99mTc Elution Research Articles

Sorption behavior of low specific activity 99Mo on Ti- and Zr-xerogels as an alternative to fission-based 99Mo/99mTc generators

Abstract In order to contribute to the sufficient supply of clinical 99mTc(VII), the sorption behavior of neutron-produced 99Mo(VI) was investigated on synthetized single and binary Ti and Zr xerogels treated at different temperatures, under normal operating conditions. Materials were prepared by the sol–gel method and characterized by several techniques. Sorption batch systems were performed using 99Mo radiotracer to determine the metallic affinity as a function of pH, and a methodology was developed in order to obtain the maximum capacities by surface saturation, where the Ti-388, TiZr-388 (3:1) and Zr-388 samples showed the most noteworthy sorption behaviors (33.1 ± 0.34 mg/g at pH ∼ 6.0, 31.7 ± 0.27 mg/g at pH ∼ 6.5, and 23.5 ± 0.61 mg/g at pH ∼ 6.8, respectively). The molybdenum-99 sorption behavior was also studied by fitting to the Freundlich and Langmuir models, and all xerogels could be described as heterogeneous materials with favorable 99Mo sorption properties. Finally, preliminary studies of clinical-scale 99Mo/99mTc generators were performed, the results revealed the next maximum 99mTc elution yield order Ti-388 (89.6 %) > TiZr-388 (3:1) (86.7 %) > Zr-388 (77.7 %).

A cerium-based metal-organic framework as adsorbent for the 99Mo/99mTc generator

The cerium-based metal–organic framework UiO-66 (Ce) was examined as a potential adsorbent for the 99Mo/99mTc generator. The results showed that the adsorbent had an outstanding adsorption performance, reaching up to 475 mg/g adsorption capacity at pH 3. An adsorption mechanism was proposed, where the adsorption was governed by hydrogen bonds, Ce-O-Mo coordination, π-anions and electrostatic interaction. Additionally, the adsorbent exhibited excellent radiation stability and good adsorption performance when radioactive 99Mo was applied. A 99Mo/99mTc generator was fabricated with UiO-66 (Ce) as adsorbent and its performance was evaluated over two weeks. The elution results showed that 92 ± 3% of 99mTc elution efficiency could be obtained with negligible cerium breakthrough, showing the great potential of UiO-66 (Ce) as adsorbent for 99Mo/99mTc generators.

Dynamic properties on 99Mo adsorption and 99mTc elution with alumina columns

The Mo adsorption/99mTc elution properties of alumina used as Mo adsorbents are examined for the development of 99Mo/99mTc generators using 99Mo produced by the (n, γ) method. MoO3 is irradiated by the Kyoto University Research Reactor (KUR). The alumina columns are filled with three types of alumina made from different raw materials. In this paper, elongated tubes are used as columns and the properties under Mo dynamic adsorption conditions on alumina are compared with those under static adsorption conditions. The results obtained suggest that the 99Mo/99mTc ratio specified by the Minimum Requirements for Radiopharmaceuticals of Japan (MRRP) is greatly affected by the method of adsorbing Mo on alumina.

Adsorption of molybdenum on Zr-based MOFs for potential application in the 99Mo/99mTc generator

The potential of the metal–organic framework UiO-66 and its functionalized derivatives for their utilization in the 99Mo/99mTc generator was assessed. Molybdenum adsorption experiments, structure characterization, molecular simulations and column experiments with molybdenum-99 were carried out. The results showed that the maximum molybdenum adsorption capacity achieved for UiO-66 was 335 mg g−1. Adsorption on the surface of the UiO-66 occurs via electrostatic interaction and DFT calculations verified the enhanced affinity between the adsorbents and the molybdenum ions by Zr-O-Mo coordination, anion-π as well as hydrogen bonds. In addition, the performance of a 99Mo/99mTc generator fabricated with Form-UiO-66 was evaluated. The results showed that adsorption was comparable with the experiments using non-active molybdenum and that the 99mTc elution efficiency of around 70% could be achieved without zirconium breakthrough.

99Mo/99mTc Radioisotope Generator Based on Zirconium Selenomolybdate as Column Matrix

Zirconium selenomolybdate gel matrices were prepared by mixing solutions of zirconium oxychloride, selenous acid, and sodium molybdate in different manners. The elution of the generated 99mTc radioactivity from the obtained zirconium selenomolybdate-99Mo matrices was studied using small chromatographic columns of the matrix. 6 g of zirconium selenomolybdate-99Mo matrix dried at 50°C, packed in a glass column (1.1 cm i.d.), was eluted by passing 10 mL of 0.9% NaCl at a flow rate of 1 mL min−1 and ambient temperature (∼25°C). The 99mTc elution yield of 77.1% was obtained. Radionuclidic, radiochemical, and chemical purity of the eluate proved to be suitable for use in medical applications.

New way to produce medical isotope wins U.S. approval

U.S. regulators are giving the green light to a new technology to produce technetium-99m, the most widely used radioisotope for medical imaging, without relying on weapons-grade highly enriched uranium. Earlier this month, FDA approved the RadioGenix System, a product of NorthStar Medical Radioisotopes of Beloit, Wis. The technology involves conversion of molybdenum-98 via neutron bombardment or of 100Mo in a linear accelerator to 99Mo. Next, 99Mo is processed into a form that allows elution of 99mTc, its daughter radionuclide, according to the Nuclear Regulatory Commission. For more than a quarter century, U.S. supplies of 99mTc involved shipping enriched uranium out of the country for irradiation and then importing the resulting 99Mo, FDA Commissioner Scott Gottlieb says. The foreign facilities that performed the irradiation, he says, “were vulnerable to unforeseen shutdowns or closures.” The Nuclear Regulatory Commission is developing guidance for facilities using the RadioGenix system and will license the new

New way to produce medical isotope wins U.S. approval

U.S. regulators are giving the green light to a new technology to produce technetium-99m, the most widely used radioisotope for medical imaging, without relying on weapons-grade highly enriched uranium. Earlier this month, FDA approved the RadioGenix System, a product of NorthStar Medical Radioisotopes of Beloit, Wis. The technology involves conversion of molybdenum-98 via neutron bombardment or of 100Mo in a linear accelerator to 99Mo. Next, 99Mo is processed into a form that allows elution of 99mTc, its daughter radionuclide, according to the Nuclear Regulatory Commission. For more than a quarter century, U.S. supplies of 99mTc involved shipping enriched uranium out of the country for irradiation and then importing the resulting 99Mo, FDA Commissioner Scott Gottlieb says. The foreign facilities that performed the irradiation, he says, “were vulnerable to unforeseen shutdowns or closures.” The Nuclear Regulatory Commission is developing guidance for facilities using the RadioGenix system and will license...

Preparation and characterization of iron(III) 99Mo-molybdate(VI) gels for the assessment of 99mTc elution performance

Abstract New iron(III) 99Mo-molybdate(VI) gels (Fe99Mo) of high Mo content were prepared by the precipitation/filtration method. 99Mo–MoO3 dissolved in NaOH was added to aqueous solutions of Fe(NO3)3 at Mo/Fe mole fractions ~2.21 and 1.99 with continuous stirring at ambient room temperature. Two different Fe99Mo were precipitated from the mixed solutions adjusted at pH 2 and 4.7. The amount of water of hydration increased with the increasing the gel settling time and pH of the mixed solution. The matrices were characterized by radiometric, XRD, SEM, XRF, FT-IR, TGA, and DTA measurements. Small chromatographic columns of 2.0 g Fe99Mo containing ≥800 mg Mo tagged with 740 MBq 99Mo were eluted with 5 mL saline solution. Highly reproducible 99mTc elution indices suitable for preparation of 99Mo/99mTc generators were achieved from generator supported with 0.5 g Al2O3 filter. Elution performance of 99mTc radionuclide was highly dependent on the gel structural properties.

Advanced prospects for the preparation of zirconium [99Mo]molybdate(VI) gel from diluted reactants and 99m Tc elution performance

Zirconium [99Mo]molybdate(VI) gel (ZrMo) was prepared from dilute mixed solutions of zirconium oxychloride and [99Mo]molybdate at pH 4.7. Paramolybdate(VI) anions were attracted to the positively charged surface of zirconia(IV) particulates (PZC at pH 7.2). The postulated reaction mechanism and gel formula were verified by radiometric analysis, X-ray diffraction, scanning electron microscopy, TGA, DTA, IR spectroscopy, and X-ray fluorescence analysis. 99mTc elution from ZrMo dried at 50 and 200°C was investigated. Reproducibly high 99mTc elution yield with high levels of radionuclidic, radiochemical, and chemical purity was achieved from the gel dried at 50°C. Correlation between structural properties of ZrMo and 99mTc elution performance was discussed.

Sorption of Mo(VI) on zirconium molybdosilicate gel and potential application as a 99Mo/99m Tc generator

Sorption of Mo(VI) from aqueous nitrate solutions onto zirconium molybdosilicate (ZrMoSi) gel was studied using 99Mo radiotracer. The acid–base titration curve showed that the prepared ZrMoSi gel was an amphoteric material with the point of zero charge (PZC) at pH 2.5. The highest distribution coefficient (600 mL g–1) of 99Mo(VI) on ZrMoSi from nitrate media was achieved at pH 2.1. The sorption kinetics of 99Mo(VI) onto ZrMoSi obeyed the pseudo-second-order model. The breakthrough sorption capacity of ZrMoSi gel was found to be 4.25 × 10–2 [mmol Mo(VI)] g–1. The prepared 99Mo/99mTc chromatographic column generator showed a good performance: The 99mTc elution yield was 87.7%, pH of the eluate ranged from 5.6 to 7.2, and the radionuclidic purity of the eluted 99mTc was >99.99% with a radiochemical purity of 98.31% (as 99mTcO4–).

Preparation and performance of 99Mo/99mTc chromatographic column generator based on zirconium molybdosilicate

Abstract Zirconium molybdosilicate (ZrMoSi) gel prepared using 99Mo radiotracer via peroxo route was used as a base material for 99Mo/99mTc column generator. The 99mTc elution yield and 99Mo breakthrough in the eluate were studied as a function of the pH-value of gel precipitation, gel drying temperature and Zr:Mo:Si molar ratio. Precipitation pH-value of 2, drying temperature of 100 ℃ and Zr:Mo:Si molar ratio of 0.5:0.5:1 were found to be the optimum conditions achieving 99mTc elution yield of 82% and 99Mo breakthrough of 1.0E-3%. The gel prepared with the optimum conditions was characterized by BET surface area and pore size analyzer, IR spectroscopy, thermal analysis (TGA and DTA), XRD, XRF and FESEM. Technetium-99m eluted from the optimum ZrMoSi 99Mo/99mTc generator was found to have a high radiochemical purity (98% as 99mTcO4 – ) and chemical purity meeting criteria of clinical grade.

Mechanism of 99Mo adsorption and 99mTc elution from zirconium-based material in 99Mo/ 99mTc generator column using neutron-irradiated natural molybdenum

The 99Mo adsorption and 99mTc elution mechanism were investigated using SEM–EDS to analyze the elemental composition of the adsorbent surfaces. From the changes of element composition, it was found that molybdate ions were adsorbed into the adsorbent by ion exchange with Cl− ion in the material. It was also revealed that 99mTc can be eluted in high oxidation state since the 99mTc in lower oxidation state easily made coordination bonds with other elements in the adsorbent.

A Mass-Production Process of a Highly Pure Medical Use 99mTc from Natural Isotopic Mo(n, γ) 99Mo without Using Uranium

A new method to produce highly pure 99mTc of maximum 500Ci(1.85e＋13Bq) per batch from a low specific activity 99Mo made from natural-Mo(n, γ) method is presented in this study.Authors developed a novel procedure to provide 99mTc of high specific activity and purity from 99Mo with a low specific activity obtained by the(n, γ) method. This process named TcMM(technetium master milker) with a new principle found out by the authors involves the selective adsorption of 99mTc onto an activated charcoal column, followed by an elution of 99mTc by warm alkaline solution, and final purification through an alumina column, which would be applicable to routine production of a large amounts of 99mTc from natMo(with 99Mo) within a short processing time and with a low cost.By the experiment using a high radioactivity of 99Mo of 1e＋12Bq levels, a highly pure 99mTc free from natMo(with 99Mo) was obtained in a sterile saline solution within 30 - 50min. as the chemical form of 99mTcO4−, and the average 99mTc milking rate repeated 10 times got 93.5% and the radiochemical purity of the range of 6N - 7N.In the labeling experiments using several radiopharmaceutical kits,99mTc collected from the TcMM process gave the target medicines in a highly radiochemical purity.As the result of investigating the disposition behaviors of the above-mentioned 99mTc-pharmaceuticals using small animals(mouse), 99mTc collected from TcMM gave the same result as it eluted from the conventional 99mTc generator.The findings in this study suggest that the present method using natural isotopic 98Mo(n, γ)99Mo reaction would constitute as an alternative to the Fission Method using HEU to provide 99mTc useful for clinical studies.

Preparation and characterization of cerium(IV) tellurium molybdate gel and its application as a bed for chromatographic <sup>99</sup>Mo/<sup>99m</sup>Tc generator

Cerium(IV) tellurium molybdate was prepared as a new gel bed for chromatographic 99Mo/99mTc generator. The gel material prepared with the optimum conditions was characterized with IR spectroscopy, thermal analysis, XRD, EDX and FESEM. The highest precipitation yield of 99Mo within the formed gel was found to be 97.6 % at a Ce:Te:Mo molar ratio of 1:0.2:1. The prepared 99Mo/99mTc chromatographic column based on Ce(IV) tellurium molybdate gel bed showed a good performance. The 99mTc elution yield was 77.8±3.0 % with a radionuclidic purity of ≥ 99.99 %, radiochemical purity of 96.5±1.3 % (as 99mTcO4-) and pH-value in the range of 5-7. Molybdenum and cerium levels in 99mTc eluates did not exceed 1 and 0.3 ppm, respectively, while no tellurium was detected.

Adsorption of 99m Tc on aluminum oxide

Adsorption of 99mTc under static and dynamic conditions on aluminum oxides subjected to various acid treatments at pH from 7.29 to 1.26 (until the reaction of the oxide with the acid fully ceased) was studied. In batch experiments, the maximal adsorption of 99mTc, more than 30% of the radionuclide activity, is attained with the oxide that absorbed 2 × 10−4 mol g−1 acid. The “rate” of linear migration of 99mTc in a chromatographic column in the course of elution with a 0.9% NaCl solution under the conditions of limiting saturation of the oxide with the acid is 0.49–0.52 cm ml−1. It is concluded that the observed deceleration of the 99mTc elution from the generator column is due to its “braking” by active sites of the oxide. Upon reduction of 99mTc with bivalent tin, its adsorption increases to 93.53%. The results obtained are of interest for the development of procedures for depositing 99mTc onto the surface of nanosized colloidal particles of aluminum oxide for their subsequent use in medical diagnostics.

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.

Importance of precise determination of technetium-labeled DISIDA concentrations for in vitro hepatocellular transport studies

Technetium 99m-labeled diisopropyliminodiacetic (acid [ 99mTc]DISIDA) has been used extensively in the evaluation of hepatobiliary diseases. As a result of investigation into transport mechanisms of [ 99mTc]DISIDA, we undertook to determine precise concentrations of this compound in the standard clinical formulation. Calculations based on published formulas were used. These take into account column efficiency, the time since the previous elution of 99mTc from the 99Mo column, and the total quantity of 99mTc eluted. Primary cultures of rat hepatocytes were used to evaluate the transport of Na 99mTcO 4 and the 99mTc-labeled DISIDA monomer. Pertechnetate was not taken up by the hepatocytes, the amount of [ 99mTc]DISIDa taken up was not dependent on the concentration of DISIDA but rather on the concentration of technetium, when the DISIDA/ 99mTc ratio was varied in the culture medium. We conclude that calculation of the total technetium concentration is necessary to determine the amount of compound taken up by the liver, and to interpret kinetic studies of hepatocellular transport mechanisms.

Comparative study of 99Mo-labeled and neutron irradiated zirconium molybdate gels

Elution of 99mTc with physiological saline solution was studied through columns packed with: (a) 99Mo-labeled and (b) neutron irradiated zirconium molybdate gels. It was found that 99mTc and 99Mo behave very differently in each one of the systems used: Through column (a) 99mTc was always eluted in high yields (90%). Initially the gel was not completely insoluble, but it was insolubilized under the effect of the eluent. Through column (b) only 20% of the available 99mTc eluted on the first day and the neutron irradiated zirconium molybdate samples were always partially soluble unstable under elution conditions. These differences were probably due to the chemical effects produced by 98Mo(n, γ) 99Mo reaction in neutron irradiated zirconium molybdate samples. Attempts to insolubilize the recoiled 99Mo in the solid by annealing showed no significant differences in the elution behavior.

Tc-99m-HMPAO labelled human platelets: in vitro and in vivo results

The lipophilic 99mTc-HMPAO complex can be used for labelling platelets as well as granulocytes. Platelets were isolated according to standard isolation procedures for the evaluation of the optimal labelling parameters. The labelling efficiency (%) depends on incubation temperature (22 degrees C: 40%: 37 degrees C: 50%), incubation time (3 min: 20%, 25 min: 55%) and the incubation medium (plasma: 40%; saline 50%). The 60 min 99mTc elution out of the platelets ranged around 8%. The platelet recovery used as a quality control parameter is around 25% +/- 4% and is stable for at least 240 min. The high elution rate out of the platelets leads to renal excretion of the label and hence to significant kidney and bladder activity. Intestinal excretion of the label can also be frequently demonstrated. Fresh thrombotic lesions can normally be detected 4 h after reinjection of the labelled platelets, and in some patients as early as 1 h after reinjection. In conclusion, 99mTc-HMPAO seems to be a promising platelet label for imaging thrombotic lesions but not for platelet survival studies, because of the short physical half life of 99mTc.

Radiolabelling of human platelets with 99mTc-HMPAO.

The optimum conditions for labelling platelets with lipophilic 99mTc-hexamethyl propylene amine oxime (99mTc-HMPAO) were evaluated. An aseptic closed system was used throughout the procedure in patient studies. 48 ml blood were withdrawn into 12 ml ACD using sterile 60 ml plastic syringes. After mixing, the blood was transferred to sterile 10 ml vacuum tubes and platelets were isolated according to standard centrifugation procedures. The labelling efficiency was not dependent upon incubation temperature (22 degrees C, 37 degrees C) but was greater in saline than in the presence of plasma. The labelling efficiency increased with time up to 60 min in saline. The elution of 99mTc from platelets was about 25% in plasma milieu in vitro but did not increase with time during 160 min. 5 patients with verified fresh deep vein thrombosis in the lower leg were imaged after injection of labelled autologous platelets. All 4 of the patients without anticoagulant therapy showed positive uptake of 99mTc-HMPAO-labelled platelets, but the 5th patient--under heparin therapy--was negative in scintigraphy. Our results are encouraging and 99mTc-HMPAO-labelled platelets offer a promising tool for evaluating various clinical situations.