Ascorbic acid as an eluent for99mTc in99Mo−99mTc generator system

A simple chromatographic procedure for clean separation of the important radionuclide,^99m Tc, in the equilibrium mixture,⁹⁹Mo−^99mTc, has been demonstrated. Separation of pure^99mTc has been achieved by preferential extraction of the radioisotope through an anion exchange resin column of Amberlite IRA-410 using Na-ascorbate solution at pH 7 as an eluent. The radiochemical purity of the separated radiotracer has been verified by taking recourse to γ-ray spectrometry. The potentiality of the developed procedure lies in the facts that the eluting agent, ascorbic acid, itself h got its own biomedical importance as Vitamin C and the concerned radioisotope can be obtained in both Tc(IV) and Tc(VII) states as per requirement for diagnostic purposes.     

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.     

Separation of no-carrier-added <Superscript>90</Superscript>Nb from proton induced natural zirconium target

Amongst various radionuclides of molybdenum, ⁹⁰Mo and ⁹⁹Mo have suitable β energy for clinical uses. In this paper we report separation of ⁹⁹Mo from ⁹⁹Mo-^99mTc equilibrium mixture. The liquid–liquid extraction technique has been employed using trioctylamine (TOA) diluted in cyclohexane as organic phase and HCl as aqueous phase. At 10⁻⁵ M HCl and 0.5 M TOA concentration ^99mTc quantitatively transferred to the organic phase leaving ⁹⁹Mo in the aqueous phase. The developed separation method is efficient and provides very high separation factor.     

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.     

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.     

A novel electrochemical <Superscript>99</Superscript>Mo/<Superscript>99m</Superscript>Tc generator

A novel electrochemical process to avail clinical grade ^99mTc from (n,γ)⁹⁹Mo has been demonstrated. The electrochemical parameters were optimized to maximize the ^99mTc yield with minimal ⁹⁹Mo contamination. ⁹⁹Mo/^99mTc generators containing up to 29.6 GBq (800 mCi) ⁹⁹Mo were developed and their performance were extensively evaluated for 10 days without changing the operating conditions. Very high radioactive concentration of ^99mTcO₄ ⁻ of acceptable quality, commensurate with hospital radiopharmacy requirements could be availed from the system with >90% yield. The compatibility of the product for the formulation of ^99mTc labeled radiopharmaceuticals such as ^99mTc-DMSA and ^99mTc-EC was found to be satisfactory in terms of high labeling yields. The proposed route represents an important step for enhancing the scope of accessing clinical grade ^99mTc from low specific activity (n, γ)⁹⁹Mo.     

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.     

Novel 99mTc labeled σ receptor ligand as a potential tumor imaging agent

A novel ^99mTc labeled complex, [N-[2-((2-oxo-2-(4-(3-phenylpropyl)piperazin-1-yl)ethyl) (2-mercaptoethyl)amino)acetyl]-2-aminoethanethiolato]Technetium(V) oxide (PPPE-MAMA’-^99mTcO) ([ ^99m Tc]-2) has been designed and prepared based on the integrated approach. The corresponding rhenium complex (PPPE-MAMA’-ReO)(Re-2) has been prepared and characterized. In vitro competition binding assays show moderate affinity of Re-2 towards σ₁ and σ₂ receptors with K _i values of 8.67 ± 0.07 and 5.71 ± 1.88 μmol, respectively. Planar images obtained at 0.5 h, 4 h, 20 h after i.v. injection indicate the accumulation of [ ^99m Tc]-2 in MCF-7 human breast tumor bearing mice at 20 h. Furthermore, the accumulation of [ ^99m Tc]-2 has been inhibited at 20 h after co-injection of [ ^99m Tc]-2 plus haloperidol (1 mg/kg). Biodistribution studies of [ ^99m Tc]-2 display an in vivo tumor uptake of 0.14% ± 0.01% ID/g at 24 h post i.v. injection with a tumor/muscle ratio of 6.02 ± 0.87. The above results suggest that [ ^99m Tc]-2, derived from a previously published lead compound, retains certain tumor uptake and affinity for σ receptors. [ ^99m Tc]-2 may be used as a basis for further structural modifications to develop tumor imaging agents with high affinity for σ receptors.     

Technetium-99 in “instant”99mTc-pertechnetate

The⁹⁹Tc-content in^99mTc-pertechnetate separated from⁹⁹Mo by distillation or extraction has been studied with a plastic scintillation detector. The identification of the measured activity was achieved by beta-spectrometry, chemical separation and half-life studies. The frequency distribution of the⁹⁹Tc/^99mTc-ratios in the different samples was observed to be log-normal. The most likely activity ratio was 0.4·10⁻⁶, the maximum value being 5·10⁻⁶. The specific activity of “instant” pertechnetate is approximately a factor of 60 lower than that normally recorded in pertechnetate derived from daily eluted column generators. The low specific activity of “instant” pertechnetate is primarily explained by the long time between separation and usage and secondly by the low yield of Tc in the distillation and extraction processes. In several of the “instant” pertechnetate solutions the carrier concentration exceeded the reductive capacity of the stannous ions in “kits” with small amounts of Sn(II) in usable form.     

Preparation and bioevaluation of <Superscript>99m</Superscript>Tc–carbonyl complex of guanine

The aim of this study is to prepare radiolabeled guanine with ^99mTc(CO)₃⁺ core. For this purpose, guanine has been radiolabeled with ^99mTc(CO)₃⁺ core. Quality control study of radiolabeled guanine molecule with ^99mTc(CO)₃⁺ core was performed by thin layer radio chromatography (TLRC) and high performance liquid radio chromatography (HPLRC). The results showed that the radiolabeling yield was quite high (94 ± 3%). Beside that ^99mTc(CO)₃–Gua complex has showed good in vitro stability during the 24 h period. Radiopharmaceutical potential of this complex was evaluated in Wistar Albino Rats. It was concluded that ^99mTc(CO)₃–Gua could be used as a nucleotide radiopharmaceutical for in vivo applications.     

Synthesis and radiolabelling of N-acetanilidoiminodiacetic acid analogues with MEK extracted99mTc

Labelling of N-(2,6-diethylacetanilido), N-(p-n-butylacetanilido,N-(p-methoxyacetanilido) and N-acetanilido-iminodiacetic acid analogues with^99mTc obtained by MEK extraction has been studied. The acetanilido IDA analogues were synthesized using the condensation reaction between nitrilotriacetic acid anhydride and the corresponding anilines. Conditions are described to label these four HIDA analogues using MEK extracted^99mTc with high and reproducible radiochemical purity.     

Separation of Tc(VII) from Tc(IV) by solvent extraction

The solvent extraction of Tc(IV) and Tc(VII) by isoamyl alcohol has been studied. The TcCl ₆ ²⁻ and TcO ₄ ⁻ ions are both extracted from 3M H₂SO₄ solution but hydrolyzed Tc(IV) species are not. This permits the separation of the two valence states of technetium. The air oxidation of carrier-free hydrolyzed^99mTc(IV) may be limited by the presence of⁹⁹Tc carrier in the same chemical form. Paper chromatography and electrophoresis were used to identify TcCl ₆ ²⁻ , TcO ₄ ⁻ and hydrolyzed species. It was also found that the hydrolyzed ReCl ₆ ²⁻ can reduce TcO ₄ ⁻ to Tc(IV).     

Characterization of99mTc/99Tc-hydroxycarboxylic acid chelates by high voltage electrophoresis without supporting material

Ion mobilities of different^99mTc- and⁹⁹Tc chelates prepared by reduction of pertechnetate by Sn(II) in the presence of citric, malic, tartaric, gluconic, and α-hydroxyisobutyric acid as ligands have been measured by means of electrophoresis without supporting material. All the chelates investigated proved to be anions in the pH range of 2–7. Both the Tc(V)- and Tc(IV) compounds with the same ligand including the^99mTc preparation show identical ion mobilities and dissociation characteristics.     

A simple technetium generator

A systematic study on the extraction of⁹⁹Mo and its daughter^99mTc by pure organic diluents and dinonylnaphthalinesulfonic acid (DNNS) is described. The aqueous phases used are H₂SO₄, HCl, KI and their binary mixture solutions. The effect of alcohols on the distribution coefficient has been investigated. As a result of the study, a simple and rapid generator is built for the production of pure^99mTc from⁹⁹Mo.     

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.     

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.     

The interaction of <Superscript>99m</Superscript>Tc with pyrimidine compounds

The reaction of ^99mTc of different oxidation states (+7, +4) with 2-thiouracil and 5-nitrobarbituric acid have been studied at different temperatures, pH and concentrations. The reaction mixtures have been analyzed at different times using thin layer chromatography (TLC) and a radio detector to show the peaks at the plates. ^99mTc is obtained from the Mo generators with oxidation state (+7). The use of SnCl₂ as a reducing agent gave ^99mTc with oxidation state (+4). It is very difficult to separate the complexes formed from the reactions in very small concentration. The percentage of ^99mTc and its oxidation state involved in the complexes can be determined. The labeling efficiencies (percentage of complex) in the reaction of ^99mTc⁺⁷ with 5-nitro-barbituric-acid increases mostly at pH  10. Both oxidation states of ^99mTc(+7, +4) can be detected at pH’s 4 and 10, but at pH  4, the reduced form ^99mTCO₂, is more pronounced. At pH  7 no complexes were detected and most of ^99mTc remains as ^99mTCO₄ ⁻ . By increasing the ligand concentration, the labeling efficiencies of the complex increases. For the reaction of ^99mTc of oxidation states (+4, +7) with 2-thiouracil at different temperatures and analytical times it is concluded that several complexes with different R_f values were observed in equilibrium and most of these complexes were unstable.     

On the behaviour of the daughter species resulting from chelates by beta-decay in separation processes

The specific phenomena accompanying the daughter nuclide formation by radioactive β-decay of complex parent compounds cause certain deviations from a thermodynamic distribution of daughter elements in separation procedures (e.g. in radionuclidic generators) and they are shown to complicate or, less probably, simplify their separation. A simple kinetic model has been proposed to explain such processes as the distribution of some daughter nuclides of fission products by solvent extraction with chelating compounds (systems of⁹⁹Mo−^99mTc and¹⁴⁴Ce−¹⁴⁴Pr with oxines).     

Bioevaluation of 99mTc(CO)3–Guanine in vitro and in vivo

The aim of this study is to examine biological behaviour of radiolabeled guanine with [Tc(CO)₃]⁺ core in vitro and in vivo. In vitro biological behavior of ^99mTc(CO)₃–Gua was evaluated on Lung (A-549), Breast (MCF-7), Colonic (Caco) carcinoma cell lines and normal human bronchial epithelial (NHBE). ^99mTc(CO)₃–Gua compound showed high uptake on A-549 cell line when compared to NHBE cell line. Biodistribution characteristics of ^99mTc(CO)₃–Gua was evaluated using New Zeland Rabbits. Scintigraphic results showed that a high level of radioactivity was observed in the lungs and liver shortly after administration of the ^99mTc(CO)₃–Gua and excretion takes place via both renal and hepatobiliary route. It was concluded that ^99mTc(CO)₃–Gua could be used as a nucleotide radiopharmaceutical for imaging purposes.     

Determination of molybdenum in biological materials by neutron activation

A method of the determination of molybdenum in biological materials by neutron activation is described. The method is based on the γ-spectrometric measurement of^99mTc after radiochemical separation of the latter by substoichiometric extraction with tetraphenylarsonium chloride using rhenium as inactive carrier. The method has been tested with reference materials.