Determination of99Tc-DPD complex composition and valence states of technetium

DPD (2,3-dicarboxypropane-1,1-diphosphonic acid) forms two complexes with⁹⁹Tc, previously reduced by Sn(II): with _max at 410 nm (pH 3–7), and at 515 nm (pH 5–9.6). By Job's method, formation of complexes with DPD:Tc molar ratios of 21 and 23 was found in acidic medium (pH=3). In order to determine the valence states of Tc in the complex, taking into account that formation of⁹⁹Tc-DPD complex does not occur in absence of a reducing agent (here divalent tin), the redox potentiometric titration method was applied. In acidic medium (pH=3), Tc was reduced to Tc(III) by Sn(II), while in presence of DPD to Tc(IV). In strongly alkaline medium (pH>13) the situation was reverse: Tc(III) was formed in the DPD complex, while Tc(IV) in absence of the ligand. In slightly alkaline medium (pH about 8) in both cases (with or without the ligand) TC(III) was obtained at the titration end point. This phenomenon can explain the dependence of^99mTc-radiopharmaceutical complexes on the sequence of reagent addition. These conclusions are very important for^99mTc-DPD radiopharmaceutical solutions used in diagnostic nuclear medicine for skeletal imaging.     

Effect of cuprous ion on labeling of three skeletal imaging agents with99mTc

The effect of increased content of copper on the radiochemical composition of three skeletal imaging agents:^99mTc(Sn)-methylene diphosphonate (MDP),^99mTc(Sn)-pyrophosphate (PYP) and^99mTc(Sn)-2,3-dicarboxypropane-1, 1-diphosphonate (DPD) was observed only in the case of^99mTc(Sn)-MDP. It was found that the radiochemical purity of this radiopharmaceutical falls to about 50% when the copper content reaches about 10^–5 mol dm^–3. According to the results of radiochemical and biological analyses, it could be concluded that with the increase of copper content, the content of free pertechnetate rises, too. The two other radiopharmaceuticals,^99mTc(Sn)-PYP and^99mTc(Sn)-DPD, were found to be stable under the given experimental conditions.     

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.     

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.     

Comparative quality control of some bone-seeking99mTc radiopharmaceuticals by gel chromatography

The radiochemical purity of the three osteopatic ligands:^99mTc(Sn)-PyP,^99mTc(Sn)-DPD and^99mTc(Sn)-MDP has been determined by gel chromatography on Sephadex. The results of the analyses strongly depend on the composition of the eluent. The dilution effect of pure saline as eluent was observed in all the preparations examined. The most sensitive was found to be^99mTc(Sn)-PyP. The retention of^99mTc activity bound to the gel matrix (^99mTc-hydrolyte) was over 30%. The diphosphonates were found to be more stable (retention 10–15%). The retention is substantially lower, i.e. a high recovery of the labeled complexes is obtained when the eluent contains the ligand. The best results are obtained when the eluent contains the same concentrations of ligand and reductant as in the labeled complex. There was no significant difference in the behavior of the given radiopharmaceuticals prepared as a fresh solution and in the freeze-dried kit.     

The Complexes of Holmium with Methylenediphosphonate and 1-Hydroxyethylidenephosphonate

The composition and stability of holmium methylenediphosphonate (MDP) and 1-hydroxyethylidenephosphonate (HEDP) complexes were studied by potentiometric titration methods in 0.1M NaCl at 25 °C. It was found that besides L^4– anions the protonated H _n L^(4–n)– species (n = 1–3 for MDP and n = 1–4 for HEDP) are present in the pH region 3 to 10. The presence of the undissociated acids (H₄L) has not been unambiguously proved for MDP. The complexes of the composition HoH _n L (n varies from 1 to –2 for MDP and from 1 to –1 for HEDP) have been found if the concentration of the ligand is higher than the concentration of holmium. The protonation constants of both acids and the stability constants of the complexes discussed were determined and the comparison with literature data of analogical complexes of other lanthanides was performed.     

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.     

Kinetics of the radiation chemical reactions of tervalent and quadrivalent actinides and lanthanides in carbonate solutions

The reactions of the ions of tervalent and quadrivalent actinides and lanthanides with hydrated electrons e_aq ^– and CO₃ ^– radicals in concentrated carbonate solutions have been studied by microsecond pulse radiolysis, using spectrophotometric recording of short-lived particles. It is shown that the rate of the reactions of e_aq ^– with carbonato complexes of Ce(IV), Pu(IV), and Np(IV) is controlled by diffusion. The carbonato complex of Eu(III) reacts with e_aq ^–appreciably more slowly. A linear relationship is obtained between the logarithm of the rate constant for the reactions of CO₃ ^– with the carbonato complexes of Am(III), Ce(III), and Pu(III) and the redox potential of the complexes. The rate of the reaction of CO₃ ^– with Np(III) in carbonate solutions is controlled by diffusion.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 28–32, January, 1990.     

Determination of complex forming conditions of 8-hydroxyquinoline with technetium-99m

Complex forming conditions of 8-hydroxyquinoline with^99mTc have been specified.^99mTcO₄ ^– has been reduced by SnCl₂ to a lower oxidation level. Labeling yields have been determined by ITLC (Instant Thin Layer Chromatography). Various parameters, such as pH, temperature, reaction time, ligand to SnCl₂ ratio, which can affect the labeling yields, have been determined. Optimum conditions are 4–7 for pH; 15–20°C (room) for temperature; 1.55 for ligand to SnCl₂ ratio and 5 min for reaction time.     

99mTc-labelled compounds prepared with tungsten(III) as the reducing agent

The application of K₃W₂Cl₉ as reducing agent in preparation of^99mTc-labelled compounds is described. Pertechnetate reduction was carried out in solutions of pH 2 and also of pH 5.5. DTPA, citrate, gluconate, HEDSPA and MDP were successfully labelled. Two types of labelled gluconate complexes were obtained. Complex I exhibited in rats an increased^99mTc affinity to kidneys (21%). Complex II exhibited an increased^99mTc affinity to bone (8.7%). Two types of labelled HEDSPA preparations were obtained: one yielded 29%^99mTc activity in bone, the other type exhibited only 13.4%. The results indicated the absence of mixed complexes.     

Adsorption properties of charcoal impregnated with stannic chloride

Adsorption behaviour of the individual tracer ions:¹³⁴Cs(I),^85,89Sr(II),^131,133Ba (II),⁹⁰Y(III),¹⁴¹Ce(III),^152,154Eu(III),⁹⁵Zr(IV),^175,181Hf(IV),⁹⁵Nb(V),⁶⁰Co(II),¹¹⁵Cd(II),^99mTc(VII), and¹³¹I(-I) on charcoal impregnated with stannic chloride from Hcl solutions, was investigated. Batch equilibrium distribution coefficients of the respective ions indicated strong anion exchange properties towards impregnated charcoal. The column breakthrough sorption capacity was of the order of 0.62–0.66 meq·g^–1 of dry adsorbent. Small chromatographic columns of impregnated charcoal could achieve rapid and quantitative separation procedures in HCl medium. Strongly adsorbed anions such as TcO ₄ ^– and I^– ions could be eluted with NH₄SCN and NH₄NO₂ eluents, respectively.     

Sorption of Tc(IV) and Tc(VII) on Soils: Influence of Humic Substances

The technetium sorption behaviour in different samples of soils was studied under aerobic conditions. Tc(VII) was reduced to Tc(IV) by Sn²⁺ ions. About 99% of reduced technetium is absorbed by the soils under investigation. Sorption of TcO₄ ^– was studied in short-term (1-hour) and long-term (1-month) experiments. Sorption of TcO₄ ^– in presence of sodium humate (Aldrich) was generally lower than from pure water (from 99% to 12%) and depends on the depth of origin of the ground. Immobilisation of TcO₄ ^– after sorption on superficial sample of soils was studied by paper chromatography. Oxidation of Tc(IV) in presence of NO₃ ^– and NO₂ ^– (concentration range 10^–1–10^–5 mol·dm^–3) ions was studied as a function of time and concentration of NO₃ ^– and NO₂ ^– ions. The content of Tc(IV) in NO₃ ^– and NO₂ ^– solutions decreases with time (46 hours) relatively slowly.     

Photolysis of titanium (III) complexes in alcoholic matrices at 77‡k

Using the electron spectroscopy and EPR methods, it was found that during UV irradiation of frozen alcoholic solutions of distorted octahedral complexes [Ti(ROH)₄Cl₂]⁺ and [Ti(ROH)₆]³⁺, distorted tetrahedral hydroxide complexes of titanium (III) are obtained. The mechanism of the process, including successive redox reactions of the titanium compounds has been discussed. As the result of a phototransfer of an electron from the central atom orbitals to the vacant orbitals of the ligands (alcohol molecules) a titanium (IV) compound is obtained containing an anion radical of the alcohol as the ligand. The compound is unstable and undergoes ultraspheric transformations. Rupture of the C-O bond occurs in the anionradical of the alcohol; ethyl radicals and hydroxide complexes of titanium (IV) are thus formed, which by the action of light quanta transform into hydroxide complexes of titanium (III).Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 21, No. 4, pp. 480–484, July–August, 1985.     

The feasibility of producing a99Mo:99mTc generator using the Miniature Neutron Source Reactor (MNSR)

A theoretical investigation of the feasibility of producing a molybdenum-99: technetium-99m generator from MoO₃ using a 30 kW Miniature Neutron Source Reactor (MNSR) has been made. At the rated thermal neutron flux of 10¹² n·cm^–2·s^–1 and irradiation time of 2.5 hours per day, for 8 consecutive days, activities of 7.1 mCi and 5.2 mCi were calculated for⁹⁹Mo and^99mTc, respectively. A 20 g sample of 99.5% chemically pure MoO₃ was used. The advantage for operating the reactor for 8 days instead of 6 days would be an increase of 11.4% and 15.5%, respectively, in the amount of⁹⁹Mo and^99mTc produced. it is calculated that an optimum irradiation scheme is achieved when the reactor is operated for an extended period of 5 hours a day for 5 days a week at a lower flux level of 7.5·10¹¹ n·cm^–2·s^–1. With this optimum operation scheme, there would be an increase in the weekly specific activity of 36% and 37.9% for⁹⁹Mo and^99mTc, respectively.     

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.     

Distribution and behaviour of99Tc,237Np,239,240Pu,and241Am in the coastal and estuarine sediments of the Irish Sea

Intertidal coastal and estuarine sediments from 24 sites in the Irish Sea have been analyzed for⁹⁹Tc,²³⁷Np,²³⁸Pu,^239,240Pu and²⁴¹Am. The²³⁷Np activity and²³⁹Pu/²⁴⁰Pu ratio were measured simultaneously by ICP-MS, and⁹⁹Tc was determined by HR-ICP-MS which is ten times more sensitive than Q-ICP-MS.The activities of⁹⁹Tc,²³⁷Np,^239,240Pu and²⁴¹Am were distributed over a wide range of 1.5–70.5, 0.01–13.3, 2.3–1589, 2.6–1894 Bq/kg, respectively. Activities of these radionuclides decreased exponentially with distance from the Sellafield source. The²⁴¹Am/^239,240Pu and²³⁷Np/^239,240Pu ratios were almost constant with distance from the Sellafield. This result suggests that the distribution and behavior of Np and Pu are controlled by complicated factors such as the influence of transport, the variation with time of Np/Pu ratio in the Sellafield discharges and sedimentary mixing processes in the Irish Sea.     

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.     

Reaction of [TcNCl4]− with ethylenediamine-N,N'-diacetic acid ligand

The reaction of [^99mTcNCl₄]^– with ethylenediamine-N,N'-diacetic acid (ENDA) has been studied. Starting from [^99mTcNCl₄]^– prepared according to the method of Apparu et al.6, the exchange reaction with ENDA in the presence of stannous tartrate led to the formation of an anionic^99mTcN-ENDA complex. The labeling yield was about 90% at pH values of 10.5 and 6.5. In the absence of the reducing agent the formation of^99mTcO₄ ^– is reflected in the decrease of the complex yield. The exchange reaction of [⁹⁹TcNCl₄]^– with ENDA at pH 6.5 and in the absence of a reducing agent resulted in the formation of the anionic⁹⁹TcN-ENDA complex and⁹⁹TcO₄ ^–. The spectrophotometric characteristics (UV-vis. and IR) of the pure complex are similar to those of some tcN²⁺-complexes with amine ligands. The electrophoretic and chromatographic behaviors of^99mTcN- and⁹⁹TcN-ENDA anions are identical; this proves the formation of the same complex with both radionuclides.     

Studies on intermolecular interactions of metal chelate complexes. Part X. Interactions of metal chelates with ozone

Summary The interactions of more than forty metal chelate complexes, dithiocarbamates, dithiophosphates and acetylacetonates, with ozone are studied in homogeneous phase and the stoichiometry and the rate constants of the reactions estimated. Most powerful ozone deactivators are nickel(II) and copper(II) dithiocarbamate and dithiophosphate complexes interacting with 6.5 moles ozone per mole of the ligand with rate constant >0⁶m · I^–1 · s^–1. The remote ligand substituents do not influence the reaction parameters. Other sulphur-containing complexes of iron(III), cobalt(II), cobalt(III), zinc(II), manganese(III), bismuth(III), antimony(III), arsenic(III), cadmium(II), platinum(II), palladium(II) and chromium(III) deactivate 3–4 moles ozone per mole ligand with rate constants of 10²–10⁴ m · I^–1 · s^–1. Acetylacetonate complexes of copper(II), nickel(II), cobalt(III), iron(III), chromium (III), and oxovanadium(II) deactivate 1–3 moles ozone per mole ligand with a rate constant of 10–10⁴ m · I^–1 · s^–1. Using e.p.r. and electronic spectra, some intermediate products are detected and the mechanism of the reaction is discussed. The reported data are compared with other widely used antiozonants and the metal chelates are shown to have several advantages.     

Characteristic features of decomposition of potassium pentacyano-cobaltates(III) on a bombardment with fast atoms

Mass spectra were obtained of cobalt(III) pentacyanide complexes of the K_n[Co(CN)₅X] type bombarded by fast atoms, where X = H₂O, NO₂ ^–, NO^–. The ligand elimination processes from the coordination sphere of the pentacyanides and the redox reactions of the complexes were studied.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 28, No. 2, pp. 173–176, March–April, 1992.