An Alumina Based 99Mo–99mTc Generator to Produce 99mTc in Organic Medium Suitable for Industrial Radiotracer Applications

An industrial chromatographic ⁹⁹Mo–^99mTc generator has been developed with the aid of chromatographic alumina to obtain ^99mTc in a non-aqueous medium. This generator system takes advantage of tributyl phosphate to extract ^99mTc selectively with appreciable yield and in high radiochemical and radionuclidic purity. This facile, versatile and efficient approach provides ^99mTc at industrial sites in a medium soluble in hydrocarbon solvents, for radiotracer applications.     

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.     

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.     

Contributions to the coordination chemistry of technetium

The radionuclide^99mTc is widely used in nuclear medical diagnostics. Radiopharmaceuticals containing coordination compounds labeled with^99mTc⁴⁺ or^99mTc⁵⁺ can be rapidly prepared from pertechnetate eluted from a⁹⁹Mo/^99mTc generator. For the optimization of the imaging agent it is essential to determine the exact chemical structure of the Tc complex. This can be achieved by synthesizing macroscopic amounts of the analogous long-lived^99gTc compound and by its analysis by appropriate spectroscopy methods. We have successfully synthesized and characterized new technetium complexes with amino acids and also with ligands containing nitrogen, oxygen and sulfur atoms.     

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.     

<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.     

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 ^– .     

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.     

Separation of99mTc from parent99Mo by solid-phase column extraction as a simple option for a new99mTc generator concept

Evidence is obtained to show that the liquidliquid extraction separation of^99mTc from⁹⁹Mo with methyl ethyl ketone, methyl propyl ketone and methyl isobutyl ketone can be transformed into a solid-phase column extraction procedure. The aqueous alkaline⁹⁹molybdate solution is immobilized on a column of a granular large-pore diatomaceous earch support, which is the neluted with the abovementioned extractants. Rapid and clean separation of^99mTc can be with all three solvents. The^99mTc can be back-extracted from the organic phase on a column filled with distilled water /or saline/ loaded granular diatomaceous earth /Extrelut^®/. The possibility of using the abovementioned procedure as a basis for a new^99mTc/⁹⁹Mo generator concept is envisaged.     

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.     

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.     

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.     

Application possibilities of a new generator concept for99mTc production by means of the Triga-Mark III reactor in Mexico

A new concept of prefabricated^99mTc generator has been experimentally tested as a possible procedure for local production of^99mTc for medical purposes by means of the ININ-Salazar /Mexico/ Triga-Mark III reactor working at 1 MW.Temporarily at ININ as IAEA expert.     

A new method for99mTc generator preparation

The authors report here a new approach for making^99mTc generators based on neutron irradiation of metallic molybdates and direct elution eliminating intermediate chemical processing steps. This approach tested using zirconium molybdate was found to yield^99mTc with good yield and purity. This seems to be the simplest way of making column type^99mTc generator even using low flux reactors and merits further detailed evaluation.     

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.     

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.     

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.     

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.     

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.