Statistical analysis of the results of99mTc-MDP quality control

The methods used for control of radiochemical purity of^99mTc-MDP are presented. TLC method on silica gel, developed with methanol and acetone (11 v/v), was convenient for determination of^99mTcO ₄ ^– with the content of 2.6±1.2%. The reliable results on detection of^99mTc hydrolyzate (2.2±1.3%) and for another^99mTc-MDP complex (13.2±2.8%) were obtained by application of ITLC (SA), developed with Sn-MDP. By Sephadex G-25 column chromatography (1.5 cm×5 cm) the separation of^99mTcO ₄ ^– was not achieved. The range of normal^99mTc-MDP biodistribution values in the organs of experimental animals have been determined. The mean value of bone distribution was 8.4±1.13%/g, in muscles 0.071±0.033%/g, while uptake in liver and kidneys was below 5%. Chi-square test and P show that the results on biodistribution of^99mTc-MDP in liver, bones and muscles are arranged around their mean values, which is statistically allowed.     

Comparative study of quality control procedures for99mTc radiopharmaceuticals

Paper and TLC chromatographic methods have been evaluated for the control of the labeling and stability of eight Tc-radiopharmaceuticals. The different supporting media and eluents have been studied and the most suitable methods have been classified according to their usefulness, reliability and rapidity. Moreover the artefacts encountered have been investigated. Alumina is found not suitable for its interference with TcO ₄ ^– . Acetate buffer seems to be labeled by TcHR inducing frequently subsequent smearings. Methyl ethyl ketone is optimal for the quantification of TcO ₄ ^– except in Tc-HIDA. TcHR never migrates as well as Tc-S Coll, Tc-MAA and Tc-HSA. The well-defined separation of TcO ₄ ^– and TcHR from the radiopharmaceutical often requires a two-step method.Throughout this paper, the symbol Tc will be used to represent technetium-99m.     

Labeling of polyaminomacrocyclic ligands BY99mTcO 4 − reduction and exchange reactions

The cationic^99mTc-complexes of 1,4,8,12-tetraazacyclopentadecane (15-ane-N₄), 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane (Me₄cyclam) and 1,4,7,10,13,16-hexaazacyclooctadecane (hexacyclen) are obtained in yields higher than 80% by^99mTcO ₄ ^– reduction at pH 12. The electrophoretic and chromatographic analyses show that these ligands form structurally similar complexes. Efficient labeling of 15-ane-N₄ (>95%) is obtained by the exchange reaction with^99mTc-citrate,^99mTc-ENDA and^99mTc-HBA at pH 12. The labeling yield of hexacyclene is 70% and 85% following the reaction with^99mTc-ENDA and^99mTc-HBA and^99mTc-citrate, respectively. The labeling of Me₄cyclam is very poor (about 10%) except starting from^99mTc-citrate (55%). The results are compared wint the available data for well characterized [TcO₂L]⁺ complexes.     

A new technetium(V)-2-thiohydantoin complex

Summary A new 2-thiohydantoin ^{99Tc v} complex was prepared by the direct reduction of TcO ₄ ^– with alkaline Na₂S₂O₄ in the presence of an excess of the ligand, and characterized by spectroscopy. Reversed phase HPLC on lichrosorb-Rp-18 showed the complex to be pure; electrophoresis measurements showed it to be neutral. The complex was H₂O soluble.     

Synthesis,radiochromatography and biodistribution of99mTc-dimethylphosphinoethane (DMPE) complexes

The title complexes were prepared from no-carrier-added^99mTc–TcO ₄ ^– and the air-sensitive reducing ligand DMPE under argon in ethanol-water. At acidic pH [Tc(III)Cl₂ dmpe₂]⁺ was formed, while alkaline pH led to the formation of [Tc(I)dmpe₃]⁺. About 150°C and at least 10^–3M DMPE was needed to achieve over 95% yield in less than 1 hour, otherwise the [Tc(V)O₂dmpe₂]⁺ intermediate was present. Electrophoresis demonstrated the unit positive charge and reversed-phase ion-pair HPLC provided separation and identification of^99mTc-products by direct comparison with known⁹⁹Tc-complexes. In rats the^99mTc-complexes were excreted by kidneys and liver and reached high heart/blood but only low heart/lung and heart/liver ratios. In dogs satisfactory myocardial scintigrams were obtained in spite of high liver activity.     

Adsorption of pertechnetate ion on active carbon from acids and their salt solutions

The adsorbability of pertechnetate ion (TcO ₄ ^– ) reached 96% for an active carbon at the 0.1 g/50 ml concentration level, increasing with diminution of acid and its salt concentrations, and depending on the type of anions present. With constant anion concentration, TcO ₄ ^– adsorbability rose with decreasing pH in the acidic region, followed in the region around neutrality by a plateau, and in the basic region by an appreciable decline of TcO ₄ ^– adsorbability. In the acidic region, part of once-adsorbed TcO ₄ ^– appeared to be displaced by other anions. Reversibility was noted between the adsorption and desorption of TcO ₄ ^– .     

99mTc complexes of 1,3-propanedithiol derivatives

The labelling of 1,3-n alkylpropanedithiols and of 15-/1,3-dimercapto 2-propyl/ pentadecanoic acid by^99mTc has been performed by an exchange reaction with the hexachlorotechnetate ion^99mTcCl ₆ ^2– and by reduction of^99mTcO ₄ ^– with Sn/II/ in the presence of the ligand. The biological distribution of the exotechnetium complexes obtained by the latter method in mouse does not reveal a high tropism of these labelling compounds in relation to a particular tissue.     

Ligand exchange and solvolytic reactions of99mTcBr 6 2− in non-aqueous media

Prior work had documented that^99mTcCl ₆ ^2– could undergo ready ligand exchange reaction under non-aqueous condition. We now wish to report the ligand exchange reaction of bromine in^99mTcBr ₆ ^2– in non-aqueous solvents using 8-hydroxyquinoline (oxine) as the displacing ligand. Analysis of the products obtained by paper chromatography, HPLC and electrophoresis suggest that a 12 Tcoxine complex appears to be the most stable of the complexes formed, probably^99mTc(oxine)₂ Br₂. However, displacement of bromine by polar solvents (both protic and aprotic) can also occur, both on^99mTcBr ₆ ^2– and in the above complex as a consequence of solvolytic reactions. Other Tc-oxine complexes can also be formed upon ligand exchange, but they appear to be stable only under aprotic, non solvolytic conditions. These studies again document that hexahalotechnetate complexes exhibit ligand exchange reactions under non-aqueous conditions, that they allow the ready synthesis of novel technetium complexes, but that because of their high reactivity the effect of competing reactions must be considered.     

Labelling and quality control of cysteine with99mTc and biological distribution

An instant kit of cysteine (amino acid) to be labelled with^99mTc was prepared. Optimal conditions were found, and a procedure to prepare the kit ready to use in liophilized form to gain the highest labelling yield. More than 95% labelling yield was obtained when^99mTc (TcO ₄ ^– ) eluted from^99mTc-generator was added to the contents of the kit. Each kit contains 0.66 mg of SnCl₂·2H₂O as stannite and 66 mg cysteine in lyophilized form. The formulation of cysteine tin (kit) was stable for nearly three months giving labelling yield more than 95%. Using GCS technique, different species of technetium and labelled cysteine were identified when Sephadex (G-50, G-25) was applied. Biodistribution of the labelled preparation revealed that kidney was the target organ. The ratio of accumulated dose in kidneys/liver was greater than 2.     

Methyl ethyl ketone extraction of Tc species

Methyl ethyl ketone extraction of technetium species from aqueous solutions of neutron irradiated ammonium molybdate crystals was studied; the two species extracted were separated by high voltage paper electrophoresis. The one was the^99mTcO ₄ ^– ion and the other, a^99mTc non-charged immobile species, probably TcO₂.aq, which concentrated at the point of application on the electrophoresis paper strip.     

Extraction characteristics of pertechnetate with tetraphenylarsonium in the presence of chloride,nitrate and perchlorate anions

Selected extraction systems of TcO ₄ ^– –(H,Na)A–H₂O/R(TcO₄,A)–CHCl₃, C₆H₅NO₂ type, where A=Cl^–, NO ₃ ^– , ClO ₄ ^– , R=(C₆H₅)₄As⁺, were studied. The solvent extraction of sub- and super-stoichiometric ratio of TcR was performed. The solubility of (C₆H₅)₄AsTcO₄ in water, chloroform and nitrobenzene were determined too. The results of the extractions are presented in the form of TcO ₄ ^– distribution dependencies on the phase composition and the extraction constants of individual TcO ₄ ^– , Cl^–, NO ₃ ^– , ClO ₄ ^– anions and TcO ₄ ^– -Cl^–, TcO ₄ ^– –NO ₃ ^– , TcO ₄ ^– –ClO ₄ ^– ion pairs.     

Using Tc-Re chemical analogy to synthesize and identify new99mTc complexes

The strong chemical resemblance between Tc and Re is applied to design and evaluate experiments with^99mTc complexes. A combination of spectrophotometric and electrophoretic techniques allows to propose the formula [TcO₂/amine/₂]⁺ for compounds prepared by reduction of^99mTcO ₄ ^– with Zn /solid phase/ in presence of several /bidentate/ amines.     

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.     

99mTc-1,7-bis (2-pyridyl)-2,6-diazaheptane (DPTN) complexes: Production yield and stability in slightly basic media

The reduction of^99mTc by SnCl₂ in the presence of 1,7-bis (2-pyridyl)-2,6-diazaheptane (DPTN) has been investigated in borate buffer solutions with pHs ranging from 6.7 to 9.5. The resulting cationic, neutral and anionic complexes, in addition to TcO₂ and TcO ₄ ^– impurities, were separated by high voltage paper electrophoresis. The cationic complex turned into neutral and then into an anionic form via hydrolysis. These three species were also separated by gel filtration on a Bio-Gel P-2 column; their formation yields, stability, and the rate of their hydrolysis are presented as a function of the pH, and the results are discussed.     

A new very sensitive LSC procedure for determination of Tc-99 in environmental samples

A new method for the determination of Tc-99 in different environmental samples has been developed. The sample is carefully ashed in a muffle furnace and then fused with Na₂CO₃ and K₂CO₃. The first step is an enrichment and purification of TcO ₄ ^– on an anion exchange resin. The Tc is desorbed as a cationic thiourea complex, which is held on a cation exchange resin. The complex is destroyed by oxidation to TcO ₄ ^– with (NH₄)₂S₂O₈ in sulfuric acid. From this solution TcO ₄ ^– is extracted into TBP/toluene and the organic phase is mixed with a scintillation cocktail and counted in an anticoincidence shielded LSC. Tc-99m is used as a chemical yield tracer. The decontamination factors for all important fission and activation products and naturally occurring radionuclides are in the range between > 10⁵ and > 10⁸. The detection limit is about 5 mBq per sample at a counting time of 1000 minutes. The maximum sample amount of plants is 500 g dry weight and therefore the lowest detection limit achievable is 10 mBq/kg. Ashing and dissolution of the samples takes 24 h and 4 analyses are performed by one technician in 8 hours. The chemical yield ranges from 50 to 80%.     

Synthesis and biological evaluation of novel 99mTc‐oxo and 99mTc‐tricarbonyl complexes with C3′‐functionalized thymidine dithiocarbamate for tumor imaging

A novel C3′‐functionalized thymidine dithiocarbamate derivative (3’DTC‐TdR) was successfully synthesized and labelled using [^99mTcO]³⁺ core and [^99mTc(CO)₃(H₂O)₃]⁺ core with high yields. The structures of the ^99mTc complexes were verified by preparation and characterization of the corresponding stable rhenium complexes. Both of the complexes were lipophilic and stable in vitro. Cell internalization experiments indicated that the uptakes of ^99mTcO‐3’DTC‐TdR were related to nucleoside transporters. Biodistribution of these complexes in mice bearing tumor showed that they had high tumor uptakes, good tumor/muscle ratios and tumor/blood ratios. Especially for ^99mTcO‐3’DTC‐TdR, it exhibited the highest tumor/muscle ratio and tumor/blood ratio at 4 h post‐injection. SPECT/CT imaging studies indicated clear accumulation in tumor, suggesting ^99mTcO‐3’DTC‐TdR would be a promising candidate for tumor imaging.     

Theoretical study on the electronic spectrum of TcO 4 −

Summary The theoretical electronic spectrum of TcO ₄ ^– calculated by the SAC(symmetry adapted cluster)/SAC-CI method is presented. The spectrum is in good agreement with the experimental one. The observed peaks are assigned and the existence of several absorptions in the energy region higher than that observed is predicted. The difference and the similarity between the electronic spectra of TcO ₄ ^– and MnO ₄ ^– are clarified. The spectral difference between TcO ₄ ^– and MnO ₄ ^– is due to a remarkably high energy shift of the 3¹T₂ state of TcO ₄ ^– .     

Effect of chemical condition of technetium-99m sodium pertechnetate on the active kit components and radiolabeling yield of Tru-Scint® ADTM monoclonal antibody kit

The chemical condition of^99mTc eluate obtained from a⁹⁹Mo-^99mTc generator is a function of the source, time elapsed after elution and age of the eluate. The radiochemical purity and stability of^99mTc labeled MAb-170 (Tru-Scint^®AD^TM, photoactivated monoclonal antibody kit) preparations was evaluated comparing pertechnetate source of known age and elution history. The effect of H₂O₂, a radiolytic impurity in^99mTc eluates, on the active kit components stannous ion and photoactivated MAb and radiolabeling, yield has been investigated. The lyophilized Tru-Scint^® AD^TM kit has been labeled with 20 to 80 mCi in 0.5 to 4.0 ml of Sodium Pertechnetate^99mTc Injection, USP. The eluates were obtained from three brands of generators and used up to six hours after elution. The kits were reconstituted either with Sodium Pertechnetate^99mTc Injection, USP or Sodium Chloride Injection, USP, 0.9% containing known amounts of H₂O₂. The reconstituted kits were analyzed for radiolabeling yield and radiochemical impurities, stannous ion and protein sulfhydryl group. The results indicated that the radiolabeling yield is a function of both the chemical condition of^99mTc eluate, generator brand and the radiolabeling parameters like reconstitution volume and activity. The observed radiolabeling yield differences did not depend on the amount of chemical technetium in the eluate. The major radiochemical impurities at 15-minute post labeling have been identified as the^99mTc-buffer complex and column adsorbed reduced^99mTc (^99mTc-Ad) species and not the unreduced^99mTcO ₄ ^– .     

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.     

Determination of technetium-99 in environmental samples by solvent extraction at controlled valence

Distribution coefficients of technetium and ruthenium are determined under different conditions with CCl₄, cyclohexanone, and 5% tri-isooctylamine (TIOA)/xylene. A method for analyzing⁹⁹Tc in environmental samples has been developed by solvent extraction in which the valences of technetium and ruthenium are controlled with H₂O₂ and NaClO. Technetium and ruthenium which are oxidized to TcO ₄ ^– and RuO ₄ ^– by NaClO are separated by extraction with CCl₄ at pH 4. The RuO ₄ ^– is reduced to low valence and technetium is kept in the TcO ₄ ^– state with H₂O₂. Technetium, ruthenium, and other nuclides are subsequently separated by solvent extraction with cyclohexanone and 5% TIOA/xylene. The decontamination of the procedure is 1.35·10⁵ for¹⁰³Ru and 1.66·10⁵ for^110mAg. The chemical yield of technetium-99 is 55%.On leave from Institute of Atomic Energy, Beijing, China