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 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.

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.

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.