Identification of Volume of Distribution for 239Pu in Rats.

ABSTRACT: The work within identifies the volume of distribution (VD) of plutonium using data from studies in which rats were administered an intravenous bolus injection of 239Pu4+-citrate. The research investigated two separate datasets. Data published by Durbin and colleagues in "Plutonium Deposition Kinetics in Rats" and studies conducted by Lovelace Respiratory Research Institute (LRRI) were examined. The goal of this research was to identify a value of VD consistent with the known biological behavior of plutonium. The identified VD is necessary to develop a physiologically-based pharmacokinetic (PBPK) model. The creation of a PBPK model describing the behavior of plutonium in the body enables the comparison of transfer rates to validate the biokinetic models currently in use for internal dosimetry purposes. The VD of a substance describes the distribution between intracellular and extracellular fluid compartments, providing information such as cellular uptake and protein binding. The VD time profiles and values found using the Durbin data were consistent with known behavior of plutonium. The VD values found using data provided by LRRI were not consistent with known behavior of plutonium; however, the VD time profiles generated may still be of use for PBPK modeling.

Optimization of the ICRP 67 and NCRP 156 Transfer Rates Applied to Nonhuman Primates Intramuscularly Injected With 241Am.

Nonhuman primates intramuscularly injected with Am have been investigated using the International Commission on Radiological Protection Report 67 model coupled with National Council on Radiation Protection and Measurements Report 156 model. Default parameters from these models were input into the Integrated Modules for Bioassay Analysis software to predict the intake and skeleton retention in 20 tested nonhuman primates. The predictions generated were compared to the experimental data from the Durbin nonhuman primate studies. A previous study conducted by Alomairy in 2017 indicated that the early behavior of Am(NO3)3 in wound cases can be explained using the default transfer rates. However, these transfer rates were not able to predict the intake and skeleton retention at the time of sacrifice after 100 d postintake due to differences in the amount of activity translocated or deposited in liver tissue and nonliver tissues (primarily skeleton). This is likely due to the physiological differences between the nonhuman primate and human. The objective of this study was to develop new transfer rate parameters for wound and systemic models in an effort to improve biokinetic predictions. Estimates of new transfer rates appropriate for nonhuman primate data were estimated by employing a companion software program called Integrated Modules for Bioassay Analysis Uncertainty Analyzer. During validation of the suggested transfer rates, it was observed that the optimized parameters predicted the intake in 66% of the tested animals used in this investigation. The activity retained in the skeleton improved in almost all cases where the differences between predicted and measured activity is less than 20%.

Application of the ICRP 67 and NCRP 156 Biokinetic Models to 241 Am Wound Data from Nonhuman Primates.

Distribution, retention, and excretion of intramuscularly injected Am citrate have been investigated in cynomolgus and rhesus nonhuman primates (NHP). Bioassay and retention data, obtained from experiments done by Patricia Durbin and her colleagues at Lawrence Berkeley National Laboratory, were evaluated against the International Commission on Radiological Protection (ICRP 67) Am systemic model coupled with to the National Council on Radiation Protection and Measurement wound model (NCRP 156). The default transfer rates suggested in these models were used with the urine and feces excretion data to predict the intake as well as liver and skeleton tissue contents at the time of death. The default models adequately predict the animals' urine bioassay data, but the injected activities were overpredicted by as much 4.41 times and underpredicted by as much as 0.99 times. Poor prediction has been observed in all cases using fecal excretion. The retained activity in the liver and skeleton were investigated using the same approach. It appears that the models predict the amount of the activity retention in the skeleton more accurately than in the liver. The fraction of predicted to measured activity at the time of death in the skeleton was over 1.0 in most cases, and accurate predictions were obtained in seven cases. The predicted activity in skeleton for these cases ranged from 2.7 to 17% overestimated activity and from 9 to 14% underestimated activity. NHPs' urine data and organ retention were compared with data from previously modeled baboons and beagle dogs. About 6% of the injected activity in baboons and beagle dog was excreted in urine and approximately 0.1% in feces in the first 24 h. The results from NHP are not different from excreta analysis in these other species. Urinary excretion in the cynomolgus, rhesus, and baboon NHP is the dominant pathway of Am clearance; however, fecal excretion is considered dominant in beagle dogs. The comparison between NHPs and humans is difficult due to the differences in the number of activities translocated or deposited in the liver tissue and nonliver tissues (primarily skeleton), in addition to the physiological differences between the NHPs and humans.

A Case Study of the NCRP 156 Wound Model of Embedded DU Using Data From Urine Uranium Concentrations of Wounded Veterans.

Depleted uranium (DU) munitions were initially used by the United States (U.S.) military during the first Persian Gulf War in 1991 in order to penetrate heavily armored vehicles. However, as a result of friendly fire, several U.S. military personnel received intakes from DU munitions. One of the ongoing concerns for these wounded veterans is the potential long-term exposure received from DU embedded fragments. The United States Army Institute of Public Health (AIPH) is the first laboratory that analyzes the urine bioassays from Army Soldiers that are injured with DU fragments. The United States Air Force School of Aerospace Medicine also evaluates bioassays from DU injuries. The urine bioassay data collected by AIPH was evaluated using the NCRP 156 wound model coefficients for the DU-Wafer, Fragment, and Particle models. The maximum likelihood method was used in the Integrated Modules for Bioassay Analysis (IMBA-PPAE) to calculate the estimates of intake and tissue doses. Evaluating the three models for wound retention, the DU-Wafer and Fragment model yielded a credible fit to the bioassay data. Comparing the two models, the DU-Wafer model fits the data better than the Fragment model when comparing their autocorrelation coefficient and chi-squared values of (P 1.73 × 10, c 4.83 × 10), (P 2.01 × 10, c 1.09), respectively. This evaluation supports the validity of both the DU-wafer model as well as the default fragmentation model proposed by NCRP 156.

Investigating Uranium Isotopic Ratios and Activity Ratios in Groundwaters in the State of Idaho.

Analyzing uranium isotopic and activity ratios can give valuable information for hydrologic and environmental studies such as insights to weathering processes, estimating water mixing ratios, and identifying water sources. The authors employed an inductively coupled plasma mass spectrometer (ICP-MS) to perform environmental level concentration measurements of isotopic uranium on 380 groundwater samples from various locations within the state of Idaho. The U:U uranium activity ratios (UAR) for these samples range between 0.91 and 6.21, which suggests that the parent U is not in equilibrium with its decay product U. The U:U isotopic ratio was also measured for each sample to confirm that there was no depleted or enriched uranium present. All 380 samples exhibited the natural isotopic ratios of U and U isotopes. Therefore, it was concluded that the U:U UARs reflect natural variations in the Idaho groundwater systems.

Plasma Retention and Systemic Kinetics of 90Sr Intramuscularly Injected in Female Nonhuman Primates.

Thirteen female Rhesus macaques were intramuscularly injected with Sr(NO3)2 diluted in sodium citrate solution. The biokinetic data from these animals were compared against the predictions of the NCRP 156 wound models combined with the ICRP systemic models. It was observed that the activities measured in plasma of these nonhuman primates (NHPs) were consistently lower than those predicted by the default human biokinetic models. The urinary excretion from the NHPs at times immediately after injection was much greater than that in humans. The fecal excretion rates were found to be in relatively better agreement with humans. Similarly, the activities retained in the skeleton of the NHPs were lower than those in humans. These differences were attributed to the higher calcium diet of the NHPs (0.03 to 0.12 g d kg body weight) compared to that of humans. These observations were consistent with the early animal and human studies that showed the effect of calcium on strontium metabolism, specifically urinary excretion. Strontium is preferentially filtered at a much higher rate in kidneys than calcium because it is less completely bound to protein than is calcium. These differences, along with large inter-animal variability, should be considered when estimating the behavior of strontium in humans from the metabolic data in animals or vice versa.

Behavior of Americium in Simulated Wounds in Nonhuman Primates.

An americium solution injected intramuscularly into several nonhuman primates (NHPs) was found to behave differently than predicted by the wound models described in the NCRP Report 156. This was because the injection was made along with a citrate solution, which is known to be more soluble than chlorides, oxides, or nitrates on which the NCRP Report was based. A multi-exponential wound model specific to the injected americium solution was developed based on the retention in the intramuscular sites. The model was coupled with the americium systemic model to interpret the urinary excretion data and assess the intake, and it was determined that the models were adequate to predict early urinary excretion in most cases but unable to predict late urinary excretion. This was attributed to the differences in the systemic handling of americium between humans and nonhuman primates. Information on the type of wounds, solubility, particle size, mass, chemical form, etc., should always be considered when performing wound dosimetry.

ICRP 67 Biokinetic Models for AM-241 Applied to Nonhuman Primates.

Between 1960 and 1985, Patricia Durbin and colleagues performed studies on the distribution of intravenously and intramuscularly injected Am citrate with dosages ranging from 16 to 32 kBq kg in 30 male and female non-human primates (NHP). Dr. Durbin died unexpectedly in March of 2009, leaving much of the extensive serial blood, bioassay, and autopsy data from these NHP studies unanalyzed. As part of the experimental design, serial blood samples were taken, and urine and feces samples were collected separately for the duration of the study. The measurements of urine, fecal excretion, blood samples, and organ burden data obtained from the animals were used to evaluate the transfer rates of the ICRP 67 biokinetic model for Am. Seven cases, in which the primates were administered Am citrate by intravenous injection, were evaluated using the ICRP 67 systemic model. There were differences ranging from 51.4% underestimated to 102.7% overestimated activity between the predicted intake, which was calculated using IMBA Professional Plus software and based upon the urine bioassay data and the actual activity. The difference between the predicted activity at the time of death in the liver and skeleton using IMBA professional software and the value of the measured activity at the time of death were also compared. Generally, the ratios of predicted activity in the liver and skeleton at the time of death to the measured activity were consistently more than 1. However, the ratios were less than 1 in the skeleton for animals that were sacrificed 2,199 and 973 d post injection. The posterior probability distributions for model parameters derived using WeLMoS method were inconsistent with the ICRP 67 default parameters. The prediction made based on the posterior probability distributions for model parameters derived using WeLMoS gave the best fit to these data; however, the modified parameters overestimated the activity in almost all cases. The difference between the predicted Am activity and the value of the measured activity may be due to the physiological age-related characteristics relative to the age of the animal at the time of the injection and early and long scarified time.

Investigating Uranium Concentrations in Groundwaters in the State of Idaho Using Kinetic Phosphorescence Analysis and Inductively Coupled Plasma Mass Spectrometry.

The determination of uranium concentrations in natural water samples is of great interest due to the environmental consequences of this radionuclide. In this study, 380 groundwater samples from various locations within the state of Idaho were analyzed using two different techniques. The first method was Kinetic Phosphorescence Analysis (KPA), which gives the total uranium concentrations in water samples. The second analysis method was inductively coupled plasma mass spectrometry (ICP- MS). This method determines the total uranium concentration as well as the separate isotope concentrations of uranium. The U/U isotopic ratio was also measured for each sample to confirm that there was no depleted or enriched uranium present. The results were compared and mapped separately from each other. The study also found that in some areas of the state, natural uranium concentrations are relatively high.

Biokinetics of Plutonium in Nonhuman Primates.

A major source of data on metabolism, excretion and retention of plutonium comes from experimental animal studies. Although old world monkeys are one of the closest living relatives to humans, certain physiological differences do exist between these nonhuman primates and humans. The objective of this paper was to describe the metabolism of plutonium in nonhuman primates using the bioassay and retention data obtained from macaque monkeys injected with plutonium citrate. A biokinetic model for nonhuman primates was developed by adapting the basic model structure and adapting the transfer rates described for metabolism of plutonium in adult humans. Significant changes to the parameters were necessary to explain the shorter retention of plutonium in liver and skeleton of the nonhuman primates, differences in liver to bone partitioning ratio, and significantly higher excretion of plutonium in feces compared to that in humans.

Application of NCRP 156 Wound Model and ICRP 67 Systemic Plutonium Model for Analysis of Urine Data from Simulated Wounds in Nonhuman Primates.

The predictions of the wound model described in NCRP Report No. 156, coupled with the systemic model described in ICRP 67, were compared with the actual urinary excretion data and wound retention data from nonhuman primates injected intramuscularly or subcutaneously with Pu(IV) citrate. The results indicated that the early behavior of Pu(IV) citrate in wounds can be adequately described by the default retention parameters for moderately retained radionuclides suggested by the report. The urinary excretion rates after 200 d post intake could not be described well by the parameters of any of the default wound models because of the differences in the systemic handling of plutonium by humans compared to nonhuman primates.

Biokinetics of 90Sr in Male Nonhuman Primates.

The current study tests the hypothesis that the biokinetics of Sr can be represented by simplification of the ICRP publication 78 Sr model. Default and proposed models were evaluated by their ability to predict injected activity and more thoroughly define the activity residing in the skeleton of rhesus monkeys. The data obtained from studies done by Patricia Durbin and her colleagues at the Lawrence Berkley National Laboratory were used to create a profile of the activity residing in the skeleton at the time of sacrifice. Post mortem data along with periodic whole body count data were used to optimize the biokinetic parameters using the Integrated Modules for Bioassay Analysis (IMBA), Weighted Likelihood Monte-Carlo Sampling (WeLMoS) program to better predict the intake and fit of the bioassay data. Analysis of the default ICRP 78 parameters resulted in an overprediction of activity in the skeleton for a male cohort by as much as 180%. Using Monte Carlo sampling methods, three models were developed and optimized for a composite cohort of male monkeys. Of the three developed models, one model proved to have the best predictive capabilities. The optimized model C obtained for the male cohort was then tested on a validation cohort to test predictive capabilities. Using the optimized model C parameters, the ability to predict activity in the skeleton was improved in comparison to ICRP 78. Prediction of the intake from bioassay data was also improved by a factor of 2 in comparison to ICRP 78. The results suggest that the modified transfer rates of model C could be used as default parameters for biokinetic nonhuman primate modeling and potentially extrapolated to humans.

Strontium-90 Biokinetics from Simulated Wound Intakes in Non-human Primates Compared with Combined Model Predictions from National Council on Radiation Protection and Measurements Report 156 and International Commission on Radiological Protection Publication 67.

This study had a goal to evaluate the predictive capabilities of the National Council on Radiation Protection and Measurements (NCRP) wound model coupled to the International Commission on Radiological Protection (ICRP) systemic model for 90Sr-contaminated wounds using non-human primate data. Studies were conducted on 13 macaque (Macaca mulatta) monkeys, each receiving one-time intramuscular injections of 90Sr solution. Urine and feces samples were collected up to 28 d post-injection and analyzed for 90Sr activity. Integrated Modules for Bioassay Analysis (IMBA) software was configured with default NCRP and ICRP model transfer coefficients to calculate predicted 90Sr intake via the wound based on the radioactivity measured in bioassay samples. The default parameters of the combined models produced adequate fits of the bioassay data, but maximum likelihood predictions of intake were overestimated by a factor of 1.0 to 2.9 when bioassay data were used as predictors. Skeletal retention was also over-predicted, suggesting an underestimation of the excretion fraction. Bayesian statistics and Monte Carlo sampling were applied using IMBA to vary the default parameters, producing updated transfer coefficients for individual monkeys that improved model fit and predicted intake and skeletal retention. The geometric means of the optimized transfer rates for the 11 cases were computed, and these optimized sample population parameters were tested on two independent monkey cases and on the 11 monkeys from which the optimized parameters were derived. The optimized model parameters did not improve the model fit in most cases, and the predicted skeletal activity produced improvements in three of the 11 cases. The optimized parameters improved the predicted intake in all cases but still over-predicted the intake by an average of 50%. The results suggest that the modified transfer rates were not always an improvement over the default NCRP and ICRP model values.

Particle size characterization of aerosols generated during surface contaminated concrete demolition.

The purpose of this study was to measure mass and activity distributions from the aerosols generated during the demolition of surface contaminated concrete. Air samples were collected using a cascade impactor during the mechanical hammering and dismantlement of radiologically contaminated high level waste process vaults from which the piping and components had been previously removed. The experimentally determined distribution parameters were compared with the 5.0-µm particle size referenced in the U.S. Department of Energy (U.S. DOE) regulations pertaining to internal deposition (10CFR835 and ICRP66). Mass distribution parameters were compared with their activity distribution counterparts. The Mass Median Aerodynamic Diameter (MMAD) was determined to be 4.2 µm with a Mass Geometric Standard Deviation (GSDM) of 2.3 µm, and the Co Activity Median Aerodynamic Diameter (AMAD) was determined to be 3.9 µm with an Activity Geometric Standard Deviation (GSDA) of 2.3 µm. These results are consistent with the ICRP66 5.0-µm reference particle size and the Derived Air Concentration (DAC) values referenced in 10CFR835 and utilized throughout the U.S. DOE complex.

Monte Carlo simulation of in vivo measurement of the most suitable knee position for the optimal measurement of activity.

A new computational model has been developed using the Monte Carlo (MC) technique to simulate in vivo measurements with the objective of understanding the most precise measurement location with respect to quantifying the activity of Am in the bones. To benchmark the model, in vivo measurements were performed on the U.S. Transuranium and Uranium Registries (USTUR) case 0846 leg. Front and lateral measurements of the knee of the USTUR case 0846 leg in a bent position and the same measurements with the leg in a straight position using a HP(Ge) detector were completed. Experimental results concluded that the front measurement of the knee in a bent leg position gave the highest count rate, which is an indication of optimal detection efficiency. Therefore, this geometry and knee-detector position were considered as the most appropriate position for knee monitoring. A computational model using MCNPX version 2.6.0 was used to simulate the experimental measurements by using a leg voxel phantom. The mean value and standard deviation (SD) of peak efficiency due to an isotropic 59.5-keV photon from Am were calculated in four different counting geometries. An extra sum of squares F-test was performed on the mean values of the simulated detection efficiencies. The p-value obtained from this statistical test indicates that the differences among the mean values for different counting geometries were significant. These results suggest that the front measurement of a knee in a bent leg position is the optimal counting geometry for in vivo measurement of Am deposited in the bones. The computational model was validated through comparison of the measured and simulated detection efficiencies. It was observed that there is no difference at the 0.1 significant levels between the simulated and measured detection efficiencies in assessment of Am within the bones.

Contamination analysis of radioactive samples in focused ion beam instruments.

The use of Focused Ion Beam (FIB) instrument's to analyze and prepare samples that are radioactive requires attentiveness to the materials that are dislodged and free inside the chamber. Radioactive sputtered material must be understood even when observed at trace concentrations. Measurements using liquid scintillation counting and high purity germanium detectors were used to evaluate contamination on accessible surfaces inside a focused ion beam chamber that was used in the preparation of samples that were radioactive. The maximum removable contamination found was 0.27 0.4 Bq cm(-2), on the focused ion beam wall with 0.24 0.019 Bq cm(-2) on the door. Although these magnitudes of removable contamination are inconsequential for activation products, these same magnitudes of actinides, for example 239Pu, would represent 3.2% of an Annual Limit of Intake. This might be considered significant if one examines the relatively infrequent use of this device for the preparation of radioactive samples. Predicted activities of sputtered material were found using the software Transport of Ions in Matter, estimating that 0.003% of a radioactive samples activity is released into the FIB chamber. A used secondary electron detector's activity was measured to be 383.7 8.1 Bq. Preferential build-up of sputtered materials due to temperature or static charge gradients was considered. No temperature gradients were observed. Static charge gradients were measured inside the chamber varying between 0.057% below the mean to 34% higher than the mean. However, the magnitudes of contamination measured did not correlate to static charge gradients. Deposition in the chamber appears to have no mechanical cause but rather is sporadic however, measureable. Experience to date has been limited to samples of low activity; nevertheless, contamination inside the chamber was observed. Users should anticipate higher levels of readily dispersible radioactive contamination within the FIB as sample activity increases.

Reevaluation of (241)Am content in the USTUR case 0102 leg phantom.

The (241)Am contents in the United States Transuranium and Uranium Registries' (USTUR) case 0102 leg phantom were previously estimated to be 1,243 ± 11 Bq. Recent analysis of the computed tomography images of the phantom revealed multiple bone structures missing from various regions of the phantom skeleton including: posterior ilium, anterior ilium, ischium, femur proximal end, femur middle shaft, femur distal end, patella, tibia distal shaft, fibula distal shaft, and fibula distal end. Additionally, the fifth metatarsal and all of the fifth-digit phalanges were found to be completely missing from the foot. A three-dimensional (3D) model of the leg phantom was created using 3D-Doctor software. Volumes of missing bone structures were outlined separately based on the anatomical assessment of those structures. Weights of the missing bone samples were calculated. Consequently, the value of total( 241)Am activity in the USTUR leg phantom is 1,218 ± 11 Bq. This activity is about 2.0% less than the previously published value of 1,243 ± 11 Bq. External gamma detector response was simulated considering both activity values (1,243 and 1,218 Bq) across the five different locations along the USTUR leg phantom: foot, middle leg, knee, middle thigh, and hip. Each counting position was chosen such that it was above the missing bone structure locations. The highest difference observed between the two counting efficiencies (each corresponding to the two different quantities of estimated activity) was 8.2% and 9.4% for locations above the foot and middle thigh, respectively. Other counting locations (middle leg, knee, and hip) showed efficiency variations of about 1%.

A new leg voxel model in two different positions for simulation of the non-uniform distribution of (241)Am in leg bones.

A new leg voxel model in two different positions (straight and bent) has been developed for in vivo measurement calibration purposes. This voxel phantom is a representation of a human leg that may provide a substantial enhancement to Monte Carlo modeling because it more accurately models different geometric leg positions and the non-uniform distribution of Am throughout the leg bones instead of assuming a one-position geometry and a uniform distribution of radionuclides. This was accomplished by performing a radiochemical analysis on small sections of the leg bones from the U.S. Transuranium and Uranium Registries (USTUR) case 0846. USTUR case 0846 represents an individual who was repeatedly contaminated by Am via chronic inhalation. To construct the voxel model, high resolution (2 mm) computed tomography (CT) images of the USTUR case 0846 leg were obtained in different positions. Thirty-six (36) objects (universes) were segmented manually from the CT images using 3D-Doctor software. Bones were divided into 30 small sections with an assigned weight exactly equal to the weight of bone sections obtained from radiochemical analysis of the USTUR case 0846 leg. The segmented images were then converted into a boundary file, and the Human Monitoring Laboratory (HML) voxelizer was used to convert the boundary file into the leg voxel phantom. Excluding the surrounding air regions, the straight leg phantom consists of 592,023 voxels, while the bent leg consists of 337,567 voxels. The resulting leg voxel model is now ready for use as an MCNPX input file to simulate in vivo measurement of bone-seeking radionuclides.

Evaluation of (241)Am deposited in different parts of the leg bones and skeleton to justify in vivo measurements of the knee for estimating total skeletal activity.

The percentage of Am deposited in different parts of leg bones relative to the total leg activity was calculated from radiochemical analysis results from six whole body donors participating in the U.S. Transuranium and Uranium Registries (USTUR). In five of these six USTUR cases, the percentage of Am deposited in the knee region as well as in the entire leg was separately calculated relative to total skeletal activity. The purpose of this study is to find a region in the leg that is both suitable for in vivo measurement of Am deposited in the bones and has a good correlation with the total skeletal Am burden. In all analyzed cases, the femur was the bone with the highest percentage of Am deposited in the leg (48.8%). In the five cases that have complete whole skeletal analysis, the percentage of Am activity in the knee relative to entire skeletal activity was 4.8%, and the average value of its coefficient of variation was 10.6%. The percentage of Am in the leg relative to total skeletal activity was 20% with an average coefficient of variation of 13.63%. The Am activity in the knee as well as in the leg was strongly correlated (R = 99.5% and R = 99.1%, respectively) with the amount of Am activity in the entire skeleton using a simple linear relationship. The highest correlation was found between the amount of Am deposited in the knee and the amount of Am deposited in the entire skeleton. This correlation is important because it might enable an accurate assessment of the total skeletal Am burden to be performed from in vivo monitoring of the knee region. In all analyzed cases, an excellent correlation (R = 99.9%) was found between the amount of Am activity in the knee and the amount of Am activity in the entire leg. The results of this study suggest three simple models: two models to predict the total skeletal activity based on either leg or knee activity, and the third model to predict the total leg activity based on knee activity. The results also suggest that the knee region is a suitable position for in vivo measurements of Am deposited in the bones and also for an accurate and efficient detection system. Detector efficiency should be apparently calibrated based on only the Am burden in the knee region bones instead of Am activity deposited in the entire leg.

Effect of a Simulation of 241Am Deposition Pattern in the Leg Bones on the Detection Efficiency of a High Purity Germanium Detector.

A computational model using an MCNPX version 2.6.0 code and a leg voxel phantom was previously constructed and validated against the in vivo measurements of the United States Transuranium and Uranium Registries (USTUR) case 0846 leg. Using the MCNPX model, different simulation scenarios of Am distribution in the bones and tissue material of a leg were performed, and their effects on the detection efficiency and activity calculation were examined. The purpose of this work is to ensure and increase the simulation sensitivity of real contaminated human bones and reduce the simulated efficiency error associated with the distribution of Am activity within the leg bones when using a high purity germanium [HP(Ge)] detector. The results showed that the simulated detection efficiency obtained from the uniform distribution of Am in the leg bones was underestimated by a factor of up to 0.3 compared with the measured and simulated detection efficiency obtained from the non-uniform distribution of Am in different sections of the leg bones. The p-value of a one-way analysis of variance (ANOVA) F-test among the mean values of the simulated detection efficiencies was calculated and provided evidence of a significant difference. The uncertainty in the bone activity estimate could be quite large (25% to 30%) if calibration of detection efficiency is based on assuming a uniform distribution of Am in the phantom to estimate the USTUR case 0846 leg activity. It is therefore recommended that during calibration of detectors, a non-uniform distribution of Am in different sections of the bones should be used rather than a uniform distribution. Additionally, an assumption of a uniform distribution of Am will simulate Am activity deposited in the leg bones of a real contamination case inadequately.