Whole body potassium as a biomarker for potassium uptake using a mouse model.

Potassium is known for its effect on modifiable chronic diseases like hypertension, cardiac disease, diabetes (type-2), and bone health. In this study, a new method, neutron generator based neutron activation analysis (NAA), was utilized to measure potassium (K) in mouse carcasses. A DD110 neutron generator based NAA assembly was used for irradiation.Thirty-two postmortem mice (n= 16 males and 16 females, average weight [Formula: see text] and [Formula: see text] g) were employed for this study. Soft-tissue equivalent mouse phantoms were prepared for the calibration. All mice were irradiated for 10 minutes, and the gamma spectrum with 42K was collected using a high efficiency, high purity germanium (HPGe) detector. A lead shielding assembly was designed and developed around the HPGe detector to obtain an improved detection limit. Each mouse sample was irradiated and measured twice to reduce uncertainty. The average potassium concentration was found to be significantly higher in males [Formula: see text] compared to females [Formula: see text]. We also observed a significant correlation between potassium concentration and the weight of the mice. The detection limit for potassium quantification with the NAA system was 46 ppm. The radiation dose to the mouse was approximately 56 [Formula: see text] mSv for 10-min irradiation. In conclusion, this method is suitable for estimating individual potassium concentration in small animals. The direct evaluation of total body potassium in small animals provides a new way to estimate potassium uptake in animal models. This method can be adapted later to quantify potassium in the human hand and small animals in vivo. When used in vivo, it is also expected to be a valuable tool for longitudinal assessment, kinetics, and health outcomes.

An overview on radiometric assessment and excess lifetime cancer risk of soil in Pakistan by using High Purity Germanium (HPGe) detector.

OBJECTIVES: The aim of this study is to compare the natural radioactivity and excess life time cancer risk (ELCR) factor of soil in different regions of Pakistan during last decade. Soil contains various elements and compounds including naturally occurring radioactive elements (238U, 232Th, 40K and 137Cs). Human being, animals and plants are in health risk by contaminations of natural radioactivity in soil and environmental radiometric pollution. Transferring of large amount of the natural radioactive elements in human body by nutrients may cause carcinogenic effects in human body. Pakistani soil has six types as Indus Basin Soil, Bongar Soil, Khaddar Soil, Indus delta soil, Mountainous soil and Sandy Desert Soil. In some northern region of Pakistan, naturally occurring radioactive rocks like uranuium-238 and iridium concentrations present in Gharwandi, Aram, Kingri S, Vitakri Fort Munro, Dera Bugti, Kohlu and Sibbi districts. METHODS: In this reviewed data, gamma rays spectroscopy used to determine the concentrations of 238U, 232Th and 40K with the help of High Purity Germanium (HPGe) detectors. Only the data of HPGe detector collected because of comparisons of different regions of Pakistan. RESULTS AND CONCLUSIONS: Mostly, different gamma rays energy peaks of relevant daughter radionuclides of radioactive element were used such as the energy peak lines of daughter radionuclides 214Pb (295.21 and 352 KeV) and 214Bi (609 and 1,120 KeV) used for calculating the 226Ra concentration in soil. In the recent study, it is concluded that average values of concentrations of natural radioactivity in soil in central and north regions of Pakistan are higher than permissible limit but found permissible range in south region of Pakistan. Mean values of ELCR factor were found higher, equal and lower in central, north and south regions than permissible limit, respectively. Generally, no serious health hazard due to natural radioactivity in soil were found.

Evaluation of 72Se/72As generator and production of 72Se for supplying 72As as a potential PET imaging radionuclide.

Positron-emitting 72As is the PET imaging counterpart for beta-emitting 77As. Its parent, no carrier added (n.c.a.) 72Se, was produced for a 72Se/72As generator by irradiating an enriched 7°Ge metal-graphite target via the 70Ge(α, 2 n)72Se reaction. Target dissolution used a fast, environmentally friendly method with 93% radioactivity recovery. Chromatographic parameters of the 72Se/72As generator were evaluated, the eluted n.c.a. 72As was characterized with a phantom imaging study, and the previously reported trithiol and aryl-dithiol ligand systems were radiolabeled with the separated n.c.a. 72As in high yield.

Chromatographic separation of germanium and arsenic for the production of high purity (77)As.

A simple column chromatographic method was developed to isolate (77)As (94±6% (EtOH/HCl); 74±11 (MeOH)) from germanium for potential use in radioimmunotherapy. The separation of arsenic from germanium was based on their relative affinities for different chromatographic materials in aqueous and organic environments. Using an organic or mixed mobile phase, germanium was selectively retained on a silica gel column as germanate, while arsenic was eluted from the column as arsenate. Subsequently, enriched (76)Ge (98±2) was recovered for reuse by elution with aqueous solution (neutral to basic). Greater than 98% radiolabeling yield of a (77)As-trithiol was observed from methanol separated [(77)As]arsenate [17].

[Manufacture and Utilization of a Low-level Radioactive 68Ge/68Ga Generator in a Radiochemistry Laboratory Course].

The low-level radioactivity of a (68)Ge/(68)Ga generator is a suitable tool for measuring radioactive growth and decay after (68)Ga milking due to their desirable nuclear decay properties, such as the EC decay of (68)Ge with no γ-ray emission andthe ß(+) decay of (68)Ga with a weak γ-ray emission. To experience andund erstandrad ioactive equilibrium during a university laboratory course, we surveyedandtestedthe production of a small amount of (68)Ge and set up educational programs to manufacture a (68)Ge/(68)Ga generator for measuring the growth andd ecay of (68)Ga. The irradiation of natGa with 25 µA of a 30 MeV proton beam from a cyclotron for 4 h yields ca. 111 MBq of (68)Ge, which was sufficient to supply to several universities. For use as the adsorbent of the generator column, particles of hydrated tin (VI) oxide were prepared from precipitated tin hydroxide gel. Repeated elution of (68)Ga from the handmade (68)Ge/(68)Ga generator gave constant amounts of (68)Ga with acceptable breakthrough of (68)Ge. The feedback from the student's experience with the (68)Ge/(68)Ga generator was evaluatedby annual questionnaire surveys, which were given to all students taking the course every year from 2012 to 2014. It has been made clear that more than half of the students were interested in the (68)Ge/(68)Ga generator program, andthis interest increasedfrom 54.9%in 2012 to 78.6%in 2014. A low-level radioactive (68)Ge/(68)Ga generator is thus expectedto be a suitable experimental tool for demonstrating the phenomenon of radioactivity to students in an intriguing way.

Chemical Functionalization of Germanium with Dextran Brushes for Immobilization of Proteins Revealed by Attenuated Total Reflection Fourier Transform Infrared Difference Spectroscopy.

Protein immobilization studied by attenuated total reflection Fourier transform infrared (ATR-FT-IR) difference spectroscopy is an emerging field enabling the study of proteins at atomic detail. Gold or glass surfaces are frequently used for protein immobilization. Here, we present an alternative method for protein immobilization on germanium. Because of its high refractive index and broad spectral window germanium is the best material for ATR-FT-IR spectroscopy of thin layers. So far, this technique was mainly used for protein monolayers, which lead to a limited signal-to-noise ratio. Further, undesired protein-protein interactions can occur in a dense layer. Here, the germanium surface was functionalized with thiols and stepwise a dextran brush was generated. Each step was monitored by ATR-FT-IR spectroscopy. We compared a 70 kDa dextran with a 500 kDa dextran regarding the binding properties. All surfaces were characterized by atomic force microscopy, revealing thicknesses between 40 and 110 nm. To analyze the capability of our system we utilized N-Ras on mono-NTA (nitrilotriacetic acid) functionalized dextran, and the amount of immobilized Ras corresponded to several monolayers. The protein stability and loading capacity was further improved by means of tris-NTA for immobilization. Small-molecule-induced changes were revealed with an over 3 times higher signal-to-noise ratio compared to monolayers. This improvement may allow the observation of very small and so far hidden changes in proteins upon stimulus. Furthermore, we immobilized green fluorescent protein (GFP) and mCherry simultaneously enabling an analysis of the surface by fluorescence microscopy. The absence of a Förster resonance energy transfer (FRET) signal demonstrated a large protein-protein distance, indicating an even distribution of the protein within the dextran.

Quantitative online isolation of 68Ge from 68Ge/68Ga generator eluates for purification and immediate quality control of breakthrough.

The breakthrough of 68Ge from a 68Ge/68Ga-generator is one of the most sensitive parameters in the context of the clinical application of 68Ga-radiopharmaceuticals. The difficulty in its determination lies in the "spectroscopic invisibility" of 68Ge within an excess of 68Ga. The introduced method for determining the 68Ge content of the 68Ge/68Ga-generator eluate involves the quantitative separation of 68Ga from 68Ge, using a cation-exchanger. The eluate contains 68Ga free of 68Ge, which can be determined immediately, i.e. prior to the application of the 68Ga-radiopharmaceutical.

Maturation of a key resource - the germanium-68/gallium-68 generator: development and new insights.

(68)Ge/(68)Ga radionuclide generators have been investigated for almost fifty years, since the cyclotron-independent availability of positron emitting (68)Ga via the (68)Ge/(68)Ga system had always attracted researches working in basic nuclear chemistry as well as radiopharmaceutical chemistry. However, it took decades and generations of research (and researchers) to finally reach a level of (68)Ge/(68)Ga radionuclide generator designs adequate to the modern requirements of radiometal labelling chemistry. Nevertheless, most of the existing commercial generator systems address aspects of (68)Ge breakthrough and safe synthesis of (68)Ga radiopharmaceuticals by adopting eluate post-processing technologies. Among the strategies to purify (68)Ga eluates, the cation exchange based version is relevant in terms of purification efficiency. In addition, it offers more options towards further developments of (68)Ga radiopharmaceuticals. Today, one may expect that the (68)Ge/(68)Ga radionuclide generator systems could contribute to the clinical impact of nuclear medicine diagnoses for PET similar to the established (99)Mo/(99m)Tc generator system for SPECT. The exciting perspective for the (68)Ge/(68)Ga radionuclide generator system, in turn, asks for systematic chemical, radiochemical, technological and radiopharmaceutical efforts, to guarantee reliable, highly-efficient and medically approved (68)Ge/(68)Ga generator systems.

Feasibility and availability of 68Ga-labelled peptides.

(68)Ga has attracted tremendous interest as a radionuclide for PET based on its suitable half-life of 68 min, high positron emission yield and ready availability from (68)Ge/(68)Ga generators, making it independent of cyclotron production. (68)Ga-labelled DOTA-conjugated somatostatin analogues, including DOTA-TOC, DOTA-TATE and DOTA-NOC, have driven the development of technologies to provide such radiopharmaceuticals for clinical applications mainly in the diagnosis of somatostatin receptor-expressing tumours. We summarize the issues determining the feasibility and availability of (68)Ga-labelled peptides, including generator technology, (68)Ga generator eluate postprocessing methods, radiolabelling, automation and peptide developments, and also quality assurance and regulatory aspects. (68)Ge/(68)Ga generators based on SnO(2), TiO(2) or organic matrices are today routinely supplied to nuclear medicine departments, and a variety of automated systems for postprocessing and radiolabelling have been developed. New developments include improved chelators for (68)Ga that could open new ways to utilize this technology. Challenges and limitations in the on-site preparation and use of (68)Ga-labelled peptides outside the marketing authorization track are also discussed.

Development of a nano-zirconia based 68Ge/68Ga generator for biomedical applications.

INTRODUCTION: Most of the commercially available (68)Ge/(68)Ga generator systems are not optimally designed for direct applications in a clinical context. We have developed a nano-zirconia based (68)Ge/(68)Ga generator system for accessing (68)Ga amenable for the preparation of radiopharmaceuticals. METHODS: Nano-zirconia was synthesized by the in situ reaction of zirconyl chloride with ammonium hydroxide in alkaline medium. The physical characteristics of the material were studied by various analytical techniques. A 740 MBq (20 mCi) (68)Ge/(68)Ga generator was developed using this sorbent and its performance was evaluated for a period of 1 year. The suitability of (68)Ga for labeling biomolecules was ascertained by labeling DOTA-TATE with (68)Ga. RESULTS: The material synthesized was nanocrystalline with average particle size of ~7 nm, pore-size of ~4 Å and a high surface area of 340±10 m(2) g(-1). (68)Ga could be regularly eluted from this generator in 0.01N HCl medium with an overall radiochemical yield >80% and with high radionuclidic (<10(-5)% of (68)Ge impurity) and chemical purity (<0.1 ppm of Zr, Fe and Mn ions). The compatibility of the product for preparation of (68)Ga-labeled DOTA-TATE under the optimized reaction conditions was found to be satisfactory in terms of high labeling yields (>99%). The generator gave a consistent performance with respect to the elution yield and purity of (68)Ga over a period of 1 year. CONCLUSIONS: The feasibility of preparing an efficient (68)Ge/(68)Ga generator which can directly be used for biomedical applications has been demonstrated.

Germanium recovery from gasification fly ash: evaluation of end-products obtained by precipitation methods.

In this study the purity of the germanium end-products obtained by two different precipitation methods carried out on germanium-bearing solutions was evaluated as a last step of a hydrometallurgy process for the recovery of this valuable element from the Puertollano Integrated Gasification Combined Cycle (IGCC) fly ash. Since H(2)S is produced as a by-product in the gas cleaning system of the Puertollano IGCC plant, precipitation of germanium as GeS(2) was tested by sulfiding the Ge-bearing solutions. The technological and hazardous issues that surround H(2)S handling conducted to investigate a novel precipitation procedure: precipitation as an organic complex by adding 1,2-dihydroxy benzene pyrocatechol (CAT) and cetyltrimethylammonium bromide (CTAB) to the Ge-bearing solutions. Relatively high purity Ge end-products (90 and 93% hexagonal-GeO(2) purity, respectively) were obtained by precipitating Ge from enriched solutions, as GeS(2) sulfiding the solutions with H(2)S, or as organic complex with CAT/CTAB mixtures and subsequent roasting of the precipitates. Both methods showed high efficiency (>99%) to precipitate selectively Ge using a single precipitation stage from germanium-bearing solutions.

Concentration of 68Ga via solvent extraction.

The metallic cation, (68)Ga (III) is suitable for complexation with chelators either naked or conjugated with biological macromolecules, however, such labeling procedure requires high chemical purity and concentrated solutions of (68)Ga (III), which cannot be sufficiently fulfilled by the presently available (68)Ge/(68)Ga generator eluate. A method to increase the concentration and purity of (68)Ga obtained from a commercial (68)Ge/(68)Ga generator has been developed. The (68)Ga eluate (1M HCl) is extracted in methyl ethyl ketone, which is evaporated and taken in a small volume of buffer.

A versatile technique for radiochemical separation of medically useful no-carrier-added (nca) radioarsenic from irradiated germanium oxide targets.

A method for the separation of no-carrier-added (nca) arsenic radionuclides from bulk amounts of irradiated germanium oxide (GeO2) target was developed in view of their potentialities in different biological and nuclear medicine applications. The beta- emitting 77As radionuclide, produced by the decay of 77Ge through the natGe(n,gamma)77Ge nuclear reaction, was used for standardization of the radiochemical separation procedure. The radiochemical separation was performed by precipitation followed by solvent extraction. About 99% post-irradiation recovery of the GeO2 target material, in a form suitable for reuse in future irradiation, was achieved. The developed method was suitable for the production of nca arsenic radionuclides either as trivalent or pentavalent arsenic in various vehicles which provided flexibility of formulations of different kinds of compound. The overall radiochemical yield for the complete separation of 77As was 90%. The separated nca 77As was of high radionuclidic purity and did not contain detectable amounts of the target material. This method can be adopted for the radiochemical separation of other different arsenic radionuclides produced from GeO2 through cyclotron as well as reactor irradiation.

High-speed recovery of germanium in a convection-aided mode using functional porous hollow-fiber membranes.

A porous hollow-fiber membrane capable of recovery of germanium from a liquid stream was prepared by radiation-induced graft polymerization of an epoxy-group-containing vinyl monomer, glycidyl methacrylate, and subsequent functionalization with 2,2'-iminodiethanol, di-2-propanolamine, N-methylglucamine, and 3-amino-1,2-propanediol. The functional group density was as high as 1.4 mol per kg of the resultant hollow fiber. The polymer chains containing functional groups surrounding the pores enabled a high-speed recovery of germanium during permeation of a germanium oxide (GeO2) solution through the pores of the hollow fiber. Because of a negligible diffusional mass-transfer resistance, germanium concentration changes with the effluent volume, i.e., breakthrough curves, overlapped irrespective of the residence time of the solution, which ranged from 0.37 to 3.7 s across the hollow fiber. After repeated use of adsorption and elution, the adsorption capacity did not deteriorate.

Potential column chromatography generators for ionic Ga-68. I. Inorganic substrates.

Chemical separations for Ga-68 from Ge-68 using adsorption chromatography on inorganic materials are described. The adsorbents used were TiO2, ZrO2, and SiO2. Distribution coefficients for Ge and Ga on these absorbents were determined as a function of reagent concentration and duration of equilibration. The distribution coefficient (w/w) for Ge on SiO2 reached 250 in 6 N HNO3, whereas Ga was no significantly adsorbed. Therefore, Ga-68 can be collected with a mall volume of 6 N HNO3 eluent. By contrast, large volumes of 1 N HNO3 were necessary to collect Ga-68 from ZrO2, since the KD of Ga under these circumstances was about 50. The Ga-68 eluted from TiO2 was chemically contaminated with titanates and would require additional chemical manipulation in order to make it injectable. All the adsorbents could lead to chromatographic systems that would allow acceptable chemical separations. However, the specific requirements for a radionuclide generator, usable in a hospital environment, make the SiO2-based system the most attractive.