Preparation and characterization of an extraction chromatography column for technetium separation based on Aliquat-336 and silica gel support

An extraction chromatographic material based on Aliquat-336 anchored on hydrophobized silica gel support was prepared as an ion exchanger. The prepared material appeared to be suitable for the separation of ⁹⁹Tc from environmental matrices in column application. The properties of the material, sorption characteristic and distribution coefficient of ^99mTcO₄ ^-in various media were studied. The prepared sorbent was conditioned by washing with nitric acid. The solution containing ^99mTcO₄ ^- in 0.1M HNO₃ was passed through the column. Tc was eluted from the column by 8M HNO₃. The flow rate was 0.4 ml/min. The chemical yield of technetium during the separation process was determined using ^99mTc tracer and gamma measurement. The sorption recovery of Tc from the prepared sorbent with 0.1M HNO₃ solution was more than 98%, and the desorption recovery from the column using 8M HNO₃ varied between 92-96%. It was found that the prepared sorbent is suitable for the separation of technetium from environmental matrices and radioactive wastes. This revised version was published online in July 2006 with corrections to the Cover Date.     

The determination of technetium-99 in seawater and marine algae

Technetium-99 is preconcentrated from acidified seawater containing a trace of bromine by adsorbing it as the pertechnetate ion on the anion exchanger Duolite A101D. After elution with 4 M nitric acid, it is purified from other radionuclides by scavenging with hydrous iron(III) oxide and extracting from 5 M sodium hydroxide medium into methyl ethyl ketone. The organic phase is then evaporated and technetium is electrodeposited from oxalic acid medium onto a bronze disc and counted with a low background β-counter. Overall recovery is > 90% and the precision is ±0.2 pCi l^-1 at a technetium level of 0.6–1.0 pCi l^-1. Concentrations of the radionuclide in the central Irish Sea were found to lie in the range 0.4–2 pCi l^-1. The same analytical scheme can be used for determining the element in nitric acid digests of marine algae.     

Development of a rapid HPLC method for quantification of the copper tetramibi tetraflourborate in a kit for preparation of Technetium 99 m Sestamibi Injection

Radiopharmaceuticals are radioactive compounds that can be used for diagnostic and therapeutic purposes. Technetium (99mTc) Sestamibi is the most commercialized radiopharmaceutical in the world. It includes a coordination complex consisting of the radioisotope 99 m technetium bound to six copper tetramibi tetrafluorborate ligands, and is mainly used to image the myocardium via scintigraphy. As radiopharmaceuticals are regarded as drugs, they are subject to the same regulations; therefore, the objective of this study was to develop a quantification method for the active pharmaceutical ingredient before their complexation with the radioisotope by employing high‐performance liquid chromatography (HPLC) methodology. A simple and efficient method (retention time = 2.5 min) was developed and validated for copper tetramibi tetrafluorborate in the final product using a buffer and organic solvent mixtures (ACN–methanol–ammonium sulfate buffer) and a C₁₈ column. The analytical protocol was fast, taking around 30 min until evaluation of results. The validation parameters were evaluated with satisfactory results: in terms of linearity r > 0.99 (160–240 μg/mL) and no deviation was observed. The RSD of precision was <5%, and an average recovery of 99% was observed for accuracy. The proposed method was thus considered adequate for routine analysis in the pharmaceutical industries.     

Synthesis and evaluation of analogues of HYNIC as bifunctional chelators for technetium

6-Hydrazinonicotinic acid (HYNIC, 1) is a well-established bifunctional technetium-binding ligand often used to synthesise bioconjugates for radiolabelling with Tc-99m. It is capable of efficient capture of technetium at extremely low concentrations, but the structure of the labelled complexes is heterogeneous and incompletely understood. In particular, it is of interest to determine whether, at the no-carrier-added level, it acts in a chelating or non-chelating mode. Here we report two new isomers of HYNIC: 2-hydrazinonicotinic acid (2-HYNIC, 2), which (like 1) is capable of chelation through the mutually ortho hydrazine and pyridine nitrogens and 4-hydrazinonicotinic acid (4-HYNIC, 3), which is not (due to the para-relationship of the hydrazine and pyridine nitrogens). LC-MS shows that the coordination chemistry of 2 with technetium closely parallels that of conventional 1, and no advantages of one over the other in terms of potential labelling efficiency or isomerism were discernable. Both 1 and 2 formed complexes with the loss of 5 protons from the ligand set, whether the co-ligand was tricine or EDDA. Ligand 3, however, failed to complex technetium except at very high ligand concentration: the marked contrast with 1 and 2 suggests that chelation, rather than nonchelating coordination, is a key feature of technetium coordination by HYNIC. Two further new HYNIC analogues, 2-chloro-6-hydrazinonicotinic acid (2-chloro-HYNIC, 4a) and 2,6-dihydrazinonicotinic acid (diHYNIC, 5) were also synthesised. The coordination chemistry of 4a with technetium was broadly parallel to that of 1 and 2 although it was a less efficient chelator, while 5 also behaved as an efficient chelator of technetium, but its coordination chemistry remains poorly defined and requires further investigation before it can sensibly be adopted for (99m)Tc-labelling. The new analogues 4a and 5 present an opportunity to develop trifunctional HYNIC analogues for more complex bioconjugate synthesis.     

Methodological studies of the determination of 99Tc in matrix-rich environmental samples

A few experiments testing technetium behavior at different conditions for complex matrixes (soils, sediments) were performed. It was confirmed that the incineration of samples soaked with ammonia can be done without technetium losses. Next, for the precipitation of iron(III) hydroxide at different pH levels, the degree of co-precipitation of technetium was studied. It can be helpful during purification of very matrix-rich and massive samples. Finally the technetium and rhenium fractionation during separation of technetium from the environmental samples was studied. This test clearly showed limitations for using Re as yield tracer during ⁹⁹Tc analyses in case of mineral matrixes.     

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.     

Direct analysis of whole blood by internal surface reversed-phase chromatography: an examination of the binding and metabolism of technetium dioxime complexes.

We have developed a method using internal surface reversed-phase (ISRP) packing for rapid on-line separation of small hydrophobic compounds from cellular whole blood components. This is achieved by the use of 75-microns ISRP chromatographic material packed into a small high-performance liquid chromatographic (HPLC) column, in conjunction with column switching. We have applied this analytical method to study the in vitro metabolism of 99mTc-BATO (boronic acid adducts of technetium dioxime) cerebral and myocardial perfusion tracers in whole blood. The results from the ISRP procedure were compared with a conventional centrifugation method of analysis. This novel HPLC methods provides a rapid, convenient and reliable method for the analysis of radioactive and non-radioactive lipophilic components in whole blood.     

染料壳聚糖微球的制备及其对牛血清白蛋白(BSA)吸附性能的研究

采用反相悬浮交联法制备壳聚糖微球,对微球进行羟丙基氯化及氨基化,并偶联色素配体Cibacron Blue F3GA,得到一种新型染料亲和吸附剂.以牛血清白蛋白(BSA)为目标蛋白,考察了该染料亲和吸附剂的吸附性能,发现其对BSA有较高的吸附量(95.2mg/g),吸附行为满足Langmuir吸附等温式.负载牛血清白蛋白的微球容易洗脱,洗脱率高达99％.     

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.     

99mTc generator with hydrated MnO2 as adsorbent of 99Mo

An ^99mTc generator with MnO₂ as adsorbent of ⁹⁹Mo was investigated. Through batch experiments the retention of ⁹⁹Mo onto MnO₂was studied as a function of the shaking time and the pH value of the ⁹⁹Mo solution. It was found that ⁹⁹Mo showed a retention of 100% onto MnO₂ at the pH range from 3 to 11, and the equilibrium distribution was reached in less than 10 minutes. In column experiments the retention of ⁹⁹Mo onto MnO₂ was also high: 99.72%. In this case, the pH of the utilized ⁹⁹Mo solution was 5. The ^99mTc could be eluted from the MnO₂-⁹⁹Mo column by using either distilled water with a pH of 5 or an aqueous solution of 0.9% NaCl. With the saline solution, the ^99mTc elution yields were higher than 80%, and only one aliquot of 5 ml was needed to get these yields. The best results were obtained when the column was packed with 1 g of MnO₂. The water and the saline solution were passed through the column at a rate of 1.25 ml/min.     

Preparation of technetium-99m-humic complex by ligand exchange from hexakis (thiourea-S)technetium(III) complex

The preparation of technetium-99m-humic complex without presence of any metal reductant was studied. For the preparation of Tc-HA complex by ligand substitution hexakis(thiourea-S)technetium(III) complex was used as a precursor. Ligand exchanging reaction was studied with two different humate/thiourea concentration ratios. After mixing of [^99mTc(tu)₆]³⁺ complex with natrium humate under a nitrogen atmosphere a formation of technetium humate wasobserved. The determination of reaction products was performed by combination of gel and paper chromatography. Reaction yields are dependent on humate/thiourea concentration ratio and reaction time. Tc-HA complex was obtained with the highest yield of 62%. Reaction mixture also contains a technetium dioxide as a side product of exchanging reaction and other technetium species, which are also discussed. Oxidation state of technetium in prepared Tc-HA complex is apparently unchanged.     

The 4-tert-butylphenyl group as a simple tag for solution phase synthesis

A solution phase synthesis strategy was investigated using 4-tert-butylphenyl group as the tag and a beta-cyclodextrin column as the affinity chromatographic support for the isolation of compounds containing the tag. It was found that compounds containing the tag have significantly longer retention times on the beta-cyclodextrin column than those compounds that do not have such a tag. The tag is chemically inert and can be introduced onto and removed from target compounds readily. This solution phase synthesis method was applied to the synthesis of some simple amino acid derivatives.     

Contributions to the coordination chemistry of technetium

The radionuclide^99mTc is widely used in nuclear medical diagnostics. Radiopharmaceuticals containing coordination compounds labeled with^99mTc⁴⁺ or^99mTc⁵⁺ can be rapidly prepared from pertechnetate eluted from a⁹⁹Mo/^99mTc generator. For the optimization of the imaging agent it is essential to determine the exact chemical structure of the Tc complex. This can be achieved by synthesizing macroscopic amounts of the analogous long-lived^99gTc compound and by its analysis by appropriate spectroscopy methods. We have successfully synthesized and characterized new technetium complexes with amino acids and also with ligands containing nitrogen, oxygen and sulfur atoms.     

Estimation of disaccharides in plasma and urine by gas-liquid chromatography

A technique for the estimation of disaccharides in plasma and urine using gas-liquid chromatography is described. The procedure involves the formation of trimethylsilyl derivatives followed by injection of the reaction mixture directly onto the column. The method is precise, linear over a wide range and gives recoveries of 93--99%. The limit of sensitivity is 80 micrograms per 100 ml, but with modification of the volumes used, levels of 40 micrograms per 100 ml may be quantitated.     

限进介质烷基-二醇基硅胶(ADS)的制备

 烷基 二醇基硅胶 (ADS)系限进介质的一种 ,可用于含生物大分子的复杂生物样品的直接进样与分析。一种新的、非常经济的方法可用于烷基 二醇基硅胶的制备。首先 ,将γ 环氧丙基氧丙基三甲氧基硅烷基键合至微孔硅胶上 (粒度 5 μm ,孔径 6nm)以制备环氧基硅胶 ,再令环氧基硅胶与硬脂酸在有机溶液中进行反应以制备酯型十八烷基反相填料。将制得的反相填料填充至色谱柱中 ,并令含有酯酶的溶液通过色谱柱。通过酶解作用可将硅胶表面的酯基除去 ,而硅胶的内孔表面仍保持疏水特性不变 ,这是由于硅胶上的小孔对酶分子具有体积排除作用。     

Neutron flux characterization of the beam port of the Missouri University of Science and Technology Reactor

Alpha spectrometry is used for qualitative and quantitative analysis of actinides in biological and environmental samples. This technique requires a thin, homogenous and carrier-free deposit. Numerous methods for source preparation are electrolytic deposition, spontaneous deposition, micro-precipitation, direct evaporation, vacuum sublimation, etc. The most widely used method for preparation of actinides for alpha spectrometry is electro-deposition of actinides onto a stainless steel planchette. This procedure is time consuming, requires elaborate equipment and is expensive. Micro-precipitation method on the other hand is comparatively faster and more reliable. Thus, the present study was taken-up to optimize various parameters for rapid alpha source preparation of actinides by micro-precipitation method.

     

Comparison of the TEVA-Spec resin and liquid-liquid extraction methods for the separation of technetium in soil samples

When ICP-MS is used for⁹⁹Tc measurements, elements which interfere with⁹⁹Tc counting should be removed. In this study, a separation method using a novel chromatographic resin (TEVA·Spec^® resin) was compared with a liquid-liquid extraction (LLX) method for separation and concentration of⁹⁹Tc which was trapped in a solution after combustion of environmental soil samples. The results showed that Tc could be separated from Ru at high recoveries with both separation methods. Molybdenum, however, was not removed by LLX, while more than 99% of Mo in soil samples were removed by TEVA·Spec resin.     

On the separation of molybdenum and technetium crown ether as extraction agent

Separation of⁹⁹Mo and^99mTc can be performed with high selectivity using the crown ether 2,3,11,12-dibenzo-1,4,7,10,13,16-hexaoxacyclooctadeca-2,11-diene /DB18C6/ diluted with nitrobenzene. The high efficiency is attributed to the rather low extractability of molybdenum as compared with that of technetium.     

EPR on trichloro-nitrosyl-bis(dimethylphenylphosphine)technetium(II) TcCl3(NO)(PMe2Ph)2

The d⁵ low-spin Tc(II) complex trichloro-nitrosyl-bis(dimethylphenyl-phosphine)technetium(II) was studied by EPR at 295 ≥ T ≥ 27.2 K. In the room-temperature spectrum well-resolved ⁹⁹Tc hyperfine splitting is observed indicating a ground state for the unpaired electron which is well separated from other orbital states. At low temperatures the spectrum can be fitted by an axial spin Hamiltonian. The analysis of the ⁹⁹Tc hyperfine splitting shows remarkable covalent interactions with the “in-plane” ligands. The ³¹P superhyperfine splitting observed was used to get information about the overall spin density distribution in the molecular orbital of the unpaired electron.     

Studies on the solvent extraction of technetium from thiocyanate solutions in mineral acids

Technetium-99m, separated from fission molybdenum-99, has been studied as a component of liquid-liquid phase distribution equilibria. 5-(4-Pyridyl)nonane in a carrier diluent, benzene, has been used to study the distribution of the nuclide from thermodynamically suitable aqueous phases of electrolytes with and without sterically receptive thiocyanate ions. Efficient extraction of the metal can be accomplished in a variety of aqueous phase compositions. The separation factors with respect to molybdenum, under certain experimental conditions, are fairly high. The data have been utilized to effect clean separations of technetium from molybdenum.