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.     

Characteristics and behavior of a99Mo/99mTc generator using irradiated titanium molybdate as column matrix

A⁹⁹Mo/^99mTc generator, system was made with a performed titanium molybdate gel. The irradiation was carried out at a medium neutron flux of 1.5×10¹³ n cm^–2·s^–1. The irradiated matrix was loaded on top of a column composed of hydrous zirconium oxide alumina. The elution efficiency and the amount of total technetium per mCi^99mTc in the generator eluents have been determined. Molybdenum breakthrough has also been determined and compared with literature values. The influence of the particle size, water content, neutron flux and molybdenum content on the total^99mTc-activity has been investigated.     

A99Mo-99mTc generator based on the use of zirconium molybdophosphate-99Mo gel

A modified⁹⁹Mo–^99mTc gel generator is described. The present generator uses an insoluble zirconium molybdophosphate (ZrMP) gel tagged with⁹⁹Mo. Molybdenum-99 is chemically combined in the gel structure and cannot be eluted from the matrix. The presence of phosphate increases the chemical stability of the gel and decreases the molybdenum breakthrough. The prepared gel is sufficiently porous to permit ready diffusion of^99mTcO ₄ ^– which can be cluted with saline in yields of up to 90%. The gel was found to contain 25.1% Mo, 21.9% Zr, and 0.7% P in a molar ratio of 1.09:1.0:0.09, respectively. The high molybdenum content of the gel allows the use of cheap, non-polluting (n, )⁹⁹Mo. The eluted^99mTc was of high purity and can be used for medical and pharmaceutical applications.     

Methods and results of99Tc analysis of Nevada test site groundwaters

Samples of the long-lived fission product⁹⁹Tc were isolated from liter quantities of selected groundwaters from the Cheshire, Bilby, Nash, Bourbon, Cambric and Faultless event sites and the⁹⁹Tc concentrations determined by liquid scintillation counting. Although⁹⁹Tc was detected in several of the samples, the concentrations did not exceed the MPC_w of 3·10^–4 Ci/ml and the results indicated that the Tc was present primarily in solution rather than sorbed on colloidal-size material.     

Determination of99Tc in coastal seawater collected in Fukuoka,Japan

Concentrations of⁹⁹Tc were determined by inductively coupled plasma mass spectrometry (ICP-MS) on coastal seawater in the general environment in Japan. Technetium was enriched on iron hydroxide by repetitive co-precipitation method from a large volume of seawater and separated from impurities by solvent extraction and ion-exchange techniques. The concentrations of⁹⁹Tc were 1.0 to 7.4 Bq1^–1, which was one order of magnitude lower than the level reported on seawater from general environment by beta-ray counting. Concentrations of¹³⁷Cs determined on the same seawater were 3.7 and 3.9 mBq1^–1. The activity ratio of⁹⁹Tc/¹³⁷Cs was calculated to be 2.7×10^–4. This ratio was very close to the value expected for fallout from nuclear tests.     

Preparation of 99Mo/99mTc generator based on alumina 99Mo-molybdate (VI) gel

In this work alumina ⁹⁹Mo-molybdate (VI) gel is evaluated as a column matrix for use in the preparation of small chromatographic column type ^99mTc generator. Alumina molybdate (VI) gel is prepared by dissolving inactive MoO₃ with aluminum foil in 5 M NaOH solution containing ⁹⁹Mo radiotracer. After complete dissolution, 0.5 H₂O₂ was added to the reaction mixture solution and acidified to pH 5.5 with concentrated HNO₃. The formed AlMo precipitate was washed with NaNO₃ solution, dried at 50 °C for 24 h and then packed in the form of a chromatographic column for elution of the generated ^99mTc radionuclide with physiological saline solution (0.9 % NaCl). Greater than 86 % of the generated ^99mTc activity is immediately and reproducibly eluted with passing 10 mL of the saline solution through 2.0 g of alumina ⁹⁹Mo-molybdate column bed at a flow rate of about 1.0 mL/min. The high radiochemical ≥98.6 % TcO₄ ^?, radionuclidic ≥99.90 % ^99mTc and chemical purities of the eluates satisfy the specifications for use in nuclear medicine.     

Technetium-99m generators based on neutron irradiated 12-molybdocerate as column matrix

Neutron irradiated 12-molybdocerate(IV) is evaluated as a column matrix for use in preparation of small chromatographic column type^99mTc generators. Greater than 87% of the generated^99mTc activity is immediately and reproducibly eluted with passing 10 cm³ of saline or chromated saline solutions through 3.0 g of molybdocerate column bed at flow rates of about 1.0 cm³/min. The elution performance of^99mTc does not drastically change with increasing the drying temperature and/or the particles sixe of the column matrix in the range investigated. Saline eluent containing 5·10^–5M CrO ₄ ^2– increases the radiochemical purity of the eluate to >98% TcO ₄ ^– . Radionuclidic and chemical purities of the eluates satisfy the specifications for use in nuclear medicine.     

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.     

Extraction of99mTc into MEK from large quantity of molybdate retained on alumina column

A column-extraction generator based on the adsorption of alkaline sodium molybdate on an acid alumina column is described. Generators containing 1 to 3.2 g of molybdenum /⁹⁹Mo/ absorbed on 12–15 g of acid alumina, with activities ranging from 0.52 to 5.2 GBq /14 to 140 mCi/, have been prepared and evaluated. The results indicate that^99mTc can be quantitatively eluted from such columns with about 10 ml of MEK. The yields were found to be in the range of 70 to 90% over 3–6 days.     

Rapid determination of 99Tc in environmental samples by high resolution ICP-MS coupled with on-line flow injection system

High resolution inductively coupled plasma mass spectrometry coupled with an on-line flow injection system (FI-HR-ICP-MS) was applied to determine the ultra-trace level ⁹⁹Tc in soil. The flow injection system (PrepLab) was composed of two TEVA-Spec^Òresins, reduced remarkably the sample amounts and the analysis time, compared to the conventional analytical methods. In the flow injection system, Mo and Ru were sufficiently eliminated by using the flow injection system, with the decontamination factors of 1.6^.10⁴ and 9.9^.10⁵, respectively. With the present method, it was possible to determine ultra-low level of ⁹⁹Tc in 3-6 g soil at 3–5 hours of analysis time per sample. The relative standard deviation for each sample was less than 4%. The detection limits for ⁹⁹Tc was 85 fg^.ml^–1 (0.05 mBq^.ml^–1), which was calculated from the three times standard deviation of the count rate of the blank.     

Evaluation of fresh and old eluate of <Superscript>99</Superscript>Mo/<Superscript>99m</Superscript>Tc generators used for labeling of different pharmaceutical kits

Summary Sixty ⁹⁹Mo/^99mTc wet column generators, loaded with two different ⁹⁹Mo activities, were analyzed in order to assess the quality of their eluates. Each elution was used for labeling of different radiopharmaceuticals, in order to evaluate whether “risky” elutions, namely those performed just after generator delivery and at 72 hours or more from the last elution, could be conveniently employed when fresh available radioactivity is not enough for the planned labeling or when shipping problems arise, or delay in delivery of a new generator occurs. Radiochemical quality control of all radiopharmaceuticals labeled with these elutions was performed. The elutions differed mainly in ⁹⁹Tc ground state (^99gTc) and amounts of oxidizing impurities. Radiolabeling procedures, however, were not affected, suggesting that these “risky” elutions might be appropriately used, in “emergency” conditions, for labeling radiopharmaceuticals although their radiochemical purity control is recommended prior to patient administration.     

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.     

Separation of rare earth elements from uranium by solvent extraction and ion exchange

The detection limit of⁹⁹Tc in (,) radio-activation analysis was determined in the presence of molybdenum and compared with that of⁹⁹Tc in pure materials in the previous paper. The isotopic ratio of molybdenum in a⁹⁹Mo–^99mTc generator column could be simultaneously determined by photon activation analysis.     

Distribution of gamma radionuclidic impurities in routine99mTc generator eluates

Fission-produced -emitting radionuclidic impurities in eluates obtained by elution of routine (n,f)⁹⁹Mo/^99mTc generators have been determined. Four radionuclidic impurities were identified and quantitatively measured by the method of -spectrometry. The distribution of¹⁰³Ru,¹⁰⁶Ru,¹²⁵Sb and¹³¹I in the eluates was followed. The fraction of the activity which has been desorbed from alumina in the generator column during the lifetime of the generator was determined for earch radionuclide found. The contents of radionuclidic impurities in the eluates were compared with the criteria of radionuclidic purity prescribed by the Pharmacopoeia.     

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 generator based on 12-molybdocerate —99Mo precipitate as column matrix

The preparation of insoluble 12-molybdocerate(IV) from⁹⁹Mo of low specific activity, produced by thermal neutron irradiation of MoO₃, is described. Samples of the material are dried at 50, 100 and 200°C and used as column matrices from which the generated^99mTc activity is periodically eluted with saline solution or saline solution containing 5·10^–5M K₂CrO₄ as an oxidant. The elution yields of^99mTc are high and reproducible (95–81%) with radionuclidic purity 99.98%. Both chemical and radiochemical purity (as TcO ₄ ^– ) of the eluates decrease with increasing drying temperature of the column matrix. Using chromated saline solution as eluent improves the radiochemical purity of the^99mTc eluate.     

<Superscript>99</Superscript>Mo/<Superscript>99m</Superscript>Tc generators based on aluminum molybdate gel matrix prepared by nano method

A procedure for preparation of ⁹⁹Mo/^99mTc radioisotope generator based on low specific activity neutron activated ⁹⁹Mo was developed. Aluminum molybdate(VI)-⁹⁹Mo of high Mo(VI) content (~?364 mg/g Al⁹⁹Mo) was prepared by mixing low specific activity molybdate(VI)-⁹⁹Mo and aluminum mixture solution with isoamyl alcohol. Al⁹⁹Mo gel matrix was precipitated when the pH of the mixture solution was raised to ~?5 by addition of NaOH to the mixture. Radiometric measurements indicate the strong fixation of Molybdate(VI)-⁹⁹Mo species in the form of the sparingly insoluble Al⁹⁹Mo gel matrix. The prepared AlMo gel matrix was physiochemically characterized. Al⁹⁹Mo gel matrix was used as a base material for preparation of ⁹⁹Mo/^99mTc generator. The ^99mTc eluted from ⁹⁹Mo/^99mTc radioisotope generator was found to have relatively high elution yield (84?±?2.3%), radionuclidic (≥?99.99%), radiochemical (98.1?±?0.9%) and chemical purity.     

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.     

Evaluation of proton induced reactions on 100Mo: New cross sections for production of 99 mTc and 99Mo

The use of the ⁹⁹Mo^99mTc generator in nuclear medicine is well established world wide. The production of the ⁹⁹Mo (T_1/2 = 66 h) parent as a fission product of ²³⁵U is largely based on the use of reactor technology. From the early 1990's accelerator based production methods to provide either direct produced ^99mTc or the parent ⁹⁹Mo, were studied and suggested as potential alternatives to the reactor based production of ⁹⁹Mo. A possible pathway for the charged particle production of ^99mTc and ⁹⁹Mo is irradiation of molybdenum metal with protons via the reaction ¹⁰⁰Mo(p,2n)^99mTc and ¹⁰⁰Mo(p,pn)⁹⁹Mo, respectively. The earlier published excitation functions show large differences in their maximum that result in large differences in the calculated yields. We therefore decided to study the excitation function for these proton-induced reactions. In this work the newly measured excitation functions as well as an evaluation of earlier measured data and a discussion of the observed disagreements are presented.     

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.