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.     

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.     

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.     

Comparison of a radiation counting method and ICP-MS for the determination of99Tc in environmental samples

Results of⁹⁹Tc measurements between radiation and non-radiation counting methods were compared using four radiation sources for which⁹⁹Tc has been previously determined with a gas-flow proportional counter or a GM counter. Each⁹⁹Tc source consisted of a stainless steel planchet bound by mylar films. Seaweeds collected from the Irish Sea were analyzed and⁹⁹Tc was electroplated on the planchet. The⁹⁹Tc in each sample was separated and measured again by inductively coupled plasma mass spectrometry (ICP-MS). Tc was continuously removed from each sample with 2M HNO₃ and 2M NaOH. After the solution containing Tc was adjusted to 0.1M HNO₃, Tc was extracted on a novel extraction chromatographic resin to separate it from Ru. The total recoveries for Tc on the planchet samples were almost the same with an average of 91%. The results of⁹⁹Tc measurements by both radiation and non-radiation counting methods agreed well with each other.     

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.     

The stability of99mTc phosphorus compounds in plasma both in vivo and in vitro

The in vivo and in vitro stability of^99mTc hydroxyethlylidene diphosphonate, 99^mTc methylenediphosphonate and^99mTc pyrophosphate in plasma has been studied using paper chromatographic technique as the analytical tool. The results indicate that the amounts of^99mTc activity found both at the origin and R_f range of^99mTcO₄ ^? for in vivo experiments are slightly greater than those for either in vitro or control experiments. However, this amount of^99mTc activity represents about 0.16–0.4% of the injected dose. Therefore, it is suggested that^99mTc phosphorus radiopharmaceuticals are stable in vivo and neither oxidation nor hydrolysis of these bone imaging agents occurs in the blood.     

Separation and purification of 99mTc from 99Mo produced by electron linear accelerator

The medical radionuclide ⁹⁹Mo was produced by the ¹⁰⁰Mo(γ,n) reaction using bremsstrahlung photons generated by an electron linear accelerator. The amount of ⁹⁹Mo produced was compared to that predicted by calculation using the particles and heavy ion transport code system. From the ⁹⁹Mo produced, highly pure ^99mTc was separated using the so-called technetium master milker, and the chemical yield of ^99mTc was 83–99 %. The installation of a new complex using this method and the electron linear accelerator with the preferable specification was suggested, and a possibility to supply the demand of ^99mTc was discussed and shown.

     

Determination of low-level99Tc in environmental samples by high resolution ICP-MS

An analytical method has been developed for the determination of low-level⁹⁹Tc in environmental samples by High Resolution ICP-MS. The method consists of leaching of⁹⁹Tc by HNO₃ and separation by three different solvent extractions with 30% TOA-xylene, MEK, and cyclohexanone. Finally, purification of⁹⁹Tc was made by using an anion exchange resin column to reduce dissolved solids content. The final solution was adjusted to 1M HNO₃ for introducing into the HR-ICP-MS. The accuracy and precision of the method was confirmed to be satisfactory by applying this technique to the determination of⁹⁹Tc in IAEA marine algae sample (AG-B-1). Measurements of⁹⁹Tc using 0.5–2.5 g of sediment samples from the Irish Sea, UK, were successfully performed by the present method.     

Radiosynthesis and evaluation of novel [99mTc(I)]+ and [99mTc(I)(CO)3]+ complexes with a 4-nitroimidazole isocyanide for imaging tumor hypoxia

[^99mTc(I)]⁺ and [^99mTc(I)(CO)₃]⁺ complexes with isocyanide exhibit high stability, which makes them suitable platforms to develop novel ^99mTc radiopharmaceuticals. To develop novel ^99mTc radiotracers for imaging hypoxia, in this study, a novel L ligand (4-nitroimidazole isocyanide derivative) was synthesized and labelled using [^99mTc(I)]⁺ core and [^99mTc(I)(CO)₃]⁺ core to produce [^99mTc(L)₆]⁺ and [^99mTc(CO)₃(L)₃]⁺ with high yields. To verify the structure of the ^99mTc complexes, corresponding rhenium analogues were synthesized and characterized. Both of the ^99mTc complexes were stable and hydrophilic. in vitro cellular uptake results showed they could exhibit good hypoxic selectivity. The evaluation of biodistribution in mice bearing S180 tumors indicated both of them could accumulate in tumor. Between them, [^99mTc(L)₆]⁺ exhibited higher tumor uptake and tumor/non-target ratio than [^99mTc(CO)₃(L)₃]⁺. Further, single photon emission computed tomography (SPECT) imaging studies of [^99mTc(L)₆]⁺ indicated an obvious accumulation in tumor and the value of the region-of-interest (ROI) ratio of the uptake for the tumor site to the corresponding non-tumor region was 5.64 ± 0.52. The above results suggested [^99mTc(L)₆]⁺ would be a potential tracer for imaging tumor hypoxia.     

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.     

Determination of calibration curves for <Superscript>131</Superscript>I in thyroid tumour metabolic radiotherapy and other radionuclides used in SPECT imaging

Large columns containing aluminum oxide (Al₂O₃) or gel (e.g. zirconium molybdate) are needed to prepare ⁹⁸Mo(n,γ)⁹⁹Mo→^99mTc column chromatographic generators that results in large elution volumes containing relatively high ⁹⁹Mo impurity and low concentrations of ^99mTc. The decrease in radioactive concentration or specific volume concentration of ^99mTc places a limitation on some pharmaceutical kits (DTPA, MIBI, ECD, etc.) or clinical procedures. We report on the post elution concentration of ^99mTc using in house prepared lead cation-exchange and alumina columns. Using these columns high bolus volumes (10–60 mL 0.02M sodium sulfate) of ^99mTc can conveniently be concentrated in 1 mL of physiological saline. This approach also works very effectively to prepare high specific volume solutions of ^99mTc-pertechnetate from a fission based ⁹⁹Mo/^99mTc generator in the second week of its normal working life.     

Synthesis and biological distribution of 99mTc–norfloxacin complex, a novel agent for detecting sites of infection

The optimization of the radiolabeling yield of ciprofloxacin analogous, norfloxacin, with technetium-99m (^99mTc) was described. Dependence of the labeling yield of ^99mTc–norfloxacin complex on the concentration of norfloxacin, SnCl₂·2H₂O content, pH of the reaction mixture and reaction time was studied. Norfloxacin was labeled with ^99mTc at pH 3 with a labeling yield of 95.4% by using 5 mg norfloxacin, 50 μg SnCl₂·2H₂O and 30 min reaction time. The formed ^99mTc–norfloxacin complex was stable for a time up to 3 h. Biological distribution of ^99mTc–norfloxacin complex was investigated in experimentally induced inflammation rats using Staphylococcus aureus (bacterial infection model) and heat killed Staphylococcus aureus and turpentine oil (sterile inflammation model). In case of bacterial infection, the T/NT value for ^99mTc–norfloxacin complex was found to be 6.9 ± 0.4 which was higher than that of the commercially available ^99mTc–ciprofloxacin under the same experimental condition.     

Comparison of ‘classic’ Tc-DTPA, Tc(CO)3-DTPA and Tc(CO)2(NO)-DTPA

Diethylenetriamine pentaacetic acid (DTPA) was labeled with ^99mTc in three different ways, resulting in ‘classic’ ^99mTc-DTPA, ^99mTc(CO)₃-DTPA and ^99mTc(CO)₂(NO)-DTPA. The biodistribution of the formed DTPA-complexes was studied in mice with a special emphasis on the behavior of the novel tricarbonyl and dicarbonyl-nitrosyl complexes, which was clearly differing from that of ‘classic’ ^99mTc-DTPA. The conversion of a Tc-tricarbonyl complex to a Tc-dicarbonyl-nitrosyl complex using NO⁺ reagents offers a synthetic tool for preparing a novel class of ^99mTc labeled compounds.     

A simple and sensitive separation technique of 99Mo and 99mTc from their equilibrium mixture

The present work describes a simple and inexpensive separation method of ⁹⁹Mo from the equilibrium mixture. The liquid–liquid extraction technique has been employed to separate ⁹⁹Mo and ^99mTc using triisooctylamine (TIOA). The ⁹⁹Mo and ^99mTc were quantitatively separated out in 2 M TIOA with tripled distilled water; ^99mTc was back extracted from TIOA organic phase to aqueous phase by 0.1 M DTPA. The species information or indirect speciation of molybdenum was also established by the extraction profile of the molybdenum.     

Activation analysis for technetium-99 by the use of a neutron-excitation reaction

The formation of^99mTc was observed when⁹⁹Tc was irradiated by reactor neutrons as a result of the⁹⁹Tc(n, )^99mTc reaction. A good linearity was observed between the activities of^99mTc produced and⁹⁹Tc irradiated. The cross section of the excitation reaction was estimated to be 0.24 b. The application of the nuclear excitation reaction to the activation analysis for low level⁹⁹Tc was studied.     

Separation of99mTc from parent99Mo by solid-phase column extraction as a simple option for a new99mTc generator concept

Evidence is obtained to show that the liquidliquid extraction separation of^99mTc from⁹⁹Mo with methyl ethyl ketone, methyl propyl ketone and methyl isobutyl ketone can be transformed into a solid-phase column extraction procedure. The aqueous alkaline⁹⁹molybdate solution is immobilized on a column of a granular large-pore diatomaceous earch support, which is the neluted with the abovementioned extractants. Rapid and clean separation of^99mTc can be with all three solvents. The^99mTc can be back-extracted from the organic phase on a column filled with distilled water /or saline/ loaded granular diatomaceous earth /Extrelut^®/. The possibility of using the abovementioned procedure as a basis for a new^99mTc/⁹⁹Mo generator concept is envisaged.     

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.     

Effective synthesis of Tc tricarbonyl complexes by microwave heating

Technetium-99m (^99mTc) is one of the most frequently used nuclides for single-photon emission computed tomography (SPECT) imaging because of its radiochemical characteristics, such as gamma emission of suitable energy (141 keV) and adequate half-life (6.01 h). Although triaquatricarbonyl ^99mTc cation ([^99mTc(CO)₃(H₂O)₃]⁺) has several advantages as a ^99mTc-labeling agent, e.g., compact chelate size, chelate stability, and simplicity of preparation, its synthetic protocols should be improved. Because microwave heating is a convenient method for synthetic reactions, we studied the effect of microwave irradiation on the synthesis of ^99mTc tricarbonyl complexes. We found several factors beneficial for the preparation of nuclear medicines. In particular, microwave heating promoted one-pot syntheses of ^99mTc tricarbonyl chelates in a short time. In addition, the ^99mTc tricarbonyl complex could be obtained using low concentrations of ligands.     

Synthesis and biodistribution of two novel 99mTc “3+1”mixed ligand complexes as potential brain perfusion agents

The research in the last decade has been mainly aimed at the development of technetium-99m radiopharmaceuticals, among which are the “3+1”mixed ligand complexes. Two novel [^99mTc]“3+1”mixed ligand complexes each carrying the tridentate ligand, the N-(o-Methylthiophenyl)ethylenediamine or the N-(o-Methylthiophenyl)-b-mercaptoacetamide in combination with monothiolate coligand were produced using stannous chloride as reductant and glucoheptonate as transfer ligand. The identification of [^99mTc]-6 and [^99mTc]-7 was established by thin layer chromatography. The radiochemical purity of two complexes was over 90%. Biodistribution data in mice showed that both [^99mTc]-6 and [^99mTc]-7 can penetrate the intact blood-brain barrier and exhibited retention in mice brain. The brain uptakes (%ID/g) were 1.76, 1.17, 0.90 and 0.68, 0.38 ,0.37 at 2, 30, and 60 minutes i.v. postinjection for [^99mTc]-6 and [^99mTc]-7, respectively. Examples in this report comfirm us that it is promising to develop ^99mTc complexes as potential brain perfusion agents based on modifying either the tridentate or the monodentate ligands. This revised version was published online in August 2006 with corrections to the Cover Date.     

Practicality of Tetragonal Nano-Zirconia as a Prospective Sorbent in the Preparation of 99Mo/99mTc Generator for Biomedical Applications

The feasibility of using tetragonal nano-zirconia (t-ZrO₂) as an effective sorbent for developing a ⁹⁹Mo/^99mTc chromatographic generator was demonstrated. The structural characteristics of the sorbent matrix were investigated by different analytical techniques such as XRD, BET surface area analysis, FT-IR, TEM etc. The material synthesized was nanocrystalline, in tetragonal phase with an average particle size of ~7 nm and a large surface area of 340 m² g^?1. The equilibrium sorption capacity of t-ZrO₂ is >250 mg Mo g^?1. The present study indicates that ⁹⁹Mo is both strongly and selectively retained by t-ZrO₂ at acidic pH and ^99mTc could be readily eluted from it, using 0.9% NaCl solution. A 9.25 GBq (250 mCi) t-ZrO₂ based chromatographic ⁹⁹Mo/^99mTc generator was developed and its performance was repeatedly evaluated for 10 days. ^99mTc could be eluted with >85% yield having acceptable radionuclidic, radiochemical and chemical purity for clinical applications. The compatibility of the product in the preparation of ^99mTc labeled formulations such as ^99mTc-EC and ^99mTc-DMSA was evaluated and found to be satisfactory.