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.     

A novel technique for the separation of99mTc from99Mo

A new technique for the separation of^99mTc from low specific activity⁹⁹Mo is reported. A separation based on the principle of precipitation of⁹⁹Mo as calcium molybdate has been investigated. On precipitating⁹⁹MoO ₄ ^2– from alkaline solution as calcium molybdate under controlled conditions, the^99mTcO ₄ ^– is found to remain quantitatively in the supernatant solution with little carry-over of⁹⁹Mo. This calcium molybdate (⁹⁹Mo) could be redissolved and reprecipitated at regular intervals, yielding^99mTc quantitatively in aqueous neutral solutions. Calcium molybdate precipitates containing up to 1.5 GBq of⁹⁹Mo and 130–180 mg of molybdenum were prepared and evaluated. The performance in terms of repeated^99mTc separation gave yields of 75–93% with acceptable readionuclidic and radiochemical purity.     

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.     

Hydrated titanium dioxide as an adsorbent for99Mo−99mTc generator

The adsorption behaviour of⁹⁹Mo in the form of molybdate and of^99mTc in the form of pertechnetate on hydrated titanium dioxide was investigated at different molarities of hydrochloric acid. The adsorption capacity of molybdate on hydrated TiO₂ is higher than on Al₂O₃. A^99mTc-generator is suggested. This generator is based on the adsorption of (⁹⁹Mo) molybdate on hydrated TiO₂, at acidities of 0.05–0.1M. HCl.^99mTc is eluted with 0.9% NaCl. Radionuclidic, radiochemical and chemical purities of the eluates were checked. This generator seems to have a great potential as compared to the traditional alumina generators.     

<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.     

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.     

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.     

Solid targets for 99mTc production on medical cyclotrons

Recent disruptions in the molybdenum-technetium generator supply chain prompted a review of non-reactor based production methods for both ⁹⁹Mo and ^99mTc. Small medical cyclotrons (E _p ~ 16–24 MeV) are capable of producing Curie quantities of ^99mTc from isotopically enriched ¹⁰⁰Mo using the ¹⁰⁰Mo(p,2n)^99mTc reaction. Unlike most other metallic target materials for routine production of medical radioisotopes, molybdenum cannot be deposited by reductive electroplating from aqueous salt solutions. To overcome this issue, we developed a new process for solid molybdenum targets based on the electrophoretic deposition of fine ¹⁰⁰Mo powder onto a tantalum plate, followed by high temperature sintering. The targets obtained were mechanically robust and thermally stable when irradiated with protons at high power density.     

Developing a Chromatographic 99mTc Generator Based on Mesoporous Alumina for Industrial Radiotracer Applications: A Potential New Generation Sorbent for Using Low-Specific-Activity 99Mo

The commercial low-pressure column chromatographic ⁹⁹Mo/^99mTc generator represents a reliable source of onsite, ready-to-use ^99mTc for industrial applications. These generators use fission-produced ⁹⁹Mo of high specific activity, posing serious production challenges and raising proliferation concerns. Therefore, many concepts are aimed at using low-specific-activity (LSA) ⁹⁹Mo. Nonetheless, the main roadblock is the low sorption capacity of the used alumina (Al₂O₃). This study investigates the feasibility of using commercial alumina incorporated with LSA ⁹⁹Mo to develop a useful ⁹⁹Mo/^99mTc generator for industrial radiotracer applications. First, the adsorption profiles of some commercial alumina sorbents for LSA ⁹⁹Mo were tested under different experimental conditions. Then, the potential materials to develop a ⁹⁹Mo/^99mTc generator were selected and evaluated regarding elution yield of ^99mTc and purity. Among the sorbents investigated in this study, mesoporous alumina (SA-517747) presented a unique sorption-elution profile. It demonstrated a high equilibrium and dynamic sorption capacity of 148 ± 8 and 108 ± 6 mg Mo/g. Furthermore, ^99mTc was eluted with high yield and adequate chemical, radiochemical, and radionuclidic purity. Therefore, this approach provides an efficient and cost-effective way to supply onsite ^99mTc for radiotracer applications independent of fission-produced ⁹⁹Mo technology.     

The quality of99mTc eluates

The possible effects of several protecting procedures on the quality of^99mTc eluates were investigated. The content of⁹⁹Mo in the eluates (⁹⁹Mo breakthrough) was expressed in (%) with respect to the total adsorbed⁹⁹Mo radioactivity and in () i.e. as the ratio of⁹⁹Mo and^99mTc radioactivities in each particular eluate. The radiochemical purity was expressed in (%) of^99mTc(VII) in the eluates. The content of Al³⁺ and Cu²⁺ as chemical impurities was also determined.     

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.     

Determination of technetium in99Mo/99m Tc-generators

The Tc budget in several ROTOP-generators was determined by neutron activation analysis (NAA) and UV-spectroscopy. The complete procedure included the preparation of the generator, elution cycle in 24 to 72 h intervals and evaporation of the eluates to dryness. The samples were aliquoted, irradiated in the reactor and analyzed via⁹⁹Tc(n, n')^99mTc⁹⁹Tc reaction as well as by UV-absorption due to pertechnetate. The most reliable method proved to be NAA including chemical separation from²⁴Na by ion exchange after the complete decay of³⁸Cl. The detection limit was 50 ppb (3 ng Tc), compared with the total amount of several 10^–5 g down to 10^–7 g Tc in the system and its fractions. The mass balance and the elution profiles obtained correspond very well to the theoretical values. The results permit further quantitative considerations on both elution kinetics and the generator system.     

Desorption of99Mo from spent99Mo/99mTc generator

A simple method for desorption and purification of⁹⁹Mo from spent⁹⁹Mo/^99mTc generators is described. The alumina column was washed successively with 0.9% saline water, 35% H₂O₂, and then the⁹⁹Mo was eluted with 2M NH₄OH. Ammonia and residual H₂O₂ were removed by heating the eluate. Finally,⁹⁹Mo solution was passed through a 0.2 m membrane filter to remove precipitated aluminium hydroxide.     

Precision measurements of the half-lives of60mCo,79mSe,104mRh,149Nd,176mLu,177Lu and198Au

Carrier-free^99mTcO₄ ^– eluated from clinical⁹⁹Mo/^99mTc generators was examined to determine its specific activity. The observed specific activity was found to be always lower than the calculated value based on the⁹⁹Mo–^99mTc–⁹⁹Tc decay scheme data. These results could be explained in terms of existence of excess Tc loaded onto generator column.     

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.     

Practicality of Tetragonal Nano-Zirconia as a Prospective Sorbent in the Preparation of 99Mo/99mTc Generator for Biomedical Applications

The feasibility of using tetragonal nano-zirconia (t-ZrO₂) as an effective sorbent for developing a ⁹⁹Mo/^99mTc chromatographic generator was demonstrated. The structural characteristics of the sorbent matrix were investigated by different analytical techniques such as XRD, BET surface area analysis, FT-IR, TEM etc. The material synthesized was nanocrystalline, in tetragonal phase with an average particle size of ~7 nm and a large surface area of 340 m² g^?1. The equilibrium sorption capacity of t-ZrO₂ is >250 mg Mo g^?1. The present study indicates that ⁹⁹Mo is both strongly and selectively retained by t-ZrO₂ at acidic pH and ^99mTc could be readily eluted from it, using 0.9% NaCl solution. A 9.25 GBq (250 mCi) t-ZrO₂ based chromatographic ⁹⁹Mo/^99mTc generator was developed and its performance was repeatedly evaluated for 10 days. ^99mTc could be eluted with >85% yield having acceptable radionuclidic, radiochemical and chemical purity for clinical applications. The compatibility of the product in the preparation of ^99mTc labeled formulations such as ^99mTc-EC and ^99mTc-DMSA was evaluated and found to be satisfactory.     

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 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 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.