The 61st Annual Meeting of the Health Physics Society

17-21 July 2016, Spokane, WA

Single Session



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TPM-A - Technical Session II: USTUR Collaborative Research

100 C   14:30 - 17:15

Chair(s): Isaf Al-Nabulsi, Ray Guilmette
 
TPM-A.1   14:30  Red Marrow Dosimetry for Former Radium Workers RE Toohey*, M.H. Chew & Assoc. ; RE Goans, MJW Corp.; CJ Iddins, ORISE; N Dainiak, ORISE; SL McComish, USTUR; SY Tolmachev, USTUR

Abstract: A collaboration between the Radiation Emergency Assistance Center and Training Site (REAC/TS) at the Oak Ridge Institute for Science and Education (ORISE) in Oak Ridge, TN and the United States Transuranium and Uranium Registries (USTUR) at Washington State University in Richland, WA has resulted in the discovery of a possible long-term biodosimeter that could be useful for population screening and/or epidemiological studies. The pseudo-Pelger-Huet (pseudo-P-H) anomaly consists of characteristic bi-lobed nuclei in neutrophils that can be easily assessed by light microscopy of a peripheral blood (PB) smear. Since PB cell culture is not required (as with dicentric chromosome analysis), a marked reduction in time to obtain results is achieved. A set of 166 PB smears from former workers in the luminizing industry was provided by the USTUR from the National Human Radiobiology Tissue Repository and examined at REAC/TS; the anomaly was characterized as the percentage of pseudo-P-H cells among neutrophils. The radium intakes of most of the subjects are given in R. E. Rowland’s publication, Radium in Humans: A Review of U.S. Studies (1994). The published intakes, based on whole-body counts, had to be modified to accommodate changes in the ICRP biokinetic model for radium since they were originally calculated. Red marrow doses were computed from the adjusted intakes of 226Ra and 228Ra by using the ingestion dose coefficients given in ICRP Publication 67. However, because many of the workers started in their teens, doses were adjusted for age at intake; the dose coefficient for a 15-year-old was used for intakes occurring before age 25, and the adult dose coefficient was used for intakes at age 25 and above. Starting dates of exposure ranged from 1914 to 1950, and ages at first exposure ranged from 13 to 40 years. Exposure durations ranged from 1 to 1800 weeks and the vast majority of these PB samples were drawn between 1973 and 1975 at the time of the whole-body counts. Calculated red marrow doses ranged from zero to 13.6 Gy-eq, computed with a radiation weighting factor of two for alpha particles producing tissue reaction effects. A companion paper by R. E. Goans et al. presents the dose-response data for the pseudo-P-H anomaly in these cases. *Acknowledgements: this work was supported by the U.S. Department of Energy under contract number DE-AC05-06OR23100 with Oak Ridge Associated Universities and award number DE-HS0000073 to Washington State University. The U.S. government retains a non-exclusive copyright on this work to use for government purposes.

TPM-A.2   14:45  The Pseudo Pelger-Huet Cell as a Retrospective Dosimeter: Analysis of a Radium Dial Painter Cohort RE Goans*, MJW Corporation ; RE Toohey, M.H. Chew and Associates; CJ Iddins, ORISE; N Daniak, ORISE; SL McComish, USTUR; SY Tolmachev, USTUR

Abstract: Recently the pseudo-Pelger Huët anomaly (PHA) in peripheral blood neutrophils was described as a new radiation-induced, stable biomarker (Goans et al. Health Phys 108(3), 2015). In this study, we have examined PHA in peripheral blood slides from a cohort of 166 former radium dial painters, 35 of whom had zero marrow dose. The slides were made available in collaboration with the US Transuranium and Uranium Registry (USTUR). Members of the radium dial painter cohort had ingestion of 226Ra and 228Ra at an early age (average age 20.6 ± 5.4 y; range 13-40 y) during the years 1914-1955. Exposure duration ranged from 1-1820 weeks with marrow dose 3-13,500 mGy-Eq. Red marrow alpha dosimetry for this study is described in a companion paper by R.E. Toohey et al. The peripheral blood slides were prepared 1960-1965 during medical follow-up and were quite suitable for light microscope evaluation after 50+ years. PHA in neutrophils is characterized by oval, symmetric bilobed nuclei which are joined by a thin mitotic bridge. PHA is known to be caused by a decreased amount of the lamin B receptor (LBR). The B-type lamins are the building blocks of the cell’s nuclear lamina and the LBR gene is known to be located on the long arm of chromosome 1, 1q42.12. PHA expressed as a percentage of total neutrophils in this cohort rises in a nonlinear fashion over five decades of red marrow dose. Six subjects in this cohort eventually developed malignancies: five osteosarcomas and one mastoid cell neoplasm. The PHA percentage in these cases rises linearly with RBE-weighted red marrow dose (r2=0.71). No sarcomas are seen for RBE-weighted red marrow dose under 10,000 mGy-Eq (500 mGy). In the context of these experiments, Receiver Operating Curve (ROC) methodology may be used to evaluate the PHA% as a binary laboratory test to determine whether there is alpha dose to bone marrow. A cut-point of 5.74% PHA is found for identification of the dose category (AUC 0.961, sensitivity 97.8%, specificity 74.2%, PPV 94.3% for this dataset). PHA from peripheral blood is therefore a reasonable dose surrogate to evaluate alpha dose to bone marrow. Acknowledgements: this work was supported by the U.S. Department of Energy under contract number DE-AC05-06OR23100 with Oak Ridge Associated Universities and award number DE-HS0000073 to Washington State University.Recently the pseudo-Pelger Huët anomaly (PHA) in peripheral blood neutrophils was described as a new radiation-induced, stable biomarker (Goans et al. Health Phys 108(3), 2015). In this study, we have examined PHA in peripheral blood slides from a cohort of 166 former radium dial painters, 35 of whom had zero marrow dose. The slides were made available in collaboration with the US Transuranium and Uranium Registry (USTUR). Members of the radium dial painter cohort had ingestion of 226Ra and 228Ra at an early age (average age 20.6 ± 5.4 y; range 13-40 y) during the years 1914-1955. Exposure duration ranged from 1-1820 weeks with marrow dose 3-13,500 mGy-Eq. Red marrow alpha dosimetry for this study is described in a companion paper by R.E. Toohey et al. The peripheral blood slides were prepared 1960-1965 during medical follow-up and were quite suitable for light microscope evaluation after 50+ years. PHA in neutrophils is characterized by oval, symmetric bilobed nuclei which are joined by a thin mitotic bridge. PHA is known to be caused by a decreased amount of the lamin B receptor (LBR). The B-type lamins are the building blocks of the cell’s nuclear lamina and the LBR gene is known to be located on the long arm of chromosome 1, 1q42.12. PHA expressed as a percentage of total neutrophils in this cohort rises in a nonlinear fashion over five decades of red marrow dose. Six subjects in this cohort eventually developed malignancies: five osteosarcomas and one mastoid cell neoplasm. The PHA percentage in these cases rises linearly with RBE-weighted red marrow dose (r2=0.71). No sarcomas are seen for RBE-weighted red marrow dose under 10,000 mGy-Eq (500 mGy). In the context of these experiments, Receiver Operating Curve (ROC) methodology may be used to evaluate the PHA% as a binary laboratory test to determine whether there is alpha dose to bone marrow. A cut-point of 5.74% PHA is found for identification of the dose category (AUC 0.961, sensitivity 97.8%, specificity 74.2%, PPV 94.3% for this dataset). PHA from peripheral blood is therefore a reasonable dose surrogate to evaluate alpha dose to bone marrow. Acknowledgements: this work was supported by the U.S. Department of Energy under contract number DE-AC05-06OR23100 with Oak Ridge Associated Universities and award number DE-HS0000073 to Washington State University.

TPM-A.3   15:00  EURADOS Intercomparison on measurements of Am-241 in 3 skull phantoms MA LOPEZ*, CIEMAT, SPAIN ; P NOGUEIRA, HMGU, GERMANY; T VRBA, CTU-PRAGUE, CZECH REP.

Abstract: An international intercomparison action was organized by the Working Group 7 on Internal Dosimetry of European Radiation Dosimetry Group (EURADOS e.V. www.eurados.org) for the measurement of Americium in 3 skull phantoms using Ge detectors and gamma spectrometry. The exercise counted with the participation of 12 laboratories, 10 from Europe and 2 from North America. The main objectives were to compare the results of counting efficiency in fixed positions over each head phantom, the calculation of the activity of Americium in the skulls and to compare the phantoms it selves to check the best and appropriate features to be fulfilled by a calibration source representing the contamination of Americium in human head bone. The BfS skull was fabricated with real human bone artificially labelled with 241Am in its inner and outside sides and then covered with tissue-equivalent wax (Laurer G 1993). The BPAM phantom from USTUR (United States Transuranium and Uranium Registries) is part of the whole skeleton of a donor (USTUR Case No 102). In this case half of the skull was really contaminated due to an occupational intake of Americium by a U.S. worker, the other half is real human bone from non-contaminated person and the skull was covered by tissue equivalent material (G.S. Roessler, B. Magura. Health Physics. 49(4), 1985). Finally CSR phantom was fabricated as a simple hemisphere of equivalent bone and tissue material. The 3 phantoms differ in complexity, weight, size and shape which permitted a multi-parameter efficiency study. In case the participant counted with own calibration skull phantom, could use the laboratory calibration factor for the calculation of the activity in the 3 intercomparison phantoms. Results are discussed here. A Monte Carlo (MC) intercomparison was organized in parallel with the in-vivo monitoring exercise, using the voxel representations of the 3 physical phantoms. Three tasks were identified with increasing difficulty, starting with simple MC simulation of CSR hemisphere and the HMGU Ge detector for calculating the counting efficiency for the 59.54 keV photons of Am-241 in a predefined measurement geometry. Last step consisted in the MC simulation of the process of detection of each participant to calculate own calibration factor for his own detector system and counting geometry for a person monitoring. Conclusions of the exercise and difficulties found by the 16 participants in developing methodologies for Monte Carlo calibration are presented here.

TPM-A.4   15:45  The Importance of Plutonium Binding in Human Lungs A Birchall*, Global Dosimetry Ltd. , UK. ; M Puncher, Public Health England, UK; S Tolmachev, USTUR, Washington State University

Abstract: 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 ICRP biokinetic model, has been developed for such a 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 upper airways, this will double the lung dose. Furthermore, fb is very difficult to quantify from experimental measurements. This paper summarises the work carried out so far to quantify fb. Bayesian techniques have been used to analyse data from different sources, including both humans and dogs, and the results suggest a small, but non zero, 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 ICRP are currently considering the adoption of a value of 0.2% for the default bound fraction for all actinides, in the forthcoming recommendations on internal dosimetry. In an attempt to corroborate these findings, further experimental work has been carried out by the United States Transuranium and Uranium Registries (USTUR). This work has involved direct measurements of plutonium in the upper airways of workers who have been exposed to plutonium nitrate. Without binding, one would not expect to see any activity remaining in the upper airways at long times after exposure since it would have been cleared by the natural process of mucociliary clearance. Further supportive work on workers exposed to plutonium oxide is planned. This paper will ascertain to what extent these results corroborate the previous inferences concerning the bound fraction.

TPM-A.5   16:00  USTUR Case 0846: Modeling Americium Biokinetics after Intensive Decorporation Therapy B Breustedt*, KIT, Karlsruhe Institute of Technolgoy ; M Avtandilashvili, USTUR, Washington State University; SL McComish, USTUR, Washington State University; SY Tolmachev, USTUR, Washington State University

Abstract: One method to avert dose after incorporation of transuranium elements is decorporation therapy with chelating agents such as diethylenetriamine pentaacetate (DTPA). Administration of the therapeutic agent temporally enhances the excretion of the radionuclides. Biokinetic models, which describe the behavior of the radionuclides in the human body, need to be adapted to take into account the effect of the therapy. In this study, biokinetic modeling of decorporation therapy following americium oxide (241AmO2) inhalation was studied using USTUR Case 0846 (voluntary donor). The modeling of this case is a challenge given that the exact date of exposure is unknown. Previously, the case was evaluated using the assumption of chronic inhalation over a 2-year period. However, a possibility of acute intake cannot be dismissed. Initial 241Am whole-body deposition was estimated to be 66,600 Bq. The Registrant was extensively treated with Ca-DTPA over a period of 7 years. A total of 313.5 g DTPA was administered in 342 i.v. injections. At the time of death, 2,740 ±274 Bq of 241Am was measured in the lungs, 333 ±33 in the liver, and 19,570 ±1,957 in the skeleton by external gamma counting. Based on post-mortem radiochemical analysis results, 219.2 ±1.9 Bq and 29,600 ±195 Bq of 241Am were retained in the liver and the skeleton, respectively. For this study, a complete set of data including 106 fecal and 1,130 urine measurements was compiled. The CONRAD (Coordinated Network for Radiation Dosimetry) approach was applied to model americium decorporation using the excreta data only. Based on assumptions about the action and distribution of the administered DTPA, different modifications of the model were tested. To solve the compartmental model equations and fit the data, the ModelMaker4 and the SAAMII® software were used. To improve the modeling, tissue radiochemical analysis results were fitted simultaneously with the excretion data. The Bayesian approach was applied to characterize intake scenario and determine initial distribution of americium in the body prior to the therapy. This presentation provides preliminary results on americium biokinetic modeling after intensive decorporation treatment with Ca-DTPA.

TPM-A.6   16:15  Round Table with USTUR Former Directors

Abstract: Participants: Ron Kathren, Ron Filipy, Margery Swint; Bryce D. Breitenstein, Jim McInroy

TPM-A.7   16:45  Round Table open discussion



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