Littérature scientifique sur le sujet « 99mTc, Mo target, cyclotron »

Technetium-99m (99mTc) is the most used radionuclide worldwide in nuclear medicine for diagnostic imaging procedures. 99mTc is typically extracted from portable generators containing 99Mo, which is produced normally in nuclear reactors as a fission product of highly enriched Uranium material. Due to unexpected outages or planned and unplanned reactor shutdown, significant 99mTc shortages appeared as a problem since 2008 The alternative cyclotron-based approach through the 100Mo(p,2n)99mTc reaction is considered one of the most promising routes for direct 99mTc production in order to mitigate potential 99Mo shortages. The design and manufacturing of appropriate cyclotron targets for the production of significant amounts of a radiopharmaceutical for medical use is a technological challenge. In this work, a novel solid target preparation method was developed, including sputter deposition of a dense, adherent, and non-oxidized Mo target material onto a complex backing plate. The latter included either chemically resistant sapphire or synthetic diamond brazed in vacuum conditions to copper. The target thermo-mechanical stability tests were performed under 15.6 MeV proton energy and different beam intensities, up to the maximum provided by the available GE Healthcare (Chicago, IL, USA) PET trace medical cyclotron. The targets resisted proton beam currents up to 60 µA (corresponding to a heat power density of about 1 kW/cm2) without damage or Mo deposited layer delamination. The chemical stability of the proposed backing materials was proven by gamma-spectroscopy analysis of the solution obtained after the standard dissolution procedure of irradiated targets in H2O2.

The most important radioisotope for nuclear medicine is [Formula: see text]Tc. After the supply crisis of [Formula: see text]Mo starting in 2008, the availability of [Formula: see text]Tc became a worldwide concern. Alternative methods for producing the medical imaging isotope [Formula: see text]Tc are actively being developed around the world. The reaction [Formula: see text]Mo(p, 2n)[Formula: see text]Tc provides a direct route that can be incorporated into routine production in nuclear medicine centers that possess medical cyclotrons for production of other isotopes, such as those used for Positron Emission Tomography. This paper describes a new approach for manufacturing targets for the (p, 2n) nuclear reaction on [Formula: see text]Mo and the foundation for the subsequent commercial separation and purification of the [Formula: see text]Tc produced. Two designs of targets are presented. The targets used to produce [Formula: see text]Tc are subject to a number of operational constraints.They must withstand the temperatures generated by the irradiation, accommodate temperature gradients from cooling system of the target, must be resilient and must be easily post-processed to separate the [Formula: see text]Tc. After irradiation, the separation of Tc from Mo was carried out using an innovative two-step approach. The process described in this paper can be automated with modules that easily fit in standard production hot cells found in nuclear medicine facilities.

A closed-loop technology aiming at recycling the highly 100Mo-enriched molybdenum target material has been developed in the framework of the international research efforts on the alternative, cyclotron-based 99mTc radionuclide production. The main procedure steps include (i) 100Mo-based target manufacturing; (ii) irradiation under proton beam; (iii) dissolution of 100Mo layer containing 9×Tc radionuclides (produced by opened nuclear reaction routes) in concentrated H2O2 solution; and (iv) Mo/Tc separation by the developed radiochemical module, from which the original 100Mo comes as the “waste” alkaline aqueous fraction. Conversion of the residual 100Mo molybdates in this fraction into molybdic acids and MoO3 has been pursued by refluxing in excess of HNO3. After evaporation of the solvent to dryness, the molybdic acids and MoO3 may be isolated from NaNO3 by exploiting their different solubility in water. When dried in vacuum at 40 °C, the combined aqueous fractions provided MoO3 as a white powder. In the last recovery step MoO3 has been reduced using a temperature-controlled reactor under hydrogen overpressure. An overall recovery yield of ~90% has been established.

AbstractA semi-automated purification module for the cyclic separation of 99mTc was designed for production of [99mTc]TcO4– from γ irradiated 100Mo target. The separation process was carried out by using a 3-column purification system and the final product, [99mTc]TcO4–, was obtained in a total volume of 7 mL. To confirm proper separation achieved for 99mTc, a radio-labeling procedure using DTPA chelator was performed. The radiochemical purity was higher than 95%, which meets the strict radiopharmaceutical requirements. The yielded 99mTc can be separated with high efficiency from Mo in a quick and repeated way. Loss of 99mTc radioactivity during such a three-column separation process was not larger than 10%.

Aluminum (Al) is often used to house a molybdenum oxide (MoO3) target for neutron or proton-produced technetium-99m (99mTc) radioisotope. During neutron or proton bombardment of an Al body, residual radioisotopes could be generated following nuclear reactions between the incoming particles and the Al body. In this research, residual radioisotopes produced following nuclear reactor based-neutron irradiation of Al body were experimentally measured using a portable gamma ray spectroscopy system; whereas TALYS 2015 calculated data were used to evaluate various nuclear reactions for the by-product identification. As a comparison, Al body used in a cyclotron-based 99mTc production was also analyzed. Experimental data indicated that relatively long-lived radioisotopes such as 26Al, 22Na and 24Na were identified in the Al body following nuclear reactor-based 99mTc production, whereas the presence of 27Mg radioisotope was, for the first time, experimentally detected in both the Al bodies for nuclear reactor-based and cyclotron-based 99mTc production. A special safety attention should be paid to the radiation workers when producing 99mTc using a nuclear reactor since it generates 26Al (half life = 716,600 years).

Magnetron sputtering is proposed here as an innovative method for the deposition of a material layer onto an appropriate backing plate for cyclotron solid targets aimed at medical radioisotopes production. In this study, a method to deposit thick, high-density, high-thickness-uniformity, and stress-free films of high adherence to the backing was developed by optimizing the fundamental deposition parameters: sputtering gas pressure, substrate temperature, and using a multilayer deposition mode, as well. This method was proposed to realize Mo-100 and Y-nat solid targets for biomedical cyclotron production of Tc-99m and Zr-89 radionuclides, respectively. The combination of all three optimized sputtering parameters (i.e., 1.63 × 10−2 mbar Ar pressure, 500 °C substrate temperature, and the multilayer mode) allowed us to achieve deposition thickness as high as 100 µm for Mo targets. The 50/70-µm-thick Y targets were instead realized by optimizing the sputtering pressure only (1.36 × 10−2 mbar Ar pressure), without making use of additional substrate heating. These optimized deposition parameters allowed for the production of targets by using different backing materials (e.g., Mo onto copper, sapphire, and synthetic diamond; and Y onto a niobium backing). All target types tested were able to sustain a power density as high as 1 kW/cm2 provided by the proton beam of medical cyclotrons (15.6 MeV for Mo targets and 12.7 MeV for Y targets at up to a 70-µA proton beam current). Both short- and long-time irradiation tests, closer to the real production, have been realized.

The [Formula: see text]Tc isomer was produced using the [Formula: see text] reaction on highly enriched [Formula: see text]Mo samples. The Thick Target Yields were determined in the energy range from 16 MeV to 26 MeV and compared with the values calculated using the most recent cross-section recommendations from the literature. The generated impurities were also determined. It was shown that for 99.815 ± 0.010% enriched samples, only reactions induced on [Formula: see text]Mo are of importance. The ratio of the number of atoms of [Formula: see text]Tc to all produced Tc nuclei was studied as a function of irradiation time and bombarding energy.

High specific activity is a necessity in the fabrication of 99Mo/99mTc radioisotope generators. Recoil reaction, or the Szilard-Chalmers effect, is a method that could be used as an alternative method for increasing specific activity in radioisotope production in light of tightening regulation of highly enriched uranium (HEU) irradiation. Phthalocyanine compounds are usually used as the target material in recoil reactions for the production of high specific radioisotope activity via the (n,γ) reaction. Molybdenum phthalocyanine (Mo-Pc) could be a promising target material in recoil reactions for producing high specific activity of 99Mo. Mo-Pc was synthesized via solid-state reaction between ammonium heptamolybdate and phthalonitrile in a reflux system at 300 °C for 3 h. This optimum condition was identified after performing several variations of temperature and time of reaction, considering FTIR spectra, the yield of product and melting point of the product. XRD measurement showed that Mo-Pc synthesized at optimum condition was free from MoO2, phthalimide and unreacted molybdenum. Mo-Pc has UV-vis properties of Q-band absorption between 600 and 750 nm when dissolved in tetrahydrofuran, dimethylformamide and trifluoroacetic acid. Splitting at absorption peak in tetrahydrofuran and dimethylformamide solution indicated that protonation had occurred. This split peak did not appear in a trifluoroacetic acid solution. In the preliminary study of irradiation of 1 g Mo-Pc at 3.5x1012 n cm–2 s–1 neutron flux, followed by dissolution in tetrahydrofuran and extraction of Mo-99 into NaOH, we obtained Mo-99 solution with a specific activity of 682.35 mCi/g Mo, this being 254.61 times higher than in the regular MoO3 target.

Cyclotron production of 99mTc through the 100Mo(p,2n)99mTc reaction1 is being actively investigated as an alternative to reactor-based approaches. A challenge facing cyclotron pro-duction of clinical-quality 99mTc is that proton bombardment of Mo targets results in production of a number of additional Tc and non-Tc isotopes through various reaction channels.2,3 While non-Tc products can be chemically re-moved, other Tc radioisotopes cannot and will therefore degrade radionuclidic purity and contribute to patient radiation dose.5 The radionuclidic purity of cyclotron-produced 99mTc depends on the nuclear cross section governing each reaction channel, the proton current and energy distribution, duration of bombardment, target thickness and isotopic composition. Although conditions that minimize dose from radioactive Tc impurities have been identified,5 cyclotron performance and thus irradiation conditions may randomly fluctuate between and/or during production runs. Fluctuations of certain parameters, for example the total number of bombarding protons, are expected to have little influence on radionuclidic purity, whereas fluctuations in beam energy, target thickness and isotopic composition may dramatically affect the relative amounts of 93gTc, 94gTc, 95gTc, and 96gTc impurities. It is critical to quantify relationships between potential fluctuations and the reproducibility and consistency of the radionuclidic purity of cyclotron-produced 99mTc to guide development and optimization of target preparation, irradiation, and processing techniques. The purpose of this work is to present a mathematical formalism for quantifying the relation-ship between random fluctuations in Mo target thickness and variability of proton-induced nuclear reaction rates for enriched Mo targets. In this study, we use 96gTc as an example of impurity which can potentially contribute to increased patient dose for patients injected with cyclotron-produced 99mTc.4 Herein, we apply the developed formalism to both the 96Mo(p,n)96gTc and the 100Mo(p,2n)99mTc reaction channels, however, the same approach can be applied to any reaction channel of interest.

Introduction Alternative methods for producing the medical imaging isotope 99mTc are actively being developed around the world in anticipation of the imminent shutdown of the National Research Universal (NRU) reactor in Chalk River, Ontario, Canada and the high flux reactor (HFR) in Petten, Holland that together currently produce up to 80 % of the world’s supply through fission. The most promising alternative methods involve accelerators that focus Bremsstrahlung radiation or protons on metallic targets comprised of 100Mo and a supporting material used to conduct heat away during irradiation. As an example, the reaction 100Mo(p,2n)99mTc provides a direct route that can be incorporated into routine production in regional nuclear medicine centers that possess medical cyclotrons for production of other isotopes, such as those used for Positron Emission Tomography (PET). The targets used to produce 99mTc are subject to a number of operational constraints. They must withstand the temperatures generated by the irradiation and be fashioned to accommodate temperature gradients from in situ cooling. The targets must be resilient, which means they cannot disintegrate during irradiation or post processing, because of the radioactive nature of the products. Yet, the targets must be easily post-processed to separate the 99mTc. In addition, the method used to manufacture the targets must not be wasteful of the 100Mo, because of its cost (~$2/mg). Any manufacturing process should be able to function remotely in a shielded space to accommodate the possibility of radioactive recycled target feedstock. There are a number of methods that have been proposed for large-scale target manufacturing including electrophoretic deposition, pressing and sinter-ing, electroplating and carburization [1]. How to develop these methods for routine production is an active business [2,3]. From the industrial perspective, plasma spraying showed promising results initially [4], but the process became very expensive requiring customized equipment in order to reduce losses because of overspray,which also required a large inventory of expen-sive feedstock. In this paper we report the ex-perimental validation of an industrial process for production of targets comprising a Mo layer and a copper support. Materials and methods Target Design Targets have been manufactured for irradiation at 15 MeV. Two targets are shown in FIG. 1: one as-manufactured and another after irradiation; no visible changes were observed following irradiation. The supporting circular copper (C101) disks have diameters of 24 mm and thickness of 1.6 mm. The molybdenum in the center of the target is fully dense with thickness 230 μm determined from SEM cross-sections.Targets have also been manufactured for irradi-ation in a general-purpose target holder designed to be attached to all makes of cyclotrons found in regional nuclear medicine centers. The elliptical targets were designed for high-volume production of 99mTc with 15 MeV protons at currents of 400 µA with 15% collimation [4]. The elliptical shape reduces the heat flux associated with high current sources. The cooling channels on the back of the target are designed to with-stand the high temperature generated during Irradiation. A thermal simulation of expected temperatures during irradiation is shown in FIG. 3. The center of the target is expected to reach 260 oC during irradiation. The elliptical targets were formed from a 27 mm C101 copper plate with width 22 mm and length 55 mm. The molybdenum in the center of the target is fully dense with thickness 60 m de-termined from SEM cross-sections. FIG. 4 shows the molybdenum deposition in the center of the target in a form of an ellipse (38×10 mm). Results and Conclusions Circular targets have been produced and suc-cessfully irradiated for up to 5 h with a proton beam with energy 15 MeV and current 50 µA. (FIG. 1). The targets were resilient. Before irradi-ation the targets were subjected to mechanical shock tests and thermal gradients with no ob-servable effect. After irradiation there was no indication of any degradation. The manufacturing process produced 20 consistently reproducible targets within an hour with a molybdenum loss of less than 2 %. After irradiation the targets were chemically processed and the products characterized by Ge-HP gamma spectrometry. Only Tc isotopes were found. No other contami-nants were identified after processing. The de-tails of the separation and purification are de-scribed elsewhere [5]. Circular targets suitable for low-volume produc-tion of 99mTc have been manufactured and test-ed. The targets have been shown to meet the required operation constraints: the targets are resilient withstanding mechanical shock and irradiation conditions; they are readily produced with minimal losses; and post-processing after irradiation for 5 h has been shown to produce 99mTc. Elliptical targets suitable for high-volume pro-duction of 99mTc with high power cyclotrons have been manufactured (FIG. 4). Like the circular targets, the elliptical targets are readily pro-duced with minimal losses and are able to with-stand mechanical shock and thermal gradients; however, they have yet to be irradiated.

Introduction Technetium-99m, supplied in the form of 99Mo/99mTc generators, is the most widely used radioisotope for nuclear medical imaging. The parent isotope 99Mo is currently produced in nuclear reactors. Recent disruptions in the 99Mo supply chain [1] prompted the development of methods for the direct accelerator-based production of 99mTc. Our approach involves the 100Mo(p,2n)99mTc reaction on isotopically enriched molybdenum using small medical cyclotrons (Ep ≤ 20 MeV), which is a viable method for the production of clinically useful quantities of 99mTc [2]. Multi-Curie production of 99mTc requires a 100Mo target capable of dissipating high beam intensities [3]. We have reported the fabrication of 100Mo targets of both small and large area tar-gets by electrophoretic deposition and subsequent sintering [4]. As part of our efforts to further enhance the performance of molybdenum targets at high beam currents, we have developed a novel target system (initially de-signed for the GE PETtrace cyclotron) based on a pressed and sintered 100Mo plate brazed onto a dispersion-strengthened copper backing. Materials and Methods In the first step, a molybdenum plate is produced similarly to the method described in [5] by compacting approximately 1.5 g of commercially available 100Mo powder using a cylindrical tool of 20 mm diameter. A pressure between 25 kN/cm2 and 250 kN/cm2 is applied by means of a hydraulic press. The pressed molybdenum plate is then sintered in a reducing atmosphere (Ar/2% H2) at 1,700 oC for five hours. The resulting 100Mo plates have about 90–95 % of the molybdenum bulk density. The 100Mo plate is furnace brazed at ~750 oC onto a backing manufactured from a disperse on strengthened copper composite (e.g. Glidcop AL-15) using a high temperature silver-copper brazing filler. This process yields a unique, mechanically and thermally robust target system for high beam power irradiation. Irradiations were performed on the GE PETtrace cyclotrons at LHRI and CPDC with 16.5 MeV protons and beam currents ≥ 100 µA. Targets were visually inspected after a 6 hour, 130 µA bombardment (2.73 kW/cm2, average) and were found fully intact. Up to 4.7 Ci of 99mTc have been produced to date. The saturated production yield remained constant between 2 hour and 6 hour irradiations. Results and Conclusion These results demonstrate that our brazed tar-get assembly can withstand high beam intensities for long irradiations without deterioration. Efforts are currently underway to determine maximum performance parameters.

Introduction Technetium-99m, the daughter of 99Mo is the most commonly used radioisotope in nuclear medicine [1–2]. Current global crisis of 99Mo supply, aging of nuclear reactors and staggering costs force the search for alternative sources of 99mTc. Radioisotope Centre POLATOM joined the IAEA Coordinated Research Project on “Accelerator-based Alternatives to Non-HEU Production of 99Mo/99mTc”. The planned outcome of this project is development of 99mTc production method using the reaction of 100Mo(p,2n)99mTc [3] in Polish cyclotron. This work presents the results concerning preparation of 100Mo target for irradiation with protons. Material and Methods The manufacturing of Mo target was performed using pressing of molybdenum powder into pellets and its sintering in hydrogen atmosphere at 1600 oC [4]. For this purpose a tantalum and stainless steel plates were used as support. Several pellets using molybdenum powder with particles size of 2 µm in diameter were pressed at different values of pressure. Results and Conclusion The optimized parameters of pressing molyb-denum pellets with various sizes are given in TABLE 1. It was found that the pellets did not adhere neither to the tantalum nor stainless steel plates but they conducted electricity very well. Pellets prepared with higher pressure were more mechanically resistant, however application, even the highest used pressure did not ensure its satisfactory stability. In order to improve mechanical strength, pressed Mo pellets were sintered in hydrogen atmosphere at temperature of 1600 °C. As a result of this process dimensions of Mo pellets decreased: diameter by 13 %, thickness by 12 %, weight by 1.5 %, volume by 34 % while density increased by 50 %. The changes of these parameters are associated with reduction of molybdenum oxide and removal of oxygen from intermetallic space. It was confirmed by photos of microscopic cross section of pellets before and after sintering. It was observed, that after sintering Mo pellets got a metallic form with very high hardness and mechanical strength.