Process, system, and apparatus for cyclotron production of technetium-99M

Abstract

The Company offers a process for producing technetium-99m from molybdenum-100 metal powder. The method includes irradiating a hardened sintered target plate coated with molybdenum-100 with cyclotron-generated protons, dissolving molybdenum atoms and technetium ions from the irradiated target plate with a H2O2 solution to form an oxide solution, increasing the pH of the oxide solution to about 14, passing the pH-adjusted oxide solution through a resin column to immobilize K[TcO4] ions, eluting the K2[MoO4] ions, eluting the bound K[TcO4] ions from the resin column, passing the eluted K[TcO4] ions through an alumina column to immobilize the K[TcO4] ions, washing the immobilized K[TcO4] ions with water, eluting the immobilized K[ToO4] ions with saline, and recovering the eluted Na[TcO4].

Description

[Technical field]

[0001] The present disclosure relates to processes, systems, and apparatus for the production of Technetium-99m. More particularly, the present disclosure relates to the production of Technetium-99m from Molybdenum-100 using accelerators such as cyclotrons. [Background technology]

[0002] Technetium-99m (hereafter referred to as Tc-99m) is one of the most widely used radioactive tracers in nuclear medicine diagnostic procedures. Tc-99m emits easily detectable gamma rays of 140 keV and has a half-life of only about 6 hours, limiting the patient's radiation exposure. Depending on the type of nuclear medicine procedure, Tc-99m is bound to a selected agent that carries Tc-99m to the required location where it is subsequently imaged by the radiation equipment. Common nuclear medicine diagnostic techniques include Tc-99m labeling into sulfur colloids for imaging of the liver, spleen, and bone marrow, into coarsely aggregated albumin for lung scans, into phosphonates for bone scans, into iminodiacetic acid for imaging of the hepatobiliary system, into glucoheptonic acid for renal and brain scans, into diethylenetriaminepentaacetic acid (DPTA) for brain and renal scans, into dimercaptosuccinic acid (DMSA) for renal cortex scans, into red blood cells for cardiac blood pool scans, into methoxyisobutylisonitrile (MIBI) for ventriculography, for imaging myocardial blood flow, and into pyrophosphate for imaging calcium deposits in injured hearts. Tc-99m is also very useful for detecting various forms of cancer, for example by identifying sentinel nodes, i.e. lymph nodes, draining the site of a cancer such as breast cancer or malignant melanoma, by first injecting a Tc-99m-labeled sulfur colloid and then a Tc-99m-labeled isosulfan blue dye. Immunoscintigraphy is particularly useful for detecting hard-to-find cancers and is based on labeling selected cancer cell-specific monoclonal antibodies with Tc-9m and scanning the subject's body with a radiological machine after the labeled monoclonal antibodies are injected.

[0003] Currently, the world's supply of Tc-99m for nuclear medicine is produced in nuclear reactors. First, molybdenum-99 (hereafter referred to as Mo-99), the parent nuclide of Tc-99m, is produced by fissioning enriched uranium in several nuclear reactors around the world. Mo-99 has a relatively long half-life of 66 hours, so it can be transported to hospitals around the world. Mo-99 is distributed in the form of a Mo-99 / Tc-99m generator device that uses column chromatography to extract and recover Tc-99m from the decaying Mo-99. The chromatography column is filled with acidic alumina (A12O3), into which Mo-99 is converted into molybdate MoO4 2- When Mo-99 decays, it turns into pertechnetate TcO4 - This is because its single charge is not tightly bound to the alumina column inside the generator device. The soluble Tc-99m is eluted by drawing normal saline through the column of immobilized Mo-99, resulting in saline that contains Tc-99m as pertechnetate and sodium as the balancing cation. The sodium pertechnetate solution can then be added at the appropriate concentration to the organ-specific drug "kit" being used, or can be used without drug labeling as [Tc-99m]O4 - For certain procedures requiring only sodium pertechnetate as the primary radiopharmaceutical, sodium pertechnetate can be used directly.

[0004] A problem with fission-based production of Tc-99m is that several of the reactors that produce the world's supply of Mo-99 are nearing the end of their useful lives. Currently, approximately two-thirds of the world's supply of Mo-99 is provided by two reactors: (i) the National Research Universal Reactor at Chalk River Laboratories in Ontario, Canada, and (ii) the Petten Reactor in the Netherlands. Both facilities were shut down for extended periods in 2009-2010, resulting in severe shortages of Mo-99 to medical facilities worldwide. Both facilities are now operational again, but significant concerns remain regarding the long-term reliability of the supply of Mo-99.

[0005] It is known that medical cyclotrons can produce small amounts of Tc-99m from Mo-100 for research purposes. Cyclotron-produced Tc-99m has recently been demonstrated to be comparable to reactor-produced Tc-99m when used in nuclear medicine imaging (Guerin et al., 2010, Cyclotron production of Tc-99m). 99mc 99m-Mo: An approach to the medical isotope crisis. J. Nucl. Med. 51(4):131-16N). However, analysis of the many published studies on the conversion of Mo-100 to Tc-99m reveals considerable discrepancies in terms of conversion efficiency, gamma-ray production, and purity (Challan et al., 2007, Thin target yields and Empire-II predictions in the accelerator production of technetium-99m. J. Nucl. Rad. Phys. 2:1-; Takacs et al., 2003, Evaluation of proton induced reactions on 100 Mo:New cross sections for production of 99m Tc and 99Mo.J.Radioanal.Nucl.Chem.257:195-201;Lebeda et al., 2012, New measurement of excitation functions for (p,x) reactions on nat Mo with special regard to the formation of 95m Tc, 96m+g Tc, 99m Tc and 99 Mo.Appl.Radiat.Isot.68(12):2355-2365;Scholten et al., 1999, Excitation functions for the cyclotron production of 99m Tc and 99 Mo.Appl.Radiat.Isot.51:69-80). [Summary of the invention]

[0006] Exemplary embodiments of the present disclosure relate to a process for producing Technetium-99m (Tc-99m) from Molybdenum-100 (Mo-100) by proton irradiation using an accelerator such as a cyclotron. Some exemplary embodiments relate to a system for carrying out the process of the present disclosure. Some exemplary embodiments relate to an apparatus including the system of the present disclosure.

[0007] The present disclosure will be described with reference to the following drawings: [Brief description of the drawings]

[0008] [Figure 1] 1 is a schematic flow chart outlining an exemplary process of the present disclosure. [Diagram 2] 1 is a top view of an exemplary elongated target plate according to one embodiment of the present disclosure. [Diagram 3] FIG. 3(a) is a cross-sectional side view and FIG. 3(b) is a cross-sectional end view of the exemplary target plate of FIG. [Figure 4] FIG. 4 is a perspective view of an exemplary target capsule device for mounting the exemplary target plate shown in FIGS. 2 and 3. [Diagram 5] FIG. 5 is a partial view of the top of the targeted capsule device of FIG. 4. [Figure 6] FIG. 6 is a cross-sectional side view of the targeted capsule device of FIG. 5. [Figure 7] FIG. 7 is a perspective view of an exemplary target pick-up device having a pusher component that engages the target capsule assembly device of FIGS. 4-6. [Figure 8] FIG. 8 is a cross-sectional side view of the target pick-up device of FIG. 7 engaged with a pusher component. [Figure 9] FIG. 15 is a perspective view of an exemplary receiving cell apparatus for engaging and cooperating with the target station apparatus shown in FIGS. 12-14. [Figure 10] FIG. 10 is a side view of the receiving cell apparatus shown in FIG. [Figure 11] FIG. 10 is a top view of the receiving cell apparatus shown in FIG. [Figure 12] 9 is a perspective view of an exemplary targeting station device for receiving the target pick-up device shown in FIGS. 7 and 8 engaged with the targeting capsule device shown in FIGS. 4-6. FIG. [Figure 13] FIG. 13 is a side view of the target station apparatus shown in FIG. 12. [Figure 14] FIG. 13 is a top view of the target station apparatus shown in FIG. 12. [Figure 15] FIG. 15(a) is a plan view, FIG. 15(b) is a top view, and FIG. 15(c) is a cross-sectional side view of the exemplary circular target plate of FIG. 15(a) according to one embodiment of the present disclosure. [Figure 16] FIG. 1 is a perspective view of an exemplary targeting capsule apparatus for mounting a circular target disk. [Figure 17] FIG. 17 is an end view of the targeted capsule device shown in FIG. 16. [Figure 18] FIG. 17 is a cross-sectional side view of the targeted capsule device shown in FIG. 16. [Figure 19] FIG. 2 is a perspective view of an exemplary target pick-up device engaged with a pusher component. [Figure 20] FIG. 20 is a cross-sectional side view of the target pickup device of FIG. 19. [Figure 21]FIG. 28 is a perspective view of an exemplary receiving cell apparatus for engaging and cooperating with the target station apparatus shown in FIGS. 24-27. [Figure 22] FIG. 22 is a side view of the receiving cell apparatus shown in FIG. 21. [Diagram 23] FIG. 22 is a top view of the receiving cell apparatus shown in FIG. 21. [Figure 24] 20 is a perspective view of an exemplary targeting station device for receiving the target pick-up device shown in FIG. 19 engaged with the targeting capsule device shown in FIGS. 16-18. [Diagram 25] FIG. 25 is a top view of the target station apparatus shown in FIG. 24. [Figure 26] 25 is a cross-sectional top view of the target station apparatus shown in FIG. 24 with an exemplary target cell apparatus delivered to a target housed in an unloaded position. [Figure 27] 25 is a cross-sectional top view of the target station apparatus shown in FIG. 24 with the exemplary target cell apparatus moved to a loading position. [Figure 28] FIG. 2 is a perspective view of an exemplary booster station shown in a disengaged mode. [Figure 29] FIG. 29 is a perspective view of the example booster station of FIG. 28 shown in an engaged mode. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] An exemplary embodiment of the present disclosure relates to a process for producing Tc-99m by low energy proton irradiation of Mo-100 using a proton beam generated by an accelerator such as a cyclotron. Suitable proton energies for the process of the present disclosure are from about 10 MeV to about 30 MeV incident on the target. A flow chart outlining an exemplary process is shown in FIG. 1. The process generally follows the following steps: 1) Processing a supply of concentrated Mo-100 metal powder to produce Mo-100 powder having a consistent particle size of less than about 10 microns. 2) A coating of the processed Mo-100 powder is deposited by electrochemical and / or electrophoretic deposition onto a target plate containing a transition metal. 3) The coated target plate is sintered in an inert atmosphere for about 2 hours to about 10 hours at a temperature of about 1200° C. to about 2000° C. 4) Securely engage the sintering target plate into the target holder. The target holder engaged with the sintering target plate is referred to herein as the target capsule assembly. 5) placing the target capsule assembly into a receiving cell apparatus where it is engaged by a target pick-up apparatus which cooperates with a target transport drive apparatus to deliver the target capsule assembly into a target station apparatus engaged to a cyclotron; and 6) irradiating the sintered target plate with a supply of accelerator generated protons in a substantially oxygen-free atmosphere. 7) Using a transfer drive apparatus to disengage the target capsule assembly from the target station and transfer the target capsule assembly into a receiving cell apparatus to separate and collect the molybdate and pertechnetate ions from the proton irradiated target plate. 8) Separating the pertechnetate ion from the molybdate ion and purifying and further processing the pertechnetate ion. These steps are carried out under precisely controlled environmental conditions to minimize loss of pertechnetate ion. 9) The molybdate ions are recovered, purified and in a suitable condition for reuse on the coated target plate.

[0010] Previous use of accelerators to produce Tc-99m from Mo-100 has focused on generating small quantities sufficient for research use and to compare the functionality of the Tc-99m produced in this way in medical diagnostic imaging with standard Tc-99m produced from Mo-99 using nuclear reactors. Commercially available enriched Mo-100 metal powders typically contain a mixture of particle sizes from less than one micron to more than one millimeter. Thus, the use of such powders to coat target backing disks or backing plates results in non-uniform distribution of Mo-100 across the plate surface, resulting in variability in the thickness of the Mo-100 deposition. Such variability can damage the target plate during proton irradiation, reduce the efficiency of conversion of molybdenum atoms to technetium atoms, and result in unpredictable production of pertechnetate ions. It is therefore common practice to press commercial grade Mo-100 powder with a pressure of about 25,000N to about 100,000N into pellets with a diameter of 6.0 to 9.5 mm. The Mo-100 pellets are then reduced in a hydrogen atmosphere at a temperature of 800°C to 900°C. Mo-100 is typically attached to the target backing disk by pressing or arc melting or electron beam melting either as commercial grade Mo-100 powder or as sintered Mo-100 pellets. Melting methods typically use currents of 40mA to 70mA applied in various sweep and focus patterns. As a result, the use of such powders and / or pellets to coat a target plate results in non-uniform distribution of Mo-100 across the plate surface, resulting in variations in the thickness of the Mo-100 deposit. Such variability leads to (i) damage to the target plate during proton irradiation, (ii) reduced efficiency of conversion of molybdenum atoms to technetium atoms, and (iii) unpredictable production of pertechnetate ions. Other problems commonly faced relate to the target disk itself. Targets commonly used for research-scale Tc-99m production in cyclotrons include small, thin disks of copper or tantalum, typically with diameters of about 5-6 mm. Such disks cannot be loaded with enough Mo-100 to enable large-scale production of Tc-99m.This is because the disks are mechanically fragile and may break or be destroyed under proton irradiation due to the very high levels of heat that are concomitantly generated. There are many challenges and problems that must be addressed in order to successfully ramp up Tc-99m production from Mo-100 using cyclotron-based systems. Problems related to molybdenum that must be addressed include (i) the inability to deposit thick layers of Mo-100 on target plates by galvanic plating from aqueous solutions, (ii) isotopically enriching the molybdenum to promote the production of specific technetium isotopes, and (iii) overcoming the need for concentrated acid solutions and the long times required to dissolve irradiated plates of molybdenum. Challenges that must be overcome to facilitate commercial-scale production of Tc-99m from Mo-100 using cyclotron-based systems include the selection and construction of a suitable target backing plate material, i.e., (i) a material to which Mo-100 will adhere strongly prior to and during proton irradiation, (ii) a material that is impermeable to protons, (iii) a material that is mechanically robust enough to withstand heating during proton irradiation, (iv) a material that is thin enough to allow for heat dissipation and / or cooling of the Mo-100 during irradiation, and (iv) a material that is chemically inert, i.e., that does not chemically contaminate or otherwise interfere with the dissolution of the irradiated Mo-100.

[0011] Accordingly, certain exemplary embodiments of the present disclosure relate to a process for purifying commercially available Mo-100 powder into uniform particles of less than 10 microns, a mechanically robust target plate for mounting the purified Mo-100 particles, and an electrophoretic method for mounting the purified Mo-100 particles to the target plate.

[0012] According to one embodiment, commercial grade Mo-100 metal powder is first oxidized in a solution containing about 3% to about 40% hydrogen peroxide (H2O2). A particularly suitable concentration of H2O2 is about 30%. The mixture of Mo-100 and H2O2 is then heated at about 40°C to 50°C to denature the residual H2O2, and then dried to recover solid molybdenum oxide. The solid molybdenum oxide is converted back to Mo-100 metal using a three-stage heating process. In the first stage, the dried molybdenum oxide is heated to about 400°C for about 30 minutes in an environment containing about 2% hydrogen in argon gas mixture to form MoO3. After 30 minutes at 400°C, the temperature is increased to about 700°C for about 30 minutes for the second stage of the process to promote the reduction of MoO3 to MoO2. The temperature is then further increased to about 1100°C for about 30 minutes for the third stage of the process to reduce MoO2 to Mo-100 metal. Since MoO2 sublimes at 1500°C, it is important to maintain the temperature at about 1100°C to about 1455°C, about 1100°C to about 1400°C, about 1100°C to about 1350°C, about 1100°C to about 1300°C, about 1100°C to about 1250°C, or about 1100°C to about 1200°C during the third stage. During the first stage of the process, it is important to limit the atmospheric hydrogen content to less than about 5%, less than about 4%, less than about 3%, and preferably less than about 2% to control the reduction rate of MoO3 to MoO2. Since the reduction of MoO2 to Mo-100 is an endothermic reaction, it is appropriate to use a high hydrogen atmosphere or a pure hydrogen atmosphere for the third stage of the process. The engineered Mo-100 powder produced by this third stage process is characterized by a consistent particle size of less than 10 microns.

[0013] Another aspect of this embodiment of the present disclosure relates to an electrophoretic process for coating a target backing plate with purified Mo-100 powder having a uniform particle size of less than 10 microns. The purified Mo-100 powder is suspended in a suitable polar organic solvent, exemplified by anhydrous nitromethane, nitroalkane, isopropanol, etc., and a suitable binder, exemplified by zein, and then vigorously stirred at an ambient temperature selected from about 15°C to about 30°C. Then, a cathode containing a transition metal and an anode containing a conductive metal, exemplified by copper, are immersed in the suspension. A potential of about 150V to about 5000V, about 200V to about 4000V, about 250V to about 3000V, about 300V to about 2500V, about 400V to about 2000V, or about 500V to about 1500V is applied across the anode and cathode for about 2 minutes to about 30 minutes to deposit Mo-100 and the binder on the cathode. A particularly suitable potential applied across the anode and cathode is about 1200 V. The coated cathode is then removed from the mixture and sintered by heating in an oxygen-free atmosphere provided by an inert gas, such as argon, at a temperature of about 1500°C to about 2000°C, about 1300°C to about 1900°C, about 1400°C to about 1800°C, or about 1400°C to about 1700°C for 2 to 7 hours, 2 to 6 hours, or 4 to 5 hours. We have found that this process allows a molybdenum metal layer to be deposited on a target backing plate (hereinafter also referred to as a "target plate") at a density of about 85% of the theoretical density possible.

[0014] Another aspect of this embodiment relates to a target plate on which Mo-100 can be attached. The target plate configuration is suitable for irradiation with protons delivered by (i) a beamline extending from a cyclotron, or without a beamline, or alternatively (ii) in a self-shielded cyclotron chamber without a beamline. The width of the target plate is sufficient to receive the entire beam spot of proton energy generated with the cyclotron even when delivered to the target plate at a selected angle of about 7° to about 90° with respect to the incident beam. The beam spot typically produced in a cyclotron beamline is collimated with a diameter of about 15 mm. It is common to place the Mo-100 coated target plate at an angle to the protein beamline, in which case the irradiation surface area of ​​the target plate is an elongated spot of about 10 mm to about 15 mm by about 20 mm to about 80 mm. In a self-shielded cyclotron without a beamline, the space for placing the target plate is typically about 30 cm x 30 cm x 30 cm to about 30 cm x 30 cm x 80 cm. Therefore, for large-scale production of Tc-99m, it is desirable to have a target plate that can be used in (i) cyclotrons that use beamlines, such as those exemplified by the TR PET cyclotrons manufactured by Advanced Cyclotron Systems Inc. (ACSI, Richmond, BC, CA), Best Cyclotron Systems Inc. (Springfield, VA, USA), and IBA Industrial (Louvain-la-Neuve, Belgium), and (ii) self-shielded cyclotrons that do not use beamlines, such as those exemplified by GE's PETtrace® cyclotron system (GE and PETtrace are registered trademarks of General Electric Company, Schenectady, NY, USA). An exemplary target plate can be a circular disk for delivering a proton beam at 90° to the target disk, or alternatively, an elongated plate for delivering a proton beam at an angle less than 90° to the target plate.

[0015] However, a significant problem that occurs during proton irradiation of Mo-100 is the generation of excessive heat. Therefore, it is necessary to coat Mo-100 on a target backing plate that is a good thermal conductor and dissipates heat easily. A problem with the most suitable thermally conductive metal is that it has a relatively low melting point. Therefore, a target backing plate that includes a thermally conductive metal that is electrophoretically coated with Mo-100 may melt during the sintering process disclosed herein, densifying the coated Mo-100 powder and making it sticky. It is known that tantalum has a very high melting point, i.e., a melting point of about 3000° C. or higher. Therefore, tantalum appears to be a preferred metal substrate for target backing plate construction. However, a problem with tantalum is that this transition metal has poor thermal conductivity. Therefore, when using tantalum for the target backing plate, it is necessary to keep the target backing plate as thin as possible in order to provide a thickness sufficient to absorb heat and stop residual protons that may exit the Mo-100 layer without breaking or decomposing, while providing some cooling from the coolant flow directly to and around the back of the target backing plate. Therefore, we have investigated various designs and configurations of tantalum target backing plates for covering Mo-100. One approach is to machine a series of interconnected channels into the back of the tantalum target backing plate, as illustrated in Figures 2 and 3. The coolant flow is directed through the channels during proton irradiation, thus dissipating some of the generated heat. However, we have found that providing channels for coolant flow around the back of the tantalum target backing plate compromises the structural strength of the backing plate, i.e., the backing plate is very flexible and breaks under the stresses of the coolant flow and proton irradiation. Surprisingly, we have found that the sintering process which densifies and adheres the Mo-100 coated tantalum target backing plate also significantly hardens the tantalum substrate, thereby rendering the target backing plate mechanically robust and extremely durable in use during proton irradiation and the simultaneous pressurized circulation of coolant around the back of the target backing plate through provided channels.We have determined that sintered Mo-100 coated target plates with tantalum are robust and structurally stable when irradiated with 16.5 MeV protons at greater than 130 microamps and with 18.5 MeV protons at greater than 300 microamps while maintaining the temperature at or below about 500°C with a pressurized flow of coolant around the back of the target backing plate.

[0016] The mass of Mo-100 required to produce a suitable target depends on the size of the proton beam spot. The target must at least match or exceed the size of the proton beam spot. The density of Mo-100 is approximately 10.2 g / cm 3 Therefore, the mass of Mo-100 required to coat the target plate is approximately "Mo-100 density x target area x required thickness" and is calculated for the type of beamline used, i.e., orthogonal irradiation, or alternatively, proton irradiation delivered at an angle less than 90° to the target plate. Note that the mass of Mo-100 required is not affected by the delivery of protons at an angle to the target, since by changing the angle of the target to the beam only one axis of beam projection is extended, and therefore the required thickness of the coating decreases in the same proportion as the surface area increases.

[0017] Table 1 lists the target thicknesses of molybdenum deposited on a circular target plate for orthogonal irradiation with a proton beam (i.e., approximately 90° to the plate) for each of the three irradiation energies commonly used by cyclotrons. [Table 1]

[0018] Table 2 lists the target thicknesses of molybdenum deposited on an elongated target plate for proton irradiation at different angles relative to the target for each of the three irradiation energies listed in Table 1. [Table 2]

[0019] An exemplary target plate 10 is shown in Figures 2 and 3 and has an elongated shape with rounded ends. Figure 2 is a top view of the exemplary target plate 10. Figure 3(a) is a cross-sectional side view of the target plate 10, and Figure 3(b) is a cross-sectional end view of the target plate 10. The thickness of the target plate 10 is sufficient to stop the entire proton beam at a maximum energy of 19 MeV in the absence of molybdenum. However, due to the high heat generated during proton irradiation, water channels 12 are provided on the underside of the target plate 10 to allow circulation of coolant under the target plate 10 to dissipate excess heat. When coated with Mo-100, the target plate is capable of dissipating 300 μA of 18 MeV protons when delivered to an elliptical beam spot of about 10 mm by about 20 mm at an angle of 10° to the target plate while maintaining the temperature at or below about 500°C.

[0020] This exemplary target plate is approximately 105 mm long, 40 mm wide, and 1.02 mm thick. The cathode or target plate may comprise any transition metal, such as copper, cobalt, iron, nickel, palladium, rhodium, silver, tantalum, tungsten, zinc, and alloys thereof. Copper, silver, rhodium, tantalum, and zinc are particularly suitable. It is noted that if tantalum is used as the target plate material, the sintering process also hardens the tantalum target plate significantly, making the target plate very durable and able to withstand destructive stresses resulting from proton irradiation and / or excessive heat generated during proton irradiation and pressurization by coolant flow around the back of the target plate.

[0021] Another problem that must be addressed during the production of Tc-99m from Mo-100 is to ensure that the Mo-100 coated target plate does not oxidize during and after proton irradiation. Molybdenum oxide has a significant vapor pressure at only a few hundred degrees Celsius, so exposure to high heat and oxygen during proton irradiation will result in the formation of molybdenum oxide, resulting in a reduced conversion efficiency of Mo-100 to Tc-99m.

[0022] Accordingly, some exemplary embodiments of the present disclosure relate to a system including (i) components for mounting and housing a Mo-100 coated target plate, hereinafter referred to as a "target capsule assembly" or "target capsule apparatus," and (ii) components for engaging and disengaging the target capsule assembly from a cyclotron-generated proton irradiation source while maintaining an oxygen-depleted atmosphere around the mounted Mo-100 coated target plate. Thus, the systems and components disclosed herein are configured to provide and maintain an atmospheric environment that is substantially oxygen-free, thereby preventing exposure of the Mo-100 coated target plate to oxygen during proton irradiation. The oxygen-free environment can be provided by applying and maintaining a vacuum during and after irradiation. Alternatively, the environment can be saturated with ultra-high purity inert gas.

[0023] The remainder of the disclosure, which refers to Figures 4-14, relates to the use of exemplary embodiments and aspects of the disclosure to irradiate a Mo-100 coated target plate with protons delivered to the target plate at an angle of less than 90° in a beamline, such as a commercially available PET cyclotron, exemplified by one manufactured by ACSI.

[0024] One aspect relates to a target capsule apparatus for mounting a Mo-100 coated target plate. Another aspect relates to a target capsule pick-up apparatus for remote engagement of the target capsule and for transporting the capsule assembly to and engaging the target station apparatus. Another aspect relates to a target station apparatus with a vacuum chamber for engaging the assembled and engaged target capsule apparatus and the target pick-up apparatus. The target station apparatus is sealingly engageable to a proton source from an accelerator such as exemplified by a cyclotron.

[0025] An exemplary elongated target capsule apparatus for mounting an elongated Mo-100 coated target plate for irradiation with protons delivered at an angle less than 90° by a PET cyclotron, such as that manufactured by ACSI, is shown in Figures 4-6. The exemplary target capsule apparatus 20 comprises a bottom target plate holder 21 and a top cover plate 22 having a plurality of spaced apart holes 23 through which socket head cap screws 24 are inserted and threadedly engaged with the bottom target plate holder 21. The elongated target capsule apparatus 20 has a proximal end 25 for engaging a target capsule pick-up apparatus and a distal end 26 having holes 26a for receiving proton emissions from a suitable accelerator (not shown). The distal end 26 of the target capsule device 20 also has two ports 26b for sealingly engaging a supply of chilled coolant flow, which is directed by a channel 27 and flows through a channel 12 provided in the underside of the target plate 10 in contact with the underside of the target plate 10 (see Figures 3(a) and 3(b)). The upper surface of the bottom target plate holder 21 may be inclined at an angle of about 5° to about 85° with respect to the horizontal. The lower surface of the top cover plate 22 is inclined at a matching angle with respect to the upper surface of the bottom target plate holder 21. The elongated target plate 10 is placed on top of an O-ring 28 which thereby fits into the channel provided in the upper surface of the bottom target plate holder 21. The O-ring 28 also fits into the channel provided in the lower surface of the top cover plate 22. When socket head cap screws 24 are inserted through spaced apart holes 23 and threadedly engaged with bottom target plate holder 21, O-ring 28 tightly sealingly engages elongated target plate 10 between bottom target plate holder 21 and top cover plate 22. The outer diameter of proximal end 25 of target capsule device 20 is configured to engage rollers (not shown) provided for this purpose at the target station and rotate target capsule device 20 to align ports 26a, 26b with the target station to form a vacuum and water seal. The symmetrical configuration of target capsule device 20 allows device 20 to be rotated in either a clockwise or counterclockwise direction. Coolant can enter target capsule device 20 through either port 26b and exit through the opposite port 26b.

[0026] An exemplary target pick-up device 40 is shown in Figures 7-8. The target pick-up device 40 includes a pick-up head device 41 configured to engage and disengage from a chamber 25a provided therefor at the proximal end 25 of the target capsule device 20 shown in Figures 4-6. The pick-up head device 41 has a structure that extends and retracts radially from within the pick-up head configured to engage and disengage from the chamber 25a at the proximal end 25 of the target capsule device 20. Suitable engagement devices include pins, prongs, struts, and the like. Figure 8 shows an extendable / retractable prong 43. The target pick-up device 40 also includes a target capsule device pusher 44 that is engageable and disengageable from an engagement device exemplified by the prong 43. The extendable / retractable prong 43 provided on the pick-up head device 41 is actuated and manipulated by a remotely controllable pull ring 49 attached to a coupling shaft 48 extending rearwardly from the pick-up head device 41. The target pick-up device 40 further comprises a target pick-up guide 46 with a forwardly extending shaft 47 which is slidably received and engages a mating shaft 48 extending rearwardly from the pick-up head device 41. The rear of the target pick-up guide 46 cooperates with an engageable / disengageable steel strip (shown in dashed lines in FIG. 8 as shaft 50) which cooperates with the target pick-up device 40 to deliver the target capsule device 20 from the target station receiving cell apparatus 80 (see FIG. 9) to the target station apparatus (shown as item 58 in FIG. 12) and then retrieve the target capsule assembly 20 from the target station apparatus 58 after irradiation and deliver it back to the target station receiving cell apparatus 80.

[0027] 9-11 show an exemplary target station receiving cell apparatus 80 that can be mounted to a lead-lined fume hood. Suitable lead-lined fume hoods include the "Hot Cell" commercially available from Von Gahlen International Inc. (Chatsworth, GA, USA) and Comecer Inc. (Miami, FL, USA). The target station receiving cell apparatus 80 includes a framework 82 to which an upper shelf 83 and a lower shelf 84 are mounted. A drive unit assembly 85 is mounted to the upper shelf 83. The drive unit assembly 85 houses a length of steel strip 50 wound on a drum (not shown) housed within the drive unit assembly 85. A proximal end of the steel strip 50 engages the drum (not shown) provided within the drive unit assembly 85, and a distal end of the steel strip 50 is coupled to the target pick-up apparatus 40 as shown in FIG. The drive assembly includes (i) a first one-way clutch and gear assembly 81 engaged to the drum, (ii) a second one-way clutch and gear assembly 86 controllably engageable with the strip extending therethrough, and (iii) a drive motor 99 that cooperates with a chain (not shown) to provide drive to the first one-way clutch and gear assembly 81 and the second one-way clutch and gear assembly 86. The distal end of the strip is coupled to a pick-up head device 41 of the target pick-up device 40, which extends downwardly within the target guide tube 95 when not in use. The target pick-up device 40 is deployed and retrieved through the target guide tube 95 by operation of the drive unit assembly 85. A gate valve assembly 100 is attached to a port of the hot cell (not shown) directly below the target guide tube 95. A gate valve (not shown) in the gate valve assembly 100 is opened and closed by an actuator 101. Attached to the lower shelf 84 is a carriage rail 115 on which a docking station carriage table 114 is carried back and forth. A docking station 110 is attached to the docking station carriage table 114. The docking station 110 is movable laterally by a pair of linear actuators 116. The docking station includes a housing having three aligned holes 111, 112, 113.Hole 111 is a through hole for connecting the lower end of the target guide tube 95 to the top of the gate valve assembly 100. Hole 112 is provided to receive and store the target capsule device pusher 44 components of the target pick-up device 40 when not in use. Hole 113 is provided to receive the assembled target capsule assembly 20 with the proximal end 25 in the upper position.

[0028] In use, the Mo-100 coated target plate 10 is mounted in the target capsule assembly 20 in the hot cell using a remote control device (not shown). The loaded target capsule assembly 20 is placed in the target capsule assembly receiving hole 113 by the remote controlled device, and the target docking station carriage table 114 is remotely controlled to position in front of and away from the upper shelf 83. The target docking station carriage table 114 is then remotely driven to a position below the upper shelf 83 so that the aligned holes 111, 112, 113 are centrally aligned with the gate valve assembly 100. The docking station 110 is then transported sideways to precisely position the hole 113 below the target guide tube 95, which is simultaneously directed above the gate valve assembly 100. The transport drive unit assembly 85 is then operated to fully deploy the steel strip so that the target pick-up mechanism 41 engages the target capsule device 20, and then the transport drive unit assembly 85 is reversed to pull the target capsule device 20 into the target guide tube 95. The docking station 110 is then moved to align the hole 111 with the target guide tube 95 so that the target guide tube 95 is simultaneously positioned directly above the gate valve assembly 100, and then the actuator 101 is operated to open the gate valve. The release actuator 96 is operated to release the target capsule 20 from the target pick-up mechanism 41, so that the target capsule 20 can fall through the hole in the gate valve assembly 100 into the transport tube 68. The docking station 110 is then moved so that the target capsule pusher receiving hole 112 is directly below the target guide tube 95. The pinch roller 104, in cooperation with the pinch roller linear actuator 103, the pinch roller cam interlock 105, the second one-way clutch and the gear assembly 86, deploys the steel strip from the drum within the transport drive 85, thereby operating the transport drive 85 to engage the target capsule device pusher 44, such that the prongs 43 of the pick-up head device 41 of the target pick-up device 40 engage the target capsule device pusher 44.The first one-way clutch and gear assembly 81 is disengaged and is free to move when the second one-way clutch and gear assembly is engaged. The pinch roller 104 is then disengaged by operating the pinch roller linear actuator 103 in cooperation with the pinch roller cam linkage 15, and the target pick-up device 40 engaged with the pusher 44 is then pulled up into the target guide tube 95 by rewinding the strip on the drum of the transfer drive device 85 having the first one-way clutch and gear assembly 81 in cooperation with the drive motor 99. The second one-way clutch and gear assembly 86 is disengaged and free to move during this operation. The docking station 110 is then moved so that the hole 111 is directly under the target guide tube 95. The transfer drive 85 is then operated to spread the steel strip by the pinch roller 104 in cooperation with the pinch roller linear actuator 103 and the second one-way clutch 86 (the first one-way clutch and gear assembly 81 are disengaged and free to move), and the target pick-up device 40 having a pusher 44 pushes the target capsule assembly 20 through the transfer tube 68 to deliver the target capsule assembly 20 to a target station assembly (shown at 58 in Figures 12-14) which is operably coupled to the cyclotron.

[0029] 12-14 show an exemplary target station apparatus 60 assembly 58 coupled by a spigot flange 66 to a vacuum chamber apparatus 70 that engages a beamline for an accelerator such as a cyclotron (not shown). The assembly is mounted to the facility by a framework 59. The target station apparatus 60 is connected by a transfer tube mount 69 to a transfer tube 68. The other end of the transfer tube 68 engages a flange 120 of a gate valve assembly 100 mounted in a receiving cell apparatus 80 shown in FIGS. 9-11. The target station apparatus 60 comprises a housing into which an elongated target capsule apparatus 20 (shown in FIGS. 4-6) is delivered by a target pick-up apparatus 40 shown in FIGS. 7-8. A linear drive unit 65 mounted on the target station apparatus 60 engages two rollers (not shown). These rollers contact the outer diameter of the proximal end of the target capsule assembly 20 and cooperate with a curved surface of the outer diameter to rotate the target capsule apparatus 20 into alignment with the spigot flange 66. Once aligned, the target capsule device 20 is moved by the linear drive unit 65 into sealing engagement with the spigot flange 66, forming a vacuum-tight connection between the target capsule port 26a and the vacuum chamber device 70, and two water-tight connections with the target capsule port 26b. The target capsule assembly 20 can engage the spigot flange 66 in either of two positions 180° apart, since both positions are operationally identical. The loaded target capsule assembly 20 is ready for proton irradiation. The vacuum chamber 70 is evacuated by a suitable vacuum pump (not shown) interconnected to the vacuum port 73. The proton beam is collimated during the irradiation process by four proton beam collimator assemblies 71 mounted around the vacuum chamber 70. The passage of the proton beam is restricted by baffles 72 to positions where the protons are only incident on the collimator or the target plate 10 of the target capsule assembly 20.

[0030] After the proton irradiation is completed, the beamline is separated from the vacuum chamber 70 with the vacuum valve, and the vacuum chamber pressure is increased to atmospheric pressure. Cooling water is removed from the target capsule 20. The irradiated target capsule assembly 20 is retrieved by engaging the pick-up head device 41 of the target pick-up device 40 with the chamber 25a at the proximal end of the target capsule assembly 20 after being disengaged from the spigot flange 66 by the linear actuator 65. The target capsule assembly 20 is then delivered back to the target station receiving cell device 80 by retrieving the unfolded steel strip 50 by the drive unit assembly 85 until the target capsule unit exits the transfer tube 68 and goes out of the gate valve assembly 100. The docking station 110 is then transported so as to be accurately positioned in the lower hole 113 of the target guide tube 95, and the irradiated target capsule assembly 20 is placed in the target capsule assembly receiving hole 113 and disengaged from the target pick-up device 40. The target pick-up device 40 is then retracted into the target guide tube 95 and the docking station 110 returns to its parked position. As will be described in more detail below, the pertechnetate and molybdate ions are thereby dissolved from the irradiation target plate in an apparatus provided within the hot cell and subsequently recovered and separately purified.

[0031] Another embodiment of the present disclosure relates to a system that includes components for mounting and housing a circular Mo-100 coated target plate, and components for engaging and disengaging the housed circular target plate from a cyclotron generated proton irradiation source while maintaining an oxygen depleted atmosphere around the mounted Mo-100 coated target plate.

[0032] An exemplary circular target plate 140 is shown in Figures 15(a)-15(c). Figure 15(a) is a perspective view from the top of the circular target plate 140, showing a recess 145 around the center of the circular target plate 140. Figure 15(b) is a top view of the circular target plate 140, and Figure 15(c) is a cross-sectional side view of the circular target plate 140. The circular target plate 140 may comprise any transition metal, such as those exemplified by copper, cobalt, iron, nickel, palladium, rhodium, silver, tantalum, tungsten, zinc, and alloys thereof. Copper, silver, rhodium, tantalum, and zinc are particularly suitable. The recess 145 is provided to receive refined Mo-100 metal powder, which is then sintered as previously described.

[0033] 16-18 show an exemplary capsule apparatus 200 for positioning and mounting a Mo-100 coated circular target plate 199 without recesses, or alternatively, a circular target plate with recesses as illustrated in FIGS. 15(a)-a5(c). FIG. 16 is a perspective view, FIG. 17 is an end view with the target plate 140 removed, and FIG. 17 is a cross-sectional side view of the capsule apparatus 200 generally including an outer housing 205, an inner cooling sprinkler 215 (also referred to as a cooling sleeve) for receiving and holding the Mo-100 coated circular target plate 199, and a housing fastening nut 210 for securely engaging the cooling sleeve and the circular target plate 140. An O-ring 219 is inserted between the target plate 199, the outer housing 205, the inner cooling sprinkler 215, and the housing fastening nut 210 to sealingly secure the target plate 199 within the capsule apparatus 200. The purpose of the cooling sleeve 215 is to minimize the possibility of heat-generated oxidation of the molybdenum and technetium atoms by controllably dissipating heat generated by proton irradiation of the Mo-100 coated target plate 140. The capsule housing fastening nut 210 includes a chamber 212 configured to engage and disengage the target pick-up device (item 220 in FIG. 19).

[0034] Another aspect of this embodiment relates to an exemplary target capsule pick-up device 220 for engaging and manipulating an assembled circular target plate capsule device (FIGS. 19-20). FIG. 19 is a perspective view and FIG. 20 is a cross-sectional side view of the target capsule pick-up device 220 engaged with a pusher 225. The target capsule pick-up device 220 generally comprises a radially extendable / retractable pick-up head device 223 for engaging an assembled target plate capsule device 200 or a pusher 225, and a shaft 226 extending rearward from the pick-up head for engaging a shaft 231 extending forward from a target pick-up guide 230. The shaft 231 extends rearward through the target pick-up guide 230 and engages a steel strip 232. The target capsule pick-up device 220 further comprises a target housing pusher 225 for delivering the target capsule device 200 to a target station device (shown in FIGS. 24-27). A shaft 226 extending rearwardly from the pick head device 223 includes an actuation device 227 for radially extending and retracting an engagement device 224 within the pick head device 223 configured to engage and disengage from the assembled target plate housing arrangement. Suitable engagement devices include pins, prongs, struts, etc., which are remotely actuated and manipulated by remote control of the actuation device 227.

[0035] Another aspect of the present embodiment relates to an exemplary target station apparatus for receiving and mounting the assembled circular target plate capsule apparatus to a proton beam port of a cyclotron, as exemplified by GE's PET Trace Cyclotron System. The target station assembly has multiple purposes: (i) receiving and mounting the assembled target plate capsule apparatus to a vacuum chamber, (ii) establishing a stable oxygen-free environment within the vacuum chamber by applying a vacuum and / or replacing ambient air with an ultra-high purity inert gas, as exemplified by helium, (iii) delivering the assembled target plate capsule apparatus to a cyclotron generated proton energy source to engage the target plate capsule apparatus with a proton emission source, (iv) establishing and maintaining a vacuum seal between the target plate capsule apparatus and the proton emission source, (v) precisely manipulating the temperature of the cooling water sprinklers in the housing apparatus during irradiation operations, and (vi) disengaging and removing the irradiated target plate capsule apparatus from the proton emission source.

[0036] 21-24 show another exemplary target station receiving cell apparatus 300 that can be installed in a lead-lined fume hood (also referred to as a hot cell). The receiving cell apparatus 300 includes a framework 305 to which an upper shelf 306 and a lower shelf 307 are attached. A drive unit assembly 310 is attached to the upper shelf 306. The drive unit assembly 310 houses a length of steel strip 232 wound on a drum (not shown) housed within the drive unit assembly 310. The steel strip 232 is deployed and retrieved through a target guide tube 315 interconnected to the drive unit assembly 310 and extending downwardly through the upper shelf 306. A proximal end of the steel strip (232 shown in FIGS. 19-20) engages the drum housed within the drive unit assembly 310 and a distal end of the steel strip 232 is coupled to a target pick-up apparatus 220 as shown in FIGS. 19-20. The drive assembly 310 includes (i) a first one-way clutch and gear assembly 311 that engages the drum, (ii) a second one-way clutch and gear assembly 312 that is controllably engageable with the steel strip extending therethrough, and (iii) a drive motor 313 that cooperates with a chain (not shown) to provide a driving force to the first one-way clutch and gear assembly 311 and the second one-way clutch and gear assembly 312. Thus, the pick-up head device 223 of the target pick-up apparatus 220 extends downwardly together with the target guide tube 315 when not in use. The gate valve assembly 325 is mounted to a port of the hot cell (not shown) directly below the target guide tube 315. The gate valve assembly 325 has a flange 327 for engaging a transfer tube (shown as item 267 in FIG. 24) that operably interconnects with the target station 250 (FIG. 24). A gate valve (not shown) in the gate valve assembly 325 is opened and closed by an actuator 326. Attached to the lower shelf 307 is a carriage rail 340 on which a docking station carriage table 328 is carried back and forth. A docking station 330 is attached to the docking station carriage table 328. The docking station can also be precisely positioned laterally by a pair of linear transducers 341.The docking station 330 comprises a housing having four aligned holes 332, 334, 336, 338. Hole 332 is a through hole connecting the target guide tube 315 to the top of the gate valve assembly 325. Hole 334 is provided to receive and store the target capsule device pusher 225 component of the target pick-up device 220 when not in use. Hole 336 is provided to receive the assembled target capsule assembly 200 with the proximal end 212 in the up position. Hole 338 is provided to receive the irradiated target capsule assembly 200 to dissolve the molybdate and pertechnetate ions from the irradiated circular target plate 140.

[0037] In use, the Mo-100 coated target plate 140 is mounted in the target capsule assembly 200 in a hot cell using a remote controlled device (not shown). The loaded target capsule assembly 200 is placed in the target capsule assembly receiving hole 336 by the remote controlled device, and the docking station carriage table 328 is remotely controlled to position in front of and away from the upper shelf 306. The docking station carriage table 328 is then remotely driven to a position below the upper shelf 306 so that the aligned holes 332, 334, 336, 338 are centrally aligned with the gate valve assembly 325. The docking station 330 is then transported laterally to precisely position the hole 336 below the target guide tube 315, which is simultaneously positioned above the gate valve assembly 325. The transport drive unit assembly 310 is then operated to fully deploy the steel strip to engage the target pick-up mechanism 220 with the target capsule device 200, and then the transport drive unit assembly 310 is reversed to pull the target capsule device 200 into the target guide tube 315. The docking station 330 is moved to align the hole 332 with the target guide tube 315 so that the target guide tube 315 is simultaneously directly above the gate valve assembly 325, and then the actuator 326 is operated to open the gate valve. The release actuator 319 is operated to release the target capsule device 200 from the target pick-up device 220, allowing the target capsule device 200 to drop through the hole in the gate valve assembly 325 into the transport tube 267. The docking station 330 is then moved so that the target capsule pusher receiving hole 334 is directly below the target guide tube 315.The pinch roller 318, in cooperation with the pinch roller linear actuator 316, the pinch roller cam interlock 317, and the second one-way clutch and gear assembly 312 (the first one-way clutch and gear assembly 311 is free to move (i.e., no transport force)), operates the transport drive unit 310 to unfold the steel strip from the drum within the transport drive unit 310, thereby engaging the target pick-up mechanism 220 with the target capsule device pusher 225, such that the prongs 224 of the pick-up head device 223 of the target pick-up device 220 engage the target capsule device pusher 225. The target pick-up device 220 engaged with the pusher 225 is then raised into the target guide tube 315 by first disengaging the pinch roller 318 by operating the pinch roller linear actuator 316 in cooperation with the pinch roller cam linkage 317, and then rewinding the strip onto the drum of the transfer drive 310 having a first one-way clutch and gear assembly 311 (the second one-way clutch and gear assembly 312 is free to move (i.e., no transfer force)) in cooperation with the drive motor 313. The docking station 330 is then moved so that the hole 332 is directly under the target guide tube 95. The transfer drive 315 is then operated to spread the steel strip by the pinch roller 318 in cooperation with the pinch roller linear actuator 316, the cam interlock 317, and the second one-way clutch 312 (the first one-way clutch and gear assembly 311 is free to move (i.e., no transfer force)), and the target pick-up device 220 having a pusher 225 pushes the target capsule assembly 200 through the transfer tube 267 to deliver the target capsule assembly 200 to a target station assembly (shown at 270 in Figures 24-27) that is operably coupled to the cyclotron.

[0038] 24-27 show a target station assembly 250 with an exemplary target station housing 252 for receiving a target capsule device 200 delivered by a target pick-up device 220, which is then mounted in a loading position within the target station housing 252 (FIG. 27). The target station assembly 250 is mounted to a PET Trace® cyclotron (not shown) by a framework 251. The target station housing 252 is engaged to a cylindrical support element 256 to which a first pneumatic drive cylinder 270 is interconnected. The target station housing 252 includes a receiving chamber 253 (best seen in FIG. 27) and an irradiation chamber 254 (best seen in FIG. 26) with a port 259 for engaging a cyclotron proton ejection port (not shown). The receiving chamber 253 is connected to a transfer tube 267 through which the target capsule device 200 is delivered by the target pick-up device 220. The target capsule device 200 is moved from the receiving chamber 253 to the irradiation chamber 254 within the target station housing 252 by a target holder device 255 interconnected with a second pneumatic drive cylinder 272. The target holder device 255 is operatively connected to a limit switch 262 (FIG. 25) for remote detection of the target capsule device 200. Upon entering the irradiation chamber 254, the target capsule device 200 is sealingly engaged with the front flange 261 of the target housing by a first pneumatic drive cylinder 270. A cylindrical support element target 256 includes a cooling tube assembly 257 which, upon placement in the irradiation chamber 254, is moved into the target capsule device 220 by the first pneumatic drive cylinder, simultaneously pressing the target capsule device against the front flange 261 of the target housing to form a vacuum-tight seal. The port 259 thus sealingly engages the cyclotron, thereby forming a vacuum chamber adjacent to the cyclotron and allowing free passage of energetic protons to the target plate 140 / 199. The cooling tube assembly 257 engages the cooling water distribution sleeve 215 of the target capsule assembly to deliver cooling fluid through the passageway 218 .After being placed in the target station irradiation chamber 254, the loaded target capsule assembly 200 is ready for proton irradiation. After completion of proton irradiation, cooling fluid is removed from the cooling tube assembly 257 and the cooling tube assembly is extracted from the cooling water spray sleeve 215 by the first pneumatic drive cylinder 270. The irradiated target capsule assembly 200 is removed from the irradiation chamber 254 to the receiving chamber 253 of the target station housing 252 by the operation of the second pneumatic drive cylinder 272. The irradiated target capsule assembly 200 is then retrieved from the target station assembly 250 by engaging the pick-up head device 223 of the target pick-up device 220 with the chamber 212 at the proximal end of the target capsule assembly 200 in cooperation with the landing pad device 258 and the limit switch 262. The target capsule assembly 200 is then delivered back to the receiving cell device 300 by retrieving the steel strip 232 deployed on the drum provided on the drive unit assembly 310 by the engagement of the first one-way clutch and gear assembly 311 before the target capsule unit 200 exits the transfer tube 267 and exits the gate valve assembly 325. The docking station 330 is then transported to accurately position the target plate lysis module 338 at the bottom of the target guide tube 315. The drive unit assembly 310 is then operated to push the target capsule assembly 200 into the lysis module 338, thereby forming a liquid-tight seal between the target plate 140 / 199 and the lysis module 338. As will be described in more detail below, the pertechnetate ions and molybdate ions are lysed and retrieved from the irradiated target plate and then purified separately.

[0039] Due to facility design and space configuration limitations, some cyclotron facilities may need to place the hot cell in which the exemplary receiving cell apparatus according to the present disclosure is installed at a distance from the target station assembly attached to the cyclotron to which the receiving cell apparatus is connected by a transfer tube. As the length and number of bends of the transfer tube required to travel the distance between the receiving cell apparatus and the target station assembly increases, the stress and strain on the drive unit assembly and the steel strip parts of the receiving cell apparatus used to deliver and retrieve the target capsule assembly to and from the target station assembly also increases. Therefore, another embodiment of the present disclosure relates to a booster station apparatus that can be installed in the transfer tube located between the receiving cell apparatus and the target station assembly. An exemplary booster station apparatus 400 is shown in FIG. 28-FIG. 29 and generally comprises a booster station framework 415 and a booster station housing 410. The booster station framework 415 includes a transfer tube support plate 425 having an orifice through which a first transfer tube (not shown) is inserted, a booster housing back plate 420, and a framework stabilizer plate 427 having one end that engages the transfer tube support plate 425 and the other end that engages the booster housing back plate 420. The booster station apparatus includes a flange 422 (best seen in FIG. 29) having an orifice for engaging an end of the first transfer tube. The housing 410 includes a flange 430 and an orifice 412 that aligns with the orifice in the flange 422. The orifice 412 in the housing 410 allows a second transfer tube (not shown) to be inserted. The second transfer tube is engaged with the orifice in the flange 430. The pinch roller assembly with extendable / retractable framework includes a pair of pivotable upper mounting assemblies 445 to which the upper rollers 440 are mounted, a pair of pivotable lower mounting assemblies 455 to which the lower rollers 450 are mounted, and a flange 430 connecting the left pair of pivotable upper mounting assemblies 445 and pivotable lower mounting assemblies 455 to a corresponding right pair of pivotable upper mounting assemblies and pivotable lower mounting assemblies (not shown).A pair of actuators 460 are attached to the booster station framework 415 for extending and retracting the pinch roller assemblies 445, 455, 430. A drive unit 465 is attached to the pinch roller assemblies 445, 455, 430 for rotating the upper roller 440 when the pinch roller assemblies 445, 455, 430 are extended. When the pinch roller assemblies 445, 455, 430 are in the retracted position as shown in Figure 28, the upper roller 440 and the lower roller 450 are positioned further apart than the diameter of the target tube to allow the target capsule device and the target pick-up device to pass through the booster station. When the pinch roller assemblies 445, 455, 430 are fully extended as shown in Figure 29, the upper roller 440 and lower roller 450 frictionally engage the top and bottom surfaces of the strip and apply a motive force provided by the drive unit 465 to assist in delivery of the target capsule device to the target station assembly engaged to the cyclotron, or to a receiving cell depending on the direction of rotation of the drive unit 465. The amount of friction provided is adjusted by air pressure applied to the linear actuator 460.

[0040] Another exemplary aspect of this embodiment of the present disclosure relates to a process for dissolving and recovering molybdate and pertechnetate ions from a proton irradiated target plate, and then separating and separately purifying the molybdate and pertechnetate ions by contacting the exposed surface of the proton irradiated target plate with a recirculating solution of about 3% to about 30% H2O2 for about 2 minutes to about 30 minutes to purify the target plate. The oxide solution is formed by dissolving the molybdate and pertechnetate ions from the surface of the target plate. The peroxide solution may be recirculated. For example, the peroxide solution may be heated by heating the dissolution chamber 338 with a heater cartridge disposed in the chamber body. After the oxide solution is collected, the dissolution system and target plate are rinsed with deionized distilled water. The rinse / clean water is added to the oxide solution and mixed. The pH of the collected oxide / rinse solution is then adjusted to about 14 by mixing about 1N to about 10N KOH or about 1N to about 10N NaOH. The pH adjusted oxide / rinse solution may then be heated to about 80° C. for about 2 minutes to about 30 minutes to decompose any residual H2O2 in the pH adjusted oxide / rinse solution. The strongly basic pH of the oxide / rinse solution maintains the molybdenum and technetium species as K2[MoO4] or Na2[MoO4] and K[TcO4] or Na[TcO4] ions, respectively, or in forms such as Mo2(OH)(OOH), H2Mo2O3(O2)4, H2MoO2(O2), etc.

[0041] The pH adjusted (and optionally heated) oxide / rinse solution is then forced through a solid phase extraction (SPE) column packed with a commercial resin exemplified by DOWEX® IX8, ABEC-2000, AniligTc-02, etc. (Dowex is a registered trademark of Dow Chemical Co., Midland, MI, USA). The pertechnetate ions are immobilized on the resin beads, and the molybdate ions in solution pass through and exit the SPE column. The molybdate ion solution is then collected in a reservoir. The SPE column is then rinsed with an appropriate solution to maintain the affinity of pertechnetate for the SPE column, but ensure that molybdate and other impurities are removed. The rinse solution is added to the collected molybdate ion solution. The pertechnetate ions are then eluted from the SPE column using tetrabutylammonium bromide (5-10 mL) in CHCl3 (0.1-1.0 mg / mL). Alternatively, the pertechnetate ion may be eluted from the SPE column with NaI (0.1-1.0 mg / mL).

[0042] The pertechnetate ion solution eluted from the SPE column is forced through an alumina column preceded by a suitable column to remove eluted components. For Dower® / ABEC, the alumina column is preceded by a cation exchange SPE cartridge to remove residual base from the eluent. The alumina column may also be preceded by an SPE cartridge to remove iodide from the eluent and immobilize pertechnetate on the alumina. Using NaI to remove TcO4 is optional, in which case an Ag / AgCl SPE cartridge is required in the form of an alumina column. The adsorbed pertechnetate ion is washed with water and then eluted through a 0.2 micron filter with saline containing 0.9% NaCl (w / v) and collected in a lead-shielded container vial. The eluent from the alumina column contains sterile Na[TcO4] free of impurities.

[0043] The molybdate ions / rinse solution collected from the SPA column is dried. Suitable drying methods include freeze-drying. The resulting powder can be suspended in about 3% to about 35% NaOH solution or about 3% to about 35% KOH solution, and the solution can be filtered and dried. The resulting powder can be solubilized in distilled water and dried again to obtain a clean Na2MoO4 or K2MoO4 product. The Na2MoO4 or K2MoO4 is then forced through a strong acid cation exchange column to allow for the recovery and elution of H2[MoO4] and other polymeric oxide species of molybdenum, exemplified by heptamolybdate and octamolybdate. The eluted molybdenum oxide is then frozen, dried, and stored. The dried molybdenum oxide powder thus recovered and stored can be reduced for coating on new target plates as described above.

[0044] Accordingly, another exemplary embodiment of the present disclosure relates to a system and apparatus, also collectively referred to as a lysis / purification module, engageable and operable with the exemplary receiving cell apparatus disclosed herein for receiving and mounting an irradiated Mo-100 coated target plate for the lysis, recovery and purification of molybdate and pertechnetate ions. The exemplary lysis / purification module of the disclosed embodiment generally comprises: (i) a sealable container for indirectly mounting an irradiated Mo-100 coated target plate (also referred to as a "melting chamber"); (ii) a recirculating supply of H2O2 solution comprising a reservoir, a conduit structure interconnecting the reservoir and the dissolution vessel, a pump for recirculating the H2O2 solution, an inlet port for introducing fresh H2O2 solution, an outlet port for controllably removing a portion of the recirculating H2O2 solution, and instruments for monitoring the activity, temperature, flow rate, etc., of the recirculating H2O2 solution; (iii) a supply of distilled water interconnected to the dissolution vessel for post-dissolution cleaning of the dissolution vessel and a recirculating supply of H2O2 solution; (iv) a chemical processing station having a plurality of ports for individually engaging disposable resin cartridges for immobilizing and mobilizing pertechnetate and molybdate ions, a conduit structure for separately collecting the pertechnetate ions, molybdate ions, and wash waste water from the resin cartridges, and a filling / capping station for capturing and storing the collected pertechnetate ions, molybdate ions, and wash waste water.

Claims

1. A target plate for producing technetium-99m from molybdenum-100 by irradiating it with protons, comprising: a bottom surface having a channel for receiving a flow of coolant therethrough; an upper surface comprising tantalum for receiving Molybdenum 100 powder, the upper surface being coated by electrophoresis and sintering of Molybdenum 100 powder; A target plate comprising:

2. a bottom target plate holder having an inclined surface for mounting the target plate, the bottom target plate holder including: (i) a port for communicating a flow of coolant; (ii) a first flow passage for directing the coolant to a bottom of the target plate; and (iii) a second flow passage for directing the coolant away from the bottom of the target plate; a top cover plate that is sealably removable with respect to the bottom target plate holder, the top cover plate having a port for communicating a flow of coolant, and a third flow passage in communication with the second flow passage of the bottom target plate holder for directing the coolant flow away from the bottom of the target plate.

2. A target capsule device for receiving and housing therein a target plate as described in claim 1, having a distal end with a hole for receiving proton emissions from a suitable accelerator and a proximal end for engaging a target capsule pick-up device, the number of ports being two.

3. A target capsule pick-up device for releasably engaging the proximal end of a target capsule device according to claim 2 to deliver the target capsule device to a target station device.

4. a target guide tube for receiving the target capsule assembly therein; a drive unit assembly for deploying and retrieving the targeting capsule assembly; a gate valve assembly located between the target guide tube and the drive unit assembly; a docking station carriage table having a docking station mounted thereon; a carriage rail for carrying the docking station carriage table; A target station receiving cell apparatus for receiving therein a target capsule apparatus as described in claim 2 and comprising: a linear actuator for transporting said docking station carriage table along said carriage rail.

5. A target station apparatus for receiving therein a target capsule apparatus as described in claim 2, comprising a roller assembly that sealably engages a vacuum chamber that engages a beam line for an accelerator for irradiating the target plate with protons, and for transporting and positioning the target capsule apparatus within the vacuum chamber.

Images