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.

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.

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.

Neutron Activated 153Sm Sealed in Carbon Nanocapsules for in Vivo Imaging and Tumor Radiotherapy.

Radiation therapy along with chemotherapy and surgery remain the main cancer treatments. Radiotherapy can be applied to patients externally (external beam radiotherapy) or internally (brachytherapy and radioisotope therapy). Previously, nanoencapsulation of radioactive crystals within carbon nanotubes, followed by end-closing, resulted in the formation of nanocapsules that allowed ultrasensitive imaging in healthy mice. Herein we report on the preparation of nanocapsules initially sealing "cold" isotopically enriched samarium (152Sm), which can then be activated on demand to their "hot" radioactive form (153Sm) by neutron irradiation. The use of "cold" isotopes avoids the need for radioactive facilities during the preparation of the nanocapsules, reduces radiation exposure to personnel, prevents the generation of nuclear waste, and evades the time constraints imposed by the decay of radionuclides. A very high specific radioactivity is achieved by neutron irradiation (up to 11.37 GBq/mg), making the "hot" nanocapsules useful not only for in vivo imaging but also therapeutically effective against lung cancer metastases after intravenous injection. The high in vivo stability of the radioactive payload, selective toxicity to cancerous tissues, and the elegant preparation method offer a paradigm for application of nanomaterials in radiotherapy.

RADIATION-INDUCED PLASMID DNA DAMAGE: EFFECT OF CONCENTRATION AND LENGTH.

Plasmid DNA is commonly used as a simpler substitute for a cell in studies of early effects of ionizing radiation because it allows to determine yields of primary DNA lesions. Experimental studies often employ plasmids of different lengths, in different concentrations in the aqueous solution. Influence of these parameters on the heavy-ion induced yields of primary DNA damage has been studied, using plasmids pUC19 (2686 bp), pBR322 (4361 bp) and pKLAC2 (9107 bp) in 10 and 50 ng/µl concentration. Results demonstrate the impact of plasmid length, while no significant difference was observed between the two concentrations. The uncertainty of the results is discussed.

Dosimetry as a Catch in Radiobiology Experiments.

Experimental radiobiological studies in which the effects of ionizing radiation on a biological model are examined often highlight the biological aspects while missing detailed descriptions of the geometry, sample and dosimetric methods used. Such omissions can hinder the reproducibility and comparability of the experimental data. An application based on the Geant4 simulation toolkit was developed to design experiments using a biological solution placed in a microtube. The application was used to demonstrate the influence of the type of microtube, sample volume and energy of a proton source on the dose distribution across the sample, and on the mean dose in the whole sample. The results shown here are for samples represented by liquid water in the 0.4-, 1.5- and 2.0-ml microtubes irradiated with 20, 30 and 100 MeV proton beams. The results of this work demonstrate that the mean dose and homogeneity of the dose distribution within the sample strongly depend on all three parameters. Furthermore, this work shows how the dose uncertainty propagates into the scored primary DNA damages in plasmid DNA studies using agarose gel electrophoresis. This application is provided freely to assist users in verifying their experimental setup prior to the experiment.

Technical Note: Impact of cell repopulation and radionuclide uptake phase on cell survival.

PURPOSE: To study theoretically the impact on cell survival of the radionuclide uptake rate inside tumor cells for a single administration of a radiopharmaceutical. METHODS: The instantaneous-uptake model of O'Donoghue ["The impact of tumor cell proliferation in radioimmunotherapy," Cancer 73, 974-980 (1994)] for a proliferating cell population irradiated by an exponentially decreasing dose-rate is here extended to allow for the monoexponential uptake of the radiopharmaceutical by the targeted cells. The time derivative of the survival curve is studied in detail deducing an expression for the minimum of the surviving fraction and the biologically effective dose (BED). RESULTS: Surviving fractions are calculated over a parameter range that is clinically relevant and broad enough to establish general trends. Specifically, results are presented for the therapy radionuclides Y-90, I-131, and P-32, assuming uptake half-times 1-24 h, extrapolated initial dose-rates 0.5-1 Gy h(-1), and a biological clearance half-life of seven days. Representative radiobiological parameters for radiosensitive and rapidly proliferating tumor cells are used, with cell doubling time equal to 2 days and α-coefficient equal to 0.3 and 0.5 Gy(-1). It is shown that neglecting the uptake phase of the radiopharmaceutical (i.e., assuming instantaneous-uptake) results in a sizeable over-estimation of cell-kill (i.e., under-estimation of cell survival) even for uptake half-times of only a few hours. The differences between the exponential-uptake model and the instantaneous-uptake model become larger for high peak dose-rates, slow uptakes, and (slightly) for long-lived radionuclides. Moreover, the sensitivity of the survival curve on the uptake model was found to be higher for the tumor cells with the larger α-coefficient. CONCLUSIONS: The exponential-uptake rate of the radiopharmaceutical inside targeted cells appears to have a considerable effect on the survival of a proliferating cell population and might need to be considered in radiobiological models of tumor cell-kill in radionuclide therapy.

Calculation of cellular S-values using Geant4-DNA: The effect of cell geometry.

PURPOSE: Geant4-DNA is used to calculate S-values for different subcellular distributions of low-energy electron sources in various cell geometries. METHOD: Calculations of cellular S-values for monoenergetic electron sources with energy from 1 to 100 keV and the Auger-electron emitting radionuclides Tc-99m, In-111, and I-125 have been made using the Geant4 Monte Carlo toolkit. The Geant4-DNA low-energy extension is employed for simulating collision-by-collision the complete slowing-down of electron tracks (down to 8 eV) in liquid water, used as a surrogate of human cells. The effect of cell geometry on S-values is examined by simulating electron tracks within different cell geometries, namely, a spherical, two ellipsoidal, and an irregular shape, all having equal cellular and nuclear volumes. Algorithms for randomly sampling the volume of the nucleus, cytoplasm, surface, and whole cell for each cell phantom are presented. RESULTS: Differences between Geant4-DNA and MIRD database up to 50% were found, although, for the present radionuclides, they mostly remain below 10%. For most source-target combinations the S-values for the spherical cell geometry were found to be within 20% of those for the ellipsoidal cell geometries, with a maximum deviation of 32%. Differences between the spherical and irregular geometries are generally larger reaching 100-300%. Most sensitive to the cell geometry is the absorbed dose to the nucleus when the source is localized on the cell surface. Interestingly, two published AAPM spectra for I-125 yield noticeable differences (up to 19%) in cellular S-values. CONCLUSION: Monte Carlo simulations of cellular S-values with Geant4-DNA reveal that, for the examined radionuclides, the widely used approximation of spherical cells is reasonably accurate (within 20-30%) even for ellipsoidal geometries. For irregular cell geometries the spherical approximation should be used with caution because, as in the present example, it may lead to erroneous results for the nuclear dose for the commonly encountered situation where the source is localized to the cell surface.