Extractive scintillating resin for 99Tc quantification in aqueous solutions

A method utilizing extractive scintillating resin for ⁹⁹Tcmonitoring in aqueous solutions is presented. These extractive scintillatorscombine analyte selective uptake and scintillating properties to produce dualfunctionality analytical resins. These resins were produced by (1) co-locatedextraction chromatographic resin and plastic scintillating beads, (2) immobilizingfluors in macroporous polystyrene supports to which chains of monomethylatedpolyethylene glycol have been grafted and (3) co-immobilizing organic scintillatingfluors and a quaternary ammonium extractant (Aliquat-336) within macroporousacrylic and polystyrene supports. The first and third resins selectively extractpertechnetate ions from dilute acid whereas the second resin selectively extractspertechnetate ions from high ionic strength solutions. These resins were utilizedin ~0.20 ml pore volume columns while ⁹⁹Tc was continually monitoredwith commercially available scintillation detection systems. Manual and automatedmicrofluidics were used to deliver sample and reagent solution for loadingand elution of the ⁹⁹Tc. The detection efficiencies were determinedto be 45 and 70% for acrylic and polystyrene based resins, respectively, andindependent of extractant. Minimum detectable ⁹⁹Tc concentrationusing the Aliquat-336/acrylic-based resin was 6.2 Bq . l –1 for a 50-mlsample and 30-minute count time. The new methodology was applied towards analysisof contaminated groundwater samples and nuclear waste simulants.     

Determination of technetium-99 in soils and radioactive wastes using ICP-MS

Three methods have been used for the determination of ⁹⁹Tc in soils and solid radioactive wastes using ^99mTc as a yield monitor. In the method one and three the samples were leached in low concentrated nitric and sulphuric acid. Many contaminants were then co-precipitated with Fe(OH)₃ in alkali media and Tc in the supernatant was separated using anion-exchange extraction chromatography. There were made also some studies how to improve the chemical recovery of ^99mTc in the process of chromatography. In the method two the sample was ashed and then leached in 8 mol dm⁻³ HNO₃ and after iron precipitation, technetium was separated on chromatographic column. The chemical recovery of ^99mTc was optimized in the process of chromatography and leaching. Typical recoveries of technetium determined with ^99mTc tracer for all these methods were in the range 39 %–87 %. The ⁹⁹Tc activity was measured using proportional low-background beta detector after one week of staying to allow decay of ^99mTc activity. ⁹⁹Tc was also determined by the non-radiometric method using inductively coupled plasma mass spectrometer.     

Chemical and radiochemical evaluation of the purity of99mTc extracted by MEK

Solvent extraction separation of^99mTc from⁹⁹Mo using methyl ethyl ketone(MEK) has been found to be an effective method of obtaining^99mTc of medicinal purity from low specific activity⁹⁹Mo. The authors have investigated the effect of alkali and molybdenum concentration on the extraction of⁹⁹Mo and^99mTc into methyl ethyl ketone. The possibility of methyl ethyl ketone forming enol and condensation products and its effect on the final extraction efficiency and purity of^99mTc has been studied. Sodium molybdate has been found to have a good salting out effect on^99mTc pertechnetate and hence^99mTc extraction can be better accomplished from low specific activity⁹⁹Mo solutions. The ketone seems to form traces of condensation products in the extraction procedure. These have been found to be coextracted with^99mTc into MEK but did not affect the extractability of^99mTc. It was observed that neutral alumina column removes these condensation products from MEK containing^99mTc. Alternately these could be filtered off by acidification of the final aqueous^99mTc solution. The studies indicate that under optimum experimental conditions methyl ethyl ketone separates^99mTc from⁹⁹Mo with high efficiency and yields^99mTc of high purity suitable for use in nuclear medicine in the form of various labelled compounds.     

Technetium-99m extraction and transport across tri-n-octylamine-xylene based supported liquid membranes

The nuclear properties of^99mTc radionuclide are ideal for organ imaging. Study of the technetium transport across supported liquid membranes has been performed to get data for its separation from other elements. Tri-n-octylamine diluted in xylene was used to constitute the liquid membranes, supported in polypropylene microporous films. Stripping on the product solution side was performed with dilute NaOH solutions. The effect of sulphuric acid, nitric acid and hydrochloric acid in the feed on transport of^99mTc as TcO ₄ ^– ions has been studied. The permeability of the given ions determined from kinetic activity data has been found to be in the order of PH₂SO₄>PHCl>PHNO₃. The flux values have been calculated based on this permeability data. The increase in carrier concentration has shown an increase in flux and permeability values to a given optimum concentration. The increase in temperature has been found to reduce the transport of Tc ions. The optimum conditions for transport of^99mTc for the given acid concentration have been determined. Mechanism of Tc ion transport has also been provided based on chemical reactions involved at the membrane interfaces and uptake of Tc ions by the membrane. MoO ₄ ^2– ions do not permeate through membrane under optimum conditions of transport for TcO ₄ ^2– ions from H₂SO₄ solution.     

Views on quality tests of radiopharmaceuticals

The quality tests of radionuclides produced from generators (⁹⁹Mo→^99mTc,¹¹³Sn→^113mIn) have been reviewed. The quality controls of radiopharmaceuticals derived from these radionuclides and prepared with the help of ready-for-use reagents assembled in kits have been presented. The possibility of new tests regarding sterility (by means of a radiometric method) and detection of endotoxin (based on gelification of limulus amoebocyte lysate) have been suggested.     

Determination of technetium-99 in environmental samples: A review

Due to the lack of a stable technetium isotope, and the high mobility and long half-life, ⁹⁹Tc is considered to be one of the most important radionuclides in safety assessment of environmental radioactivity as well as nuclear waste management. ⁹⁹Tc is also an important tracer for oceanographic research due to the high technetium solubility in seawater as TcO₄⁻. A number of analytical methods, using chemical separation combined with radiometric and mass spectrometric measurement techniques, have been developed over the past decades for determination of ⁹⁹Tc in different environmental samples. This article summarizes and compares recently reported chemical separation procedures and measurement methods for determination of ⁹⁹Tc. Due to the extremely low concentration of ⁹⁹Tc in environmental samples, the sample preparation, pre-concentration, chemical separation and purification for removal of the interferences for detection of ⁹⁹Tc are the most important issues governing the accurate determination of ⁹⁹Tc. These aspects are discussed in detail in this article. Meanwhile, the different measurement techniques for ⁹⁹Tc are also compared with respect to advantages and drawbacks. Novel automated analytical methods for rapid determination of ⁹⁹Tc using solid extraction or ion exchange chromatography for separation of ⁹⁹Tc, employing flow injection or sequential injection approaches are also discussed.     

Rapid and sensitive determination of pertechnetate in99Mo/99mTc generator eluates by reversed-phase high-performance liquid chromatography

Reversed-phase high-performance liquid chromatography with u.v. detection was applied for rapid and sensitive determination of pertechnetate in⁹⁹Mo/^99mTc generator eluates, using a mixture solvent of acetonitrile and 0.04M aqueous acetate buffer (1/1) containing a few volume percentage of 0.5 M tetra-n-butylammonium hydroxide as the mobile phase. Employing a -bondapak C₁₃ column, the TcO ₄ ^– species was separated, monitored with absorbance at 254 nm, and observed at the retention time of 3.5 min. The detection limit was found to be 5.2·10^–10 g of Tc for each injection. Total Tc contents in the^99mTc eluates from clinically-used⁹⁹Mo/^99mTc generator were analyzed by this technique. The^99mTc (⁹⁹Tc) species was separated from the contaminant⁹⁹Mo. This method was found to be useful for the purification of^99mTc (⁹⁹Tc) as well as the determination of total Tc content.     

Quantification of99Tc by liquid scintillation counting: An evaluation of chemical quenching by liquid chromatographic eluents

The feasibility of utilizing liquid scintillation counting as a detection method for the liquid chromatographic analysis of⁹⁹Tc is evaluated. The chemical quenching of constituents commonly found in liquid chromatographic mobile phases is investigated, and quench corrections are presented. Quantification of⁹⁹Tc is achieved over a concentration range of 10^–3 to 10^–8M on quiescent KTCO₄ solutions, with sample volumes of 0.3 ml, yielding a counting efficiency from 51 to 59% for a narrow 150 channel window. The potential for the double isotope labelling of technetium complexes and the implications of the liquid scintillation counting of⁹⁹Tc in flowing eluents are discussed.     

Comparative radiochemical and kinetic study of tumorotropic and renal99mTc-DMSA

A procedure for obtaining a stable^99mTc(V)-DMSA kit and methods for its radiochemical and biological control are described. The effect of pH on radiopharmaceutical stability of the complex was studied. The kinetic parameters of^99mTc(V)-DMSA were determined on rats and compared to the corresponding values for renal^99mTC-DMSA. Clinical tests showed that^99mTc(V)-DMSA is suitable agent for detecting the primary medullar carcinoma of thyroid, as well as for detection of thyroid metastasis.     

Determination of technetium-99 in aqueous samples by isotope dilution inductively coupled plasma-mass spectrometry

An isotope dilution/inductively coupled plasma mass spectrometric method (ID/ICP-MS) for measuring the concentration of technetium-99 in aqueous samples was developed at the Savannah River Technology Center (SRTC). The procedure is faster than radiometric tecniques, is less subject to interferences, and has equal or better detection limits. It is currently being used to measure the concentration of⁹⁹Tc in samples of Savannah River water collected in the vicinity of the Savannah River Site. In this method one liter samples of water are spiked with⁹⁷Tc. After equilibration, the technetium is extracted from the sample with a chromatographic resin. Interfering elements, molybdenum and ruthenium, are either not retained by the resin or are washed off with, dilute nitric acid. The technetium is then eluted with more concentrated nitric acid, and the⁹⁹Tc/⁹⁷Tc ratio in the eluant is measured with an ICP-MS. The⁹⁹Tc concentration in the original sample is calculated from the⁹⁹Tc/⁹⁷Tc ratio. The chemical recovery of the extraction procedure is greater than 90%. The detection limit of the instrument, taken as three times the background counts atm/z=99, is 0.6 part per trillion (ppt). The detection limit of the procedure, taken as three times the standard deviation of several reagent blank analyses, is 0.33 pCi/l.     

Development of field portable sampling and analysis systems

A portable, field rugged, sampling and analysis system has been developed for the rapid screening of aqueous samples during scoping and remediation studies. Using field portable equipment, water is pumped through ion selective solid phase extraction (SPE) disks, at a flow rate of 150-250 ml/min, and counted for the radionuclide of interest in the field using portable detectors. SPE disks are currently available to selectively concentrate ⁹⁹Tc, ⁹⁰Sr, radiocesium (¹³⁴Cs and ¹³⁷Cs) and radium isotopes. In the field the radiocesium concentration is determined by gamma-spectrometry, ⁹⁰Sr and ⁹⁹Tc are determined by beta-counting. A one-liter sample can be processed and ready for counting within ten minutes. Using a 5-minute counting time, a detection limit of <50 pCi/l for ⁹⁹Tc or ⁹⁰Sr and ~50 pCi/l for ¹³⁷Cs has been achieved. Up to 10 liters of water have been processed for the analysis of ⁹⁹Tc and ¹³⁷Cs when lower limits of detection were required. The sampling and analysis system has been field tested at the Savannah River Site (SRS), Aiken SC, and the Hanford Site, Richland WA. The SRS H-area tank farm storm water runoff system was analyzed for ⁹⁰Sr and ¹³⁷Cs. Groundwater from the SX tank farm at the Hanford Site was analyzed for ¹³⁷Cs and ⁹⁹Tc. Groundwater from seeps below the 100-H area at Hanford was analyzed for ⁹⁰Sr and ⁹⁹Tc.     

Separation and concentration of technetium using a Tc-selective extraction chromatographic resin

For⁹⁹Tc separation from environmental samples, liquid-liquid extraction, ion-exchange chromatography and coprecipitation, have been described. Although these methods are removing matrix elements, some combinations of them is necessary for purification and concentration of Tc. Besides, the procedures are time-consuming and generally a week or more is needed to purify Tc in the samples. In this study, a novel extraction chromatographic resin for the separation and preconcentration of Tc from several kinds of solutions is described. The material is shown to retain Tc efficiently and selectively from these solutions. Sorbed Tc is readily recovered using 5 ml of 12M HNO₃ and the recoveries with^95mTc are more than 97% for all sample solutions.     

Characterization of 99mTc(CO)3-iminodiacetic acid (IDA) and its comparison with 99mTc-(IDA)2 using compounds for hepatobiliary scintigraphy

The organometallic precursor of fac-[^99mTc(CO)₃(H₂O)₃]⁺ has attracted much attention because of the robustness and small size of Tc(I)-tricarbonyl complexes compared to Tc(V) complexes and the good labeling affinity with a variety of donor atoms. Among various ligand systems, an iminodiacetic acid (IDA) was proven as a good chelating group to form a Tc(III)-compelx as well as has been shown its potential as a chelating system for fac-[^99mTc(CO)₃] precursor. In an attempt to confirm the similarity and the difference between ^99mTc(CO)₃-IDA and ^99mTc-(IDA)₂-complex, M(CO)₃-IDA (M = ^99mTc, Re) complexes of disofenin, mebrofenin and N-(3-iodo-2,4,6-trimethyl phenylcarbamoylmethyl) iminodiacetic acid were prepared, and the biological evaluation of ^99mTc(CO)₃-disofenin was performed. The ^99mTc(CO)₃-IDA complexes were prepared with a high radiolabeling yield (>98%) in a quantitative manner and showed a negative charge. The in vivo pharmacokinetic behavior of ^99mTc(CO)₃-disofenin showed a similar biological activity to ^99mTc-(disofenin)₂ in that those complexes were quickly cleared from the blood by the hepatocytes and excreted into the gallbladder and intestine. Accordingly, the ^99mTc(CO)₃-IDA derivatives of disofenin and mebrofenin might be used as hepatobiliary imaging agents. Since an IDA is a promising chelator for ^99mTc-based radiopharmaceutical and the biological properties of ^99mTc(CO)₃-IDA derivative shows similar to that of ^99mTc-complex, a biomolecule containing IDA can be freely radiolabeled with fac-[^99mTc(CO)₃]-precursor or ^99mTc. However, the radiolabeling efficiency and the biological behavior demonstrates the favorable properties of ^99mTc(CO)₃-IDA compound for the development of a new imaging agent.     

Determination of technetium-99 from complex matrix

This paper reports an approach that can be used for efficient separation and determination of ⁹⁹Tc (as pertechnetate) after contamination of the environment by nuclear materials. The samples were decomposed by fusion in a mixture of potassium hydroxide and potassium nitrate. After fusion, technetium remains as the pertechnetate anion (TcO₄ ^?). The technetium was isolated from the sample by technique combining solvent extraction, anion exchange, then, again, solvent extraction. After separation, ⁹⁹Tc was measured by isotope-dilution mass spectrometry with ⁹⁷Tc as spike. This method yielded nanogram detection limits for ⁹⁹Tc.     

Impact of Different [Tc(N)PNP]-Scaffolds on the Biological Properties of the Small cRGDfK Peptide: Synthesis,In Vitro and In Vivo Evaluations

Background: The [^99mTc][Tc(N)(PNP)] system, where PNP is a bisphosphinoamine, is an interesting platform for the development of tumor ‘receptor-specific’ agents. Here, we compared the reactivity and impact of three [Tc(N)(PNP)] frameworks on the stability, receptor targeting properties, biodistribution, and metabolism of the corresponding [^99mTc][Tc(N)(PNP)]-tagged cRGDfK peptide to determine the best performing agent and to select the framework useful for the preparation of [^99mTc][Tc(N)(PNP)]-housing molecular targeting agents. Methods: cRGDfK pentapeptide was conjugated to Cys and labeled with each [Tc(N)(PNP)] framework. Radioconjugates were assessed for their lipophilicity, stability, in vitro and in vivo targeting properties, and performance. Results: All compounds were equally synthetically accessible and easy to purify (RCY ≥ 95%). The main influences of the synthon on the targeting peptide were observed in in vitro cell binding and in vivo. Conclusions: The variation in the substituents on the phosphorus atoms of the PNP enables a fine tuning of the biological features of the radioconjugates. ws[^99mTc][Tc(N)(PNP3OH)]– and [^99mTc][Tc(N)(PNP3)]– are better performing synthons in terms of labeling efficiency and in vivo performance than the [^99mTc][Tc(N)(PNP43)] framework and are therefore more suitable for further radiopharmaceutical purposes. Furthermore, the good labeling properties of the ws[^99mTc][Tc(N)(PNP3OH)]– framework can be exploited to extend this technology to the labeling of temperature-sensitive biomolecules suitable for SPECT imaging.     

Preparation and Evaluation of Novel Folate Isonitrile 99mTc Complexes as Potential Tumor Imaging Agents to Target Folate Receptors

In order to seek novel technetium-99m folate receptor-targeting agents, two folate derivatives (CN5FA and CNPFA) were synthesized and radiolabeled to obtain [^99mTc]Tc-CN5FA and [^99mTc]Tc-CNPFA complexes, which exhibited high radiochemical purity (>95%) without purification, hydrophilicity, and good stability in vitro. The KB cell competitive binding experiments indicated that [^99mTc]Tc-CN5FA and [^99mTc]Tc-CNPFA had specificity to folate receptor. Biodistribution studies in KB tumor-bearing mice illustrated that [^99mTc]Tc-CN5FA and [^99mTc]Tc-CNPFA had specific tumor uptake. Compared with [^99mTc]Tc-CN5FA, the tumor/muscle ratios of [^99mTc]Tc-CNPFA were higher, resulting in a better SPECT/CT imaging background. According to the results, the two ^99mTc complexes have potential as tumor imaging agents to target folate receptors.     

Studies on the porphine labeled with <Superscript>99m</Superscript>Tc–pertechnetate

The aim of this research is to use acetylacetonate as a ^99mTc chelating agent label with porphyrin and evaluate its radiochemical and biological characteristics. Stannous chloride was used as a reductant to determine the chemical and biological characterization of ^99mTc-complexes from labeling porphine{4′,4′′,4′′′-(2lH,23H-Porphine-5,10,15,20-terayl)tetrakis-(benzoic acid), TPPB} with ^99mTc–pertechnetate. Instant thin layer chromatography (ITLC), size exclusion chromatography (SEC), paper electrophoresis, and UV/Vis spectrophotometry were used to evaluate chemical characterization. Finally, biodistribution and liver function tests were applied to evaluate biological characteristics. The results of this study show that the labeling efficiency of ^99mTc(acac)–TPPB was nearly 100% when using acetylacetone (acac) as a conjugator. Three major ^99mTc(acac)–TPPB complexes were separated by SEC, and all of them were hydrophilic. The UV-Vis spectra of ^99mTc(acac)–TPPB complexes closely resembled those of the TPPB, but the wave lengths of their peaks changed 430, 521, 556, 591 and 647 nm after complexation. The biodistribution study selected the liver as the target organ. The ^99mTc(acac)–TPPB complex may cause short-term liver injury. However, this injury can be repaired, and the reagent is quickly metabolized. Hence, the toxicity of the ^99mTc(acac)–TPPB complex is within an acceptable range, and making it a promising liver imaging agent.     

Technetium-99 in Fucusand seawater samples in the Finnish coastal area of the Baltic Sea, 1999

Liquid discharges of ⁹⁹Tc from the Sellafield nuclear facilities increased largely in the mid 90"s. These releases are transported to the Nordic sea areas by the ocean currents. Results of the ⁹⁹Tc activities along the Norwegian coastal areas and in the North Sea have been reported but then again, the spreading of ⁹⁹Tc into Baltic Sea has not been studied thoroughly. Fucus vesiculosus and seawater samples were collected in the summer 1999 from the Finnish coastal areas for measuring ⁹⁹Tc in the Baltic Sea area. A modified analytical method for measuring ⁹⁹Tc in the environmental samples was developed at that time. The method based on extraction chromatography and liquid scintillation measurement of ⁹⁹Tc. The ⁹⁹Tc concentration in the Fucus vesiculosus in the Finnish coast of the Baltic Sea varied from 1.6 to 11.6 Bq/kg (dry weight) being highest at the most northern sampling sites. These values were considerable lower than those in the Danish and Norwegian coasts. The variation in the concentrations observed are probably due to biological factors. The ⁹⁹Tc concentration in the Baltic Sea water studied was below 0.2 Bq/m³.     

Technetium(I) tricarbonyl complexes: potential precursors of the radiopharmaceuticals. Part II: phenethylbiguanide (phenformin)

The radiosynthesis of [^99mTc]-phenformin ([^99mTc]-1-phenethylbiguanide) complex and its suitability as precursor of the radiopharmaceuticals for the tumor imaging was assessed. Radiochemical purity of the [^99mTc]-complex was determined using radio-TLC and was studied by the HPLC with radiochemical detection, while its stability in challenge experiments. The results show, that due to the sufficient stability and lipophilicity of the complex, it fulfills our expectations for promising radiopharmaceutical precursor not only for the diagnostic agent, but also for the drug suitable for the oncological Auger electron therapy.     

Accumulation, elimination and retention of 99Tc by duckweed

This study deals with the accumulation dynamics of the long-lived fission product technetium (⁹⁹Tc) in duckweed. Duckweed serves as model for aquatic plants, because of its representative foliar uptake for ⁹⁹Tc. This study shows that ⁹⁹Tc is irreversibly accumulated and distributed over cytoplasm, chloroplasts and mitochondria. Autoradiography showed that ⁹⁹Tc was not transported to new biomass. Irreversible storage of ⁹⁹Tc in plant biomass means that steady-state situations cannot be interpreted as a balance between uptake and elimination of ⁹⁹Tc, but that ⁹⁹Tc continuously builds up in each single duckweed plant and overall Tc concentrations are averaged over new biomass.