Nitrogen isotopic composition as a gauge of tumor cell anabolism-to-catabolism ratio.

Studies have suggested that cancerous tissue has a lower 15N/14N ratio than benign tissue. However, human data have been inconclusive, possibly due to constraints on experimental design. Here, we used high-sensitivity nitrogen isotope methods to assess the 15N/14N ratio of human breast, lung, and kidney cancer tissue at unprecedented spatial resolution. In lung, breast, and urothelial carcinoma, 15N/14N was negatively correlated with tumor cell density. The magnitude of 15N depletion for a given tumor cell density was consistent across different types of lung cancer, ductal in situ and invasive breast carcinoma, and urothelial carcinoma, suggesting similar elevations in the anabolism-to-catabolism ratio. However, tumor 15N depletion was higher in a more aggressive metaplastic breast carcinoma. These findings may indicate the ability of certain cancers to more effectively channel N towards growth. Our results support 15N/14N analysis as a potential tool for screening biopsies and assessing N metabolism in tumor cells.

Passive Sampling Tool for Actinides in Spent Nuclear Fuel Pools.

Spent nuclear fuel must be carefully managed to prevent pollution of the environment with radionuclides. Within the framework of correct radioactive waste management, spent fuel rods are stored in cooling pools to allow short-lived fission products to decay. If fuel rods leak, they liberate radionuclides into the cooling water; therefore, it is essential to determine radionuclide concentrations in the pool water for monitoring purposes and to plan the decommissioning process. In this work, we present, to our knowledge, the first passive sampling technique for measures of actinides in spent nuclear fuel pools, based on recently developed diffusive gradients in thin-film (DGT) configurations. These samplers eliminate the need to retrieve and handle large samples of fuel pool water for radiochemical processing by immobilizing their targeted radionuclides in situ on the solid phase within the sampler. This is additionally the first application of the DGT technique for Cm measure. Herein, we make the calibrated effective diffusion coefficients of U, Pu, Am, and Cm in borated spent fuel pool water available. We tested these samplers in the fuel pool of a nuclear facility and measured samples using accelerator mass spectrometry to provide high-precision isotopic reports, allowing for the first independent implementation of a recently developed technique for dating nuclear fuel based on its Cm isotope signature.

Solid-phase extraction of 225Ac using ion-imprinted resin and 243Am as a radioactive tracer for internal dosimetry and incorporation measurements.

Actinium-225 is a highly radiotoxic alpha-emitting radionuclide, which is currently in the spotlight owing to its promising radiotherapeutic applications in nuclear medicine. Personnel involved in the production and handling of actinium-225 is exposed to a risk of accidental incorporation of this radionuclide. Radiological protection regulations require regular monitoring of incorporation and internal dosimetry assessment for workers manipulating open radioactive sources. Urine is often used as a biological sample for measuring the incorporation of actinides, however it requires a radiochemical separation with a certified metrological tracer to enable quantitative determination. There is no stable, nor sufficiently long-lived radioactive isotopes of actinium to provide a metrological yield tracer. In this article, we propose an application of an ion-imprinted polymer resin to extract actinium-225 from urine employing americium-243 as a radioactive tracer. The radiochemical separation was followed by a quantitative determination with alpha-spectrometry. Solid-phase extraction of both actinides from urine using ion-imprinted polymer resin resulted in good radiochemical yields: 57.7 ± 16.5% (n = 17) for actinium-225 and 62.8 ± 18.0% (n = 17) for americium-243. Equivalent recoveries showed that americium-243 is a suitable yield tracer for the determination of actinium-225 with an ion-imprinted polymer resin. Combined with a different measurement technique, this method can be applied for the separation of other isotopes of actinium, such as actinium-227.

Uranium stability in a large wetland soil core probed by electron acceptors, carbonate amendments and wet-dry cycling in a long-term lysimeter experiment.

Understanding the hydro-biogeochemical conditions that impact the mobility of uranium (U) in natural or artificial wetlands is essential for the management of contaminated environments. Field-based research indicates that high organic matter content and saturation of the soil from the water table create favorable conditions for U accumulation. Despite the installation of artificial wetlands for U remediation, the processes that can release U from wetland soils to underlying aquifers are poorly understood. Here we used a large soil core from a montane wetland in a 6 year lysimeter experiment to study the stability of U accumulated to levels of up to 6000 ppm. Amendments with electron acceptors showed that the wetland soil can reduce sulfate and Fe(III) in large amounts without significant release of U into the soil pore water. However, amendment with carbonate (5 mM, pH 7.5) resulted in a large discharge of U. After a six-month period of imposed drought, the re-flooding of the core led to the release of negligible amounts of U into the pore water. This long-term experiment demonstrates that U is strongly bound to organic matter and that its stability is only challenged by carbonate complexation.

An investigation of aspects of radiochemical purity of 99mTc-labelled human serum albumin nanocolloid.

BACKGROUND: Nanocolloidal human serum albumin radiolabelled with 99mTc provides a diagnostic radiopharmaceutical for sentinel node lymphoscintigraphy. NanoHSA (Nanotop), a commercially available kit, enables the simple preparation of this radiopharmaceutical via reconstitution with pertechnetate eluted from a generator. Thin-layer chromatography is widely used for determining radiochemical purity in clinical nuclear medicine. Quality control methods recommended by the manufacturer were sometimes reported to yield variable results. Therefore, we proposed and evaluated three alternative thin-layer chromatography methods for the quality control of [99mTc]Tc-NanoHSA from a commercially available kit. RESULTS: The radiochemical purity of [99mTc]Tc-NanoHSA determined with all methods was reproducible and met the requirements of the SPC and the European Pharmacopoeia (≥ 95%). Our quality control using iTLC-SG chromatographic paper in methyl ethyl ketone mobile phase identified only free pertechnetate as impurity, resulting in > 99% RCP. The quality control using iTLC-SG in 85% methanol or iTLC-SA in 0.9% NaCl identified an additional small fraction of a hydrophilic impurity, resulting in 95-97% RCP. Glucose was identified as a potential 99mTc-carrying hydrophilic species contributing to hydrophilic impurities. CONCLUSION: Our quality control of [99mTc]Tc-NanoHSA with non-polar mobile phase tended to underestimate the amount of hydrophilic impurities, although without compromising the final quality of the radiopharmaceutical. Alternative TLC methods using aqueous mobile phases enabled a more accurate determination of hydrophilic impurities.

Radionuclides in the Environment in Switzerland: A Retrospective Study of Transfer from Soil to the Human Body.

Natural radionuclides are ubiquitous in the environment. In addition, artificial radionuclides are present in the Swiss environment after the fallout of the nuclear bomb tests of the 1950s and 1960s, after the accident of the Chernobyl nuclear power plant, or after authorized discharges from the Swiss nuclear power plants and research centres. These radionuclides can create a radiological hazard to the environment and humans because of the increased risk of cancer due to the ionizing radiation they produce. Here we show that some of these radionuclides have made their way from the air or the soil to the human body, where they target mostly the skeleton. However, the activity levels of 90 Sr, 239 Pu and 240 Pu, 226 Ra and 210 Pb/ 210 Po found in the human body remain very low and do not represent a public health issue at the current body burden.

Origin and stability of uranium accumulation-layers in an Alpine histosol.

Uranium (U) accumulation in organic soils is a common phenomenon that can lead to high U concentration in montane wetlands. The stability of the immobilized U in natural wetlands following redox fluctuations and re-oxidation events, however, is not currently known. In this study, we investigated a saturated histosol that had accumulated up to 6000 ppm of U at 30 cm below ground level (bgl). Uranium in the waters feeding the wetland originates from the weathering of surrounding gneiss rocks, a process releasing trace amounts (<3 ppb) of soluble U into nearby streams. Redox oscillations in the first 20 cm bgl led to the accumulation of U, Ca, S in low permeability layers at 30 and 45 cm bgl. XRF measurements along the core showed that U strongly correlates with sulfur (S) and calcium (Ca), but not iron (Fe). We tested the stability of uranium in the histosol over a nine-month laboratory amendment of a large core of the histosol (∅ 30 cm; length 55 cm) with up to 500 ppm nitrate. Nitrate addition was followed by complete nitrate reduction and re-generation of oxidizing Eh conditions in the top 25 cm of the soil without U release to the soil pore waters above background levels (1-2 ppb). Our results demonstrate that, fast reduction of nitrate, sulfate, and Fe(III) occur in the soil without U release. The remarkable stability of sorbed U in the histosol may result from buffering by sulfide and Sn° and/or strong U(IV)-OM or U(VI)-OM enhanced by organic S moieties or bridging complexation by Ca. That U in the soil was immobile under nitrate addition for up to 9 months can inform remediation strategies based on the use of artificial wetlands to limit U mobility in contaminated sites.

Determination of 226Ra at low levels in environmental, urine, and human bone samples and 223Ra in bone biopsy using alpha-spectrometry and metrological traceability to 229Th/225Ra or 226Ra.

226Ra is a natural radioelement emitting α and γ radiations. It can be highly concentrated in TENORM materials from the petroleum or fertilizer industries. In Switzerland, 226Ra is currently a radioactive inheritance problem from the watch industry. Furthermore, 223Ra is a radium isotope used in nuclear medicine to treat bone metastasis. There exist several methods to measure radium using alpha or gamma spectrometry or using 222Rn emanation technique. The limitations of these methods are due to the required detection limits and the nature of the samples. When using alpha spectrometry to reach very low detection limits, critical technical hitches often arise because of the difficulties in separating radium from barium, in removing organics eluted from the separating chromatography column, and in plating radium. Moreover, overall chemical recovery of radium is often not reproducible, depending on the studies. Here we propose a method that separates radium from other alkaline-earth cations using cation exchange chromatography and selective complex formation by EDTA and DCTA. Radium is completely free of the 229Th tracer and its daughter products, particularly 225Ac. Organics from the column are removed in a further purification step so that radium can be plated with acceptable yields in a HCl/HNO3/ethanol solution. We successfully applied the method to soil, water, urine and human bone samples and further extended it to the determination of 223Ra in a bone biopsy, using 226Ra as an internal tracer.

A new two-strip TLC method for the quality control of technetium-99m mercaptoacetyl-triglycine (99mTc-MAG3).

BACKGROUND: 99mTc-mercaptoacetyl-triglycine (99mTc-MAG3) has been used for dynamic renal imaging since about 30 years. Free pertechnetate (99mTcO4), colloidal 99mTc ((99mTcO2)n), 99mTc-tartrate (precursor), precomplexes (99mTc-(MAG3)x) and lipophilic 99mTc-MAG2 are the main radiochemical impurities that may occur in the preparation. The total amount of these impurities has to be identified before release of the product for patient administration to guarantee patient safety and good image quality. The European Pharmacopoeia suggests a method based on high-pressure liquid chromatography analysis in combination with a paper chromatography. This analytical method is time consuming, expensive and requires specially trained technicians. As a consequence, it is not widely applied in nuclear medicine radiopharmacies. RESULTS: We developed a simple method for radiochemical purity testing of 99mTc-MAG3. The method is based on thin layer chromatography with two strips to be developed in parallel. Method validation was carried out in comparison to the official methods of the companies and to the European Pharmacopoeia method. It was tested on specificity, accuracy, robustness and precision. CONCLUSION: The proposed method is able to identify and quantify the sum of all impurities occurring in the preparation, respecting the acceptance criteria for the radiochemical purity defined by the official methods. Hydrophilic and lipophilic compounds are identified separately and results are obtained within less than 20 minutes. Our method is simple, cost effective, fast and is suitable for employing dose calibrators or radiometric scanners.

Impact of glacial/interglacial sea level change on the ocean nitrogen cycle.

The continental shelves are the most biologically dynamic regions of the ocean, and they are extensive worldwide, especially in the western North Pacific. Their area has varied dramatically over the glacial/interglacial cycles of the last million years, but the effects of this variation on ocean biological and chemical processes remain poorly understood. Conversion of nitrate to N2 by denitrification in sediments accounts for half or more of the removal of biologically available nitrogen ("fixed N") from the ocean. The emergence of continental shelves during ice ages and their flooding during interglacials have been hypothesized to drive changes in sedimentary denitrification. Denitrification leads to the occurrence of phosphorus-bearing, N-depleted surface waters, which encourages N2 fixation, the dominant N input to the ocean. An 860,000-y record of foraminifera shell-bound N isotopes from the South China Sea indicates that N2 fixation covaried with sea level. The N2 fixation changes are best explained as a response to changes in regional excess phosphorus supply due to sea level-driven variations in shallow sediment denitrification associated with the cyclic drowning and emergence of the continental shelves. This hypothesis is consistent with a glacial ocean that hosted globally lower rates of fixed N input and loss and a longer residence time for oceanic fixed N-a "sluggish" ocean N budget during ice ages. In addition, this work provides a clear sign of sea level-driven glacial/interglacial oscillations in biogeochemical fluxes at and near the ocean margins, with implications for coastal organisms and ecosystems.

(210)Po poisoning as possible cause of death: forensic investigations and toxicological analysis of the remains of Yasser Arafat.

The late president of the Palestinian Authority, Yasser Arafat, died in November 2004 in Percy Hospital, one month after having experienced a sudden onset of symptoms that included severe nausea, vomiting, diarrhoea and abdominal pain and which were followed by multiple organ failure. In spite of numerous investigations performed in France, the pathophysiological mechanisms at the origin of the symptoms could not be identified. In 2011, we found abnormal levels of polonium-210 ((210)Po) in some of Arafat's belongings that were worn during his final hospital stay and which were stained with biological fluids. This finding led to the exhumation of Arafat's remains in 2012. Significantly higher (up to 20 times) activities of (210)Po and lead-210 ((210)Pb) were found in the ribs, iliac crest and sternum specimens compared to reference samples from the literature (p-value <1%). In all specimens from the tomb, (210)Po activity was supported by a similar activity of (210)Pb. Biokinetic calculations demonstrated that a (210)Pb impurity, as identified in a commercial source of 3MBq of (210)Po, may be responsible for the activities measured in Arafat's belongings and remains 8 years after his death. The absence of myelosuppression and hair loss in Mr Arafat's case compared to Mr Litvinenko's, the only known case of malicious poisoning with (210)Po, could be explained by differences in the time delivery-scheme of intake. In conclusion, statistical Bayesian analysis combining all the evidence gathered in our forensic expert report moderately supports the proposition that Mr Arafat was poisoned by (210)Po.

Iron fertilization of the Subantarctic ocean during the last ice age.

John H. Martin, who discovered widespread iron limitation of ocean productivity, proposed that dust-borne iron fertilization of Southern Ocean phytoplankton caused the ice age reduction in atmospheric carbon dioxide (CO2). In a sediment core from the Subantarctic Atlantic, we measured foraminifera-bound nitrogen isotopes to reconstruct ice age nitrate consumption, burial fluxes of iron, and proxies for productivity. Peak glacial times and millennial cold events are characterized by increases in dust flux, productivity, and the degree of nitrate consumption; this combination is uniquely consistent with Subantarctic iron fertilization. The associated strengthening of the Southern Ocean's biological pump can explain the lowering of CO2 at the transition from mid-climate states to full ice age conditions as well as the millennial-scale CO2 oscillations.

Changes in North Atlantic nitrogen fixation controlled by ocean circulation.

In the ocean, the chemical forms of nitrogen that are readily available for biological use (known collectively as 'fixed' nitrogen) fuel the global phytoplankton productivity that exports carbon to the deep ocean. Accordingly, variation in the oceanic fixed nitrogen reservoir has been proposed as a cause of glacial-interglacial changes in atmospheric carbon dioxide concentration. Marine nitrogen fixation, which produces most of the ocean's fixed nitrogen, is thought to be affected by multiple factors, including ocean temperature and the availability of iron and phosphorus. Here we reconstruct changes in North Atlantic nitrogen fixation over the past 160,000 years from the shell-bound nitrogen isotope ratio ((15)N/(14)N) of planktonic foraminifera in Caribbean Sea sediments. The observed changes cannot be explained by reconstructed changes in temperature, the supply of (iron-bearing) dust or water column denitrification. We identify a strong, roughly 23,000-year cycle in nitrogen fixation and suggest that it is a response to orbitally driven changes in equatorial Atlantic upwelling, which imports 'excess' phosphorus (phosphorus in stoichiometric excess of fixed nitrogen) into the tropical North Atlantic surface. In addition, we find that nitrogen fixation was reduced during glacial stages 6 and 4, when North Atlantic Deep Water had shoaled to become glacial North Atlantic intermediate water, which isolated the Atlantic thermocline from excess phosphorus-rich mid-depth waters that today enter from the Southern Ocean. Although modern studies have yielded diverse views of the controls on nitrogen fixation, our palaeobiogeochemical data suggest that excess phosphorus is the master variable in the North Atlantic Ocean and indicate that the variations in its supply over the most recent glacial cycle were dominated by the response of regional ocean circulation to the orbital cycles.