as noncancers such as cardiovascular disease and conditions such as dementia and cognitive function. The first international symposium, held November 6, 2020, provided a broad overview of the MPS. Representatives from four U.S. government agencies addressed the importance of this research for their respective missions: U.S. Department of Energy (DOE), the Centers for Disease Control and Prevention (CDC), the U.S. Department of Defense (DOD), and the National Aeronautics and Space Administration (NASA). The major components of the MPS were discussed and recent findings summarized. The importance of radiation dosimetry, an essential feature of each MPS investigation, was emphasized. RESULTS: The seven components of the MPS are DOE workers, nuclear weapons test participants, nuclear power plant workers, industrial radiographers, medical radiation workers, nuclear submariners, other U.S. Navy personnel, and radium dial painters. The MPS cohorts include tens of thousands of workers with elevated intakes of alpha particle emitters for which organ-specific doses are determined. Findings to date for chronic radiation exposure suggest that leukemia risk is lower than after acute exposure; lung cancer risk is much lower and there is little difference in risks between men and women; an increase in ischemic heart disease is yet to be seen; esophageal cancer is frequently elevated but not myelodysplastic syndrome; and Parkinson's disease may be associated with radiation exposure. CONCLUSIONS: The MPS has provided provocative insights into the possible range of health effects following low-level chronic radiation exposure. When the 34 MPS cohorts are completed and combined, a powerful evaluation of radiation-effects will be possible. This final article in the MPS special issue summarizes the findings to date and the possibilities for the future. A National Center for Radiation Epidemiology and Biology is envisioned.

Inhalation of Soluble Plutonium: 53-year Follow-up of Manhattan Project Worker.

ABSTRACT: This whole-body tissue donor to the United States Transuranium and Uranium Registries was occupationally exposed to plutonium nitrate-dioxide mixture via chronic inhalation. This individual was involved in the Manhattan Project operations and later participated in medical follow-up studies. Soft tissues and bones collected at autopsy were analyzed for 238Pu, 239+240Pu, and 241Am. Fifty-three years post-intake, 700±2 Bq of 239+240Pu were still retained in the skeleton, 661±11 Bq in the liver, and 282±3 Bq in the respiratory tract. Bioassay measurements and organ activities at the time of death were used to estimate the intake and radiation doses using the TAURUS internal dosimetry software. For this individual, an ICRP Publication 130 Human Respiratory Tract Model with case-specific particle size of 0.3 µm, ICRP Publication 100 Human Alimentary Tract Model, and ICRP Publication 141 Plutonium Systemic Model adequately described long-term plutonium retention and excretion. The total cumulative 239+240Pu intake of 31,716 Bq was estimated, of which 24,853 Bq (78.4%) were contributed by inhalation of plutonium nitrate and 6,863 Bq (21.6%) of plutonium dioxide. The committed equivalent doses to the red bone marrow, bone surface, liver, lungs, and brain were 0.71 Sv, 6.5 Sv, 8.3 Sv, 3.8 Sv, and 0.068 Sv, respectively. The committed effective dose was 1.22 Sv.

Plutonium in Manhattan Project workers: Using autopsy data to evaluate organ content and dose estimates based on urine bioassay with implications for radiation epidemiology.

PURPOSE: Radiation dose estimates in epidemiology typically rely on intake predictions based on urine bioassay measurements. The purpose of this article is to compare the conventional dosimetric estimates for radiation epidemiology with the estimates based on additional post-mortem tissue radiochemical analysis results. METHODS: The comparison was performed on a unique group of 11 former Manhattan Project nuclear workers, who worked with plutonium in the 1940s, and voluntarily donated their bodies to the United States Transuranium and Uranium Registries. RESULTS: Post-mortem organ activities were predicted using different sets of urine data and compared to measured activities. Use of urinalysis data collected during the exposure periods overestimated the systemic (liver+skeleton) deposition of 239Pu by 155±134%, while the average bias from using post-exposure urinalyses was -4±50%. Committed effective doses estimated using early urine data differed from the best estimate by, on average, 196±193%; inclusion of follow-up urine measurements in analyses decreased the mean bias to 0.6±36.3%. Cumulative absorbed doses for the liver, red marrow, bone surface, and brain were calculated for the actual commitment period. CONCLUSION: On average, post-exposure urine bioassay results were in good agreement with post-mortem tissue analyses and were more reliable than results of urine bioassays collected during the exposure.

Long-term Retention of Plutonium in the Respiratory Tracts of Two Acutely-exposed Workers: Estimation of Bound Fraction.

ABSTRACT: Inhalation of plutonium is a significant contributor of occupational doses in plutonium production, nuclear fuel reprocessing, and cleanup operations. Accurate assessment of the residence time of plutonium in the lungs is important to properly characterize dose and, consequently, the risk from inhalation of plutonium aerosols. This paper discusses the long-term retention of plutonium in different parts of the respiratory tract of two workers who donated their bodies to the US Transuranium and Uranium Registries. The post-mortem tissue radiochemical analysis results, along with the urine bioassay data, were interpreted using Markov Chain Monte Carlo and the latest biokinetic models presented in the Occupational Intakes of Radionuclides series of ICRP publications. The materials inhaled by both workers were found to have solubility between that of plutonium nitrates and oxides. The long-term solubility was also confirmed by comparison of the activity concentration in the lungs and the thoracic lymph nodes. The data from the two individuals can be explained by assuming a bound fraction (fraction of plutonium deposited in the respiratory tract that becomes bound to lung tissue after dissolution) of 1% and 4%, respectively, without having to significantly alter the particle clearance parameters. Effects of different assumptions about the bound fraction on radiation doses to different target regions was also investigated. For inhalation of soluble materials, an assumption of fb of 1%, compared to the ICRP default of 0.2%, increases the dose to the most sensitive target region of the respiratory tract by 258% and that to the total lung by 116%. Some possible alternate methods of explaining higher-than-expected long-term retention of plutonium in the upper respiratory tract of these individuals-such as physical sequestration of material into the scar tissues and possible uptake by lungs-are also briefly discussed.

MODELING THE LONG-TERM RETENTION OF PLUTONIUM IN THE HUMAN RESPIRATORY TRACT USING SCAR-TISSUE COMPARTMENTS.

The respiratory tract tissues of four former nuclear workers with plutonium intakes were radiochemically analyzed post mortem by the United States Transuranium and Uranium Registries. Plutonium activities in the upper respiratory tract of these individuals were found to be higher than those predicted using the most recent biokinetic models described in publications of the International Commission on Radiological Protection. Modification of the model parameters, including the bound fraction, was not able to explain the data in one of the four individuals who had inhaled insoluble form of plutonium. Literature review points to the presence of-and a significant retention of-plutonium in the scar tissues of the lungs. Accordingly, an alternate model with scar-tissue compartments corresponding to larynx, bronchi, bronchioles, alveolar-interstitium and thoracic lymph nodes was proposed. The rates of transfer to the scar tissue compartments were determined using Markov Chain Monte Carlo analysis of data on urinary excretion, lung counts and post-mortem measurements of liver, skeleton and individual respiratory tract compartments, as available. The posterior models predicted that 20-100%-depending on the solubility of the material inhaled-of the activities retained in the respiratory tract were sequestered in the scar tissues.

Modeling the Skeleton Weight of an Adult Caucasian Man.

The reference value for the skeleton weight of an adult male (10.5 kg) recommended by the International Commission on Radiological Protection in Publication 70 is based on weights of dissected skeletons from 44 individuals, including two US Transuranium and Uranium Registries whole-body donors. The International Commission on Radiological Protection analysis of anatomical data from 31 individuals with known values of body height demonstrated significant correlation between skeleton weight and body height. The corresponding regression equation, Wskel (kg) = -10.7 + 0.119 × H (cm), published in International Commission on Radiological Protection Publication 70 is typically used to estimate the skeleton weight from body height. Currently, the US Transuranium and Uranium Registries holds data on individual bone weights from a total of 40 male whole-body donors, which has provided a unique opportunity to update the International Commission on Radiological Protection skeleton weight vs. body height equation. The original International Commission on Radiological Protection Publication 70 and the new US Transuranium and Uranium Registries data were combined in a set of 69 data points representing a group of 33- to 95-y-old individuals with body heights and skeleton weights ranging from 155 to 188 cm and 6.5 to 13.4 kg, respectively. Data were fitted with a linear least-squares regression. A significant correlation between the two parameters was observed (r = 0.28), and an updated skeleton weight vs. body height equation was derived: Wskel (kg) = -6.5 + 0.093 × H (cm). In addition, a correlation of skeleton weight with multiple variables including body height, body weight, and age was evaluated using multiple regression analysis, and a corresponding fit equation was derived: Wskel (kg) = -0.25 + 0.046 × H (cm) + 0.036 × Wbody (kg) - 0.012 × A (y). These equations will be used to estimate skeleton weights and, ultimately, total skeletal actinide activities for biokinetic modeling of US Transuranium and Uranium Registries partial-body donation cases.

Evaluating Plutonium Intake and Radiation Dose Following Extensive Chelation Treatment.

A voluntary partial-body donor (US Transuranium and Uranium Registries case 0785) was accidentally exposed to Pu via inhalation and wounds. This individual underwent medical treatment including wound excision and extensive chelation treatment with calcium ethylenediaminetetraacetic acid and calcium diethylenetriaminepentaacetic acid. Approximately 2.2 kBq of Pu was measured in the wound site 44 y after the accident. Major soft tissues and selected bones were collected at autopsy and radiochemically analyzed for Pu, Pu, and Am. Postmortem systemic retention of Pu, Pu, and Am was estimated to be 32.0 ± 1.4 Bq, 2,172 ± 70 Bq, and 394 ± 15 Bq, respectively. Approximately 3% of Pu whole-body activity was still retained in the lungs 51 y after the accident indicating exposure to insoluble plutonium material. To estimate the intake and calculate radiation dose, urine measurements not affected by chelation treatment, in vivo chest counts, and postmortem radiochemical analysis data were simultaneously fitted using Integrated Modules for Bioassay Analysis Professional Plus software. The currently recommended International Commission on Radiological Protection Publication 130 human respiratory tract model and National Council on Radiation Protection and Measurements Report 156 wound model were used with default parameters. The intake, adjusted for Pu removed by chelation treatment, was estimated at approximately 79.5 kBq with 68% resulting from inhalation and 32% from the wound. Inhaled plutonium was predominantly insoluble type S material (74%) with insoluble plutonium fragments deposited in the wound. Only 1.3% reduction in radiation dose was achieved by chelation treatment. The committed effective dose was calculated to be 1.49 Sv. Using urine data available for this case, the effect of chelation therapy was evaluated. Urinary excretion enhancement factors were calculated as 83 ± 52 and 38 ± 17 for initial and delayed calcium ethylenediaminetetraacetic acid treatments, respectively, and as 18 ± 5 for delayed calcium diethylenetriaminepentaacetic acid. The enhancement factor decreases proportionally to an inverse cubic root of time after intake. For delayed calcium ethylenediaminetetraacetic acid treatment, with five consecutive daily administrations, the enhancement factor increased from day 1 to 4, followed by approximately a 50% drop on day 5. The half-time of plutonium ethylenediaminetetraacetic acid complex removal in urine was evaluated to be 1.4 d.

The US Transuranium and Uranium Registries (USTUR): A Five-Decade Follow-Up Of Plutonium and Uranium Workers.

Dedication: The research of the US Transuranium and Uranium Registries relies heavily upon postmortem autopsy findings and radiochemical analysis of tissues. The enormous debt owed to those now-deceased registrants who unselfishly voluntarily participated in the US Transuranium and Uranium Registries program through postmortem donation of their tissues and to those still-living registrants who have volunteered to be future postmortem tissue donors is hereby acknowledged with gratitude. The scientific findings derived from postmortem analysis of these tissues have been instrumental in advancing our understanding of the actinide elements in humans and have led to refinement, validation, and confidence in safety standards for those who work with these elements as well as for the general public. To these generous and anonymous persons who made this ultimate contribution, this paper is dedicated with great thanks and admiration.

The Importance and Quantification of Plutonium Binding in Human Lungs.

Epidemiological studies have shown that the main risk arising from exposure to plutonium aerosols is lung cancer, with other detrimental effects in the bone and liver. A realistic assessment of these risks, in turn, depends on the accuracy of the dosimetric models used to calculate doses in such studies. A state-of-the-art biokinetic model for plutonium, based on the current International Commission on Radiological Protection biokinetic model, has been developed for this purpose in an epidemiological study involving the plutonium exposure of Mayak workers in Ozersk, Russia. One important consequence of this model is that the lung dose is extremely sensitive to the fraction (fb) of plutonium, which becomes bound to lung tissue after it dissolves. It has been shown that if just 1% of the material becomes bound in the bronchial region, this will double the lung dose. Furthermore, fb is very difficult to quantify from experimental measurements. This paper summarizes the work carried out thus far to quantify fb. Bayesian techniques have been used to analyze data from different sources, including both humans and dogs, and the results suggest a small, but nonzero, fraction of < 1%. A Bayesian analysis of 20 Mayak workers exposed to plutonium nitrate suggests an fb between 0 and 0.3%. Based on this work, the International Commission on Radiological Protection is currently considering the adoption of a value of 0.2% for the default bound fraction for all actinides in its forthcoming recommendations on internal dosimetry. In an attempt to corroborate these findings, further experimental work has been carried out by the US Transuranium and Uranium Registries. This work has involved direct measurements of plutonium in the respiratory tract tissues of workers who have been exposed to soluble plutonium nitrate. Without binding, one would not expect to see any activity remaining in the lungs at long times after exposure since it would have been cleared by the natural process of mucociliary clearance. Further supportive study of workers exposed to plutonium oxide is planned. This paper ascertains the extent to which these results corroborate previous inferences concerning the bound fraction.

Mapping 241Am Spatial Distribution Within Anatomical Bone Structures Using Digital Autoradiography.

Digital autoradiography with the ionizing radiation quantum imaging detector is used at the US Transuranium and Uranium Registries for visualizing the microdistribution of alpha particles from Am and quantifying the activity. The radionuclide spatial distribution was investigated within cortical and trabecular regions of bone samples from US Transuranium and Uranium Registries case 0846. Multiple specimens from the humerus proximal end, humerus proximal shaft, and clavicle acromial end were embedded in plastic, and 100-µm-thick sections were taken and imaged using the ionizing radiation quantum imaging detector. The detector images were superimposed on the anatomical structure images to visualize Am distribution in cortical bone, trabecular bone, and trabecular spongiosa. Activity concentration ratios were used to characterize Am distribution within different bone regions. The trabecular-to-cortical bone and trabecular-spongiosa-to-cortical bone activity concentration ratios were quantified in both humerus and clavicle. The ionizing radiation quantum imaging detector results were in agreement with those obtained from radiochemical analysis of the remaining bone specimens. The results were compared with International Commission on Radiological Protection default biokinetic model predictions. Digital autoradiography was proven to be an effective method for microscale heterogeneous distribution studies where traditional counting methods are impractical.

Ustur Case 0846: Modeling Americium Biokinetics after Intensive Decorporation Therapy.

Decorporation therapy with salts of diethylenetriamine-pentaacetic acid binds actinides, thereby limiting uptake to organs and enhancing the rate at which actinides are excreted in urine. International Commission on Radiological Protection reference biokinetic models cannot be used to fit this enhanced exertion simultaneously with the baseline actinide excretion rate that is observed prior to the start of therapy and/or after the effects of therapy have ceased. In this study, the Coordinated Network on Radiation Dosimetry approach, which was initially developed for modeling decorporation of plutonium, was applied to model decorporation of americium using data from a former radiation worker who agreed to donate his body to the US Transuranium and Uranium Registries for research. This individual was exposed to airborne Am, resulting in a total-body activity of 66.6 kBq. He was treated with calcium-diethylenetriamine-pentaacetic acid for 7 y. The time and duration of intakes are unknown as no incident reports are available. Modeling of different assumptions showed that an acute intake of 5-µm activity median aerodynamic diameter type M aerosols provides the most reasonable description of the available pretherapeutic data; however, the observed Am activity in the lungs at the time of death was higher than the one predicted for type M material. The Coordinated Network on Radiation Dosimetry approach for decorporation modeling was used to model the in vivo chelation process directly. It was found that the Coordinated Network on Radiation Dosimetry approach, which only considered chelation in blood and extracellular fluids, underestimated the urinary excretion of Am during diethylenetriamine-pentaacetic acid treatment; therefore, the approach was extended to include chelation in the liver. Both urinary excretion and whole-body retention could be described when it was assumed that 25% of chelation occurred in the liver, 75% occurred in the blood and ST0 compartment, and the chelation rate constant was 1 × 10 pmol d. It was observed that enhancement of urinary excretion of Am after injection of diethylenetriamine-pentaacetic acid exponentially decreased to the baseline level with an average half-time of 2.2 ± 0.7 d.

Estimation of Total Skeletal Content of Plutonium and 241Am From Analysis of a Single Bone.

The skeleton is one of the major retention sites for internally deposited actinides. Thus, an accurate estimation of the total skeleton content of these elements is important for biokinetic modeling and internal radiation dose assessment. Data from 18 whole-body donations to the US Transuranium and Uranium Registries with known plutonium intakes were used to develop a simple and reliable method for estimation of plutonium and Am activity in the total skeleton from single-bone analysis. A coefficient of deposition Kdep, defined as the ratio of actinide content in the patella to that in the skeleton, was calculated for Pu, Pu, and Am. No statistical difference was found in Kdep values among these radionuclides. Variability in Kdep values was investigated with relation to skeleton pathology (osteoporosis). The average Kdep of 0.0051 ± 0.0009 for the osteoporotic group was statistically different from Kdep of 0.0032 ± 0.0010 for nonosteoporotic individuals. The use of Kdep allows for rapid estimation of the total skeletal content of plutonium and Am with up to 35% uncertainty. To improve accuracy and precision of total skeleton activity estimates, regression analysis with power function was applied to the data. Strong correlation (r > 0.9) was found between Pu, Pu, and Am activities measured in the patella bone and total skeleton activity. The results of this study are specifically important for the optimization of bone sample collection for US Transuranium and Uranium Registries partial-body donations.