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.

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.

The effects of trace metal impurities on Ga-68-radiolabelling with a tris(3-hydroxy-1,6-dimethylpyridin-4-one) (THP) chelator.

GMP-grade 68Ge/68Ga generators provide access to positron-emitting 68Ga, enabling preparation of Positron Emission Tomography (PET) tracers and PET imaging at sites that do not have access to cyclotron-produced radionuclides. Radiotracers based on tris(3-hydroxy-1,6-dimethylpyridin-4-one) (THP) chelators enable simple one-step preparations of 68Ga PET radiopharmaceuticals from pre-fabricated kits without pre-processing of generator eluate or post-purification. However, trace metal impurities eluted along with 68Ga could compete for THP and reduce radiochemical yields (RCY). We have quantified trace metal impurities in 68Ga eluate from an Eckert & Ziegler (E&Z) generator using ICP-MS. The metals Al, Fe, natGa, Pb, Ti and natZn were present in generator eluate in significantly higher concentrations than in the starting eluent solution. Concentrations of Fe and natGa in eluate were in the range of 0.01-0.1 µM, Al, Zn and Pb in the range of 0.1-1 µM, and Ti in the range of 0.9-1.5 µM. To assess the ability of THP to chelate 68Ga in the presence of such metal ions, radiolabelling reactions were undertaken in which selected metal ions were added to make them equimolar with THP, or higher. Al3+, Fe3+, natGa3+ and Ti4+ reduced RCY at concentrations equimolar with THP and higher, but at lower concentrations they did not affect RCY. Pb2+, Zn2+, Ni2+ and Cr3+ had no effect on RCY (even under conditions in which each metal ion was present in 100-fold molar excess over THP). The multi-sample ICP-MS analysis reported here is (to date) the most comprehensive and robust quantification of metal impurities in the widely used E&Z 68Ga generator. 68Ga from an E&Z generator enables near-quantitative radiolabelling of THP at chelator concentrations as low as 5 µM (lower than other common gallium chelators) without pre-processing. The combination of Al3+, Fe3+, natGa3+ and Ti4+ in unprocessed 68Ga eluate is likely to decrease RCY of 68Ga radiolabelling if a lower amount of THP chelator is used, and future kit design should take this into account. To increase specific activities by using even lower THP concentrations, purification of 68Ga from trace metal ions will likely be required.

Hydroxypyridinone Chelators: From Iron Scavenging to Radiopharmaceuticals for PET Imaging with Gallium-68.

Derivatives of 3,4-hydroxypyridinones have been extensively studied for in vivo Fe3+ sequestration. Deferiprone, a 1,2-dimethyl-3,4-hydroxypyridinone, is now routinely used for clinical treatment of iron overload disease. Hexadentate tris(3,4-hydroxypyridinone) ligands (THP) complex Fe3+ at very low iron concentrations, and their high affinities for oxophilic trivalent metal ions have led to their development for new applications as bifunctional chelators for the positron emitting radiometal, 68Ga3+, which is clinically used for molecular imaging in positron emission tomography (PET). THP-peptide bioconjugates rapidly and quantitatively complex 68Ga3+ at ambient temperature, neutral pH and micromolar concentrations of ligand, making them amenable to kit-based radiosynthesis of 68Ga PET radiopharmaceuticals. 68Ga-labelled THP-peptides accumulate at target tissue in vivo, and are excreted largely via a renal pathway, providing high quality PET images.

Probing the Kinetic Parameters of Plutonium-Naturally Occurring Organic Matter Interactions in Freshwaters Using the Diffusive Gradients in Thin Films Technique.

The interaction of trace metals with naturally occurring organic matter (NOM) is a key process of the speciation of trace elements in aquatic environments. The rate of dissociation of metal-NOM complexes will impact the amount of free metal available for biouptake. Assessing the bioavailability of plutonium (Pu) helps to predict its toxic effects on aquatic biota. However, the rate of dissociation of Pu-NOM complexes in natural freshwaters is currently unknown. Here, we used the technique of diffusive gradients in thin films (DGT) with several diffusive layer thicknesses to provide new insights into the dissociation kinetics of Pu-NOM complexes. Results show that Pu complexes with NOM (mainly fulvic acid) are somewhat labile (0.2 ≤ ξ ≤ 0.4), with kd = 7.5 × 10(-3) s(-1). DGT measurements of environmental Pu in organic-rich natural water confirm these findings. In addition, we determined the effective diffusion coefficients of Pu(V) in polyacrylamide (PAM) gel in the presence of humic acid using a diffusion cell (D = 1.70 ± 0.25 × 10(-6) cm(2) s(-1)). These results show that Pu(V) is a more mobile species than Pu(IV).

Speciation and Bioavailability Measurements of Environmental Plutonium Using Diffusion in Thin Films.

The biological uptake of plutonium (Pu) in aquatic ecosystems is of particular concern since it is an alpha-particle emitter with long half-life which can potentially contribute to the exposure of biota and humans. The diffusive gradients in thin films technique is introduced here for in-situ measurements of Pu bioavailability and speciation. A diffusion cell constructed for laboratory experiments with Pu and the newly developed protocol make it possible to simulate the environmental behavior of Pu in model solutions of various chemical compositions. Adjustment of the oxidation states to Pu(IV) and Pu(V) described in this protocol is essential in order to investigate the complex redox chemistry of plutonium in the environment. The calibration of this technique and the results obtained in the laboratory experiments enable to develop a specific DGT device for in-situ Pu measurements in freshwaters. Accelerator-based mass-spectrometry measurements of Pu accumulated by DGTs in a karst spring allowed determining the bioavailability of Pu in a mineral freshwater environment. Application of this protocol for Pu measurements using DGT devices has a large potential to improve our understanding of the speciation and the biological transfer of Pu in aquatic ecosystems.

A DGT technique for plutonium bioavailability measurements.

The toxicity of heavy metals in natural waters is strongly dependent on the local chemical environment. Assessing the bioavailability of radionuclides predicts the toxic effects to aquatic biota. The technique of diffusive gradients in thin films (DGT) is largely exploited for bioavailability measurements of trace metals in waters. However, it has not been applied for plutonium speciation measurements yet. This study investigates the use of DGT technique for plutonium bioavailability measurements in chemically different environments. We used a diffusion cell to determine the diffusion coefficients (D) of plutonium in polyacrylamide (PAM) gel and found D in the range of 2.06-2.29 × 10(-6) cm(2) s(-1). It ranged between 1.10 and 2.03 × 10(-6) cm(2) s(-1) in the presence of fulvic acid and in natural waters with low DOM. In the presence of 20 ppm of humic acid of an organic-rich soil, plutonium diffusion was hindered by a factor of 5, with a diffusion coefficient of 0.50 × 10(-6) cm(2) s(-1). We also tested commercially available DGT devices with Chelex resin for plutonium bioavailability measurements in laboratory conditions and the diffusion coefficients agreed with those from the diffusion cell experiments. These findings show that the DGT methodology can be used to investigate the bioaccumulation of the labile plutonium fraction in aquatic biota.