Dual-radionuclide production target and processing system

Abstract

A dual-radionuclide production target includes a first radionuclide target that produces a first radionuclide when irradiated by a particle beam from a radionuclide production system, and a second radionuclide target that produces a second radionuclide when irradiated by the particle beam that has passed through, and been degraded by, the first radionuclide target. With this design, the first radionuclide target serves two purposes: it reduces the beam energy to a suitable energy for isotope production on the second radionuclide target, and in-doing so becomes activated with a medically relevant radionuclide that can be easily extracted. In this way, in a single production run can produce two or more radionuclides.

Description

Mayo 2024-254 Q&B Docket: 630666.01614 DUAL-RADIONUCLIDE PRODUCTION TARGET AND PROCESSING SYSTEM CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No.63 / 685,247, filed on August 20, 2024, and entitled “Dual-radionuclide Production Target and Processing System,” which is herein incorporated by reference in its entirety. BACKGROUND

[0002] Typically, medical cyclotrons used for radionuclide production generate fixed energy beams at a set point between 10–30 MeV. Beam degraders composed of blocks or metal foils are used to absorb some of the incident energy from the beam and are tailored such that the exit energy matches the optimal production energy for the desired nuclear reaction to occur on the target, producing the medical radionuclide with minimal by-products. SUMMARY OF THE DISCLOSURE

[0003] It is an aspect of the present disclosure to provide a dual-radionuclide production target that includes a first radionuclide target, a second radionuclide target, and a target body that holds the first radionuclide target and the second radionuclide target in alignment along an irradiation beam axis such that particle beam irradiates the first radionuclide target before irradiating the second radionuclide target. The first radionuclide target is composed of a first material that when irradiated with a particle beam having an energy at a first energy level causes a first radionuclide to form in the first material while degrading the energy of the particle beam to a second energy level. The second radionuclide target is composed of a second material that when irradiated with the particle beam having its energy at the second energy level causes a second radionuclide to form in the second material.

[0004] It is another aspect of the present disclosure to provide a method for producing a plurality of radionuclides in a single production run. The method includes arranging a radionuclide target holder in a beam path of a particle beam source, where the radionuclide target holder holds a first radionuclide target and a second radionuclide target aligned within the beam path. The first radionuclide target is composed of a first material and the second radionuclide target is composed of a second material. The radionuclide target holder is irradiated with a particle beam from the particle beam source such that the particle beam irradiates the first radionuclide target at a first energy level before irradiating the second 1 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 radionuclide target at a second energy level that is lower than the first energy level. Irradiating the first radionuclide target with the particle beam at the first energy level produces a first radionuclide in the first material and degrades an energy of the particle beam from the first energy level to the second energy level. Irradiating the second radionuclide target with the particle beam at the second energy level produces a second radionuclide in the second material.

[0005] It is yet another aspect of the present disclosure to provide a radionuclide processing system to separate two radionuclide products from a dual-radionuclide production target. The radionuclide processing system includes a radionuclide target collection system and a radionuclide processing system. The radionuclide target collection system includes a receptacle and a rotatable tray. The receptacle of the radionuclide target collection system receives a dual-radionuclide production target that has been irradiated by a particle beam, where the dual-radionuclide production target includes a first radionuclide target having formed therein a first radionuclide and a second radionuclide target having formed therein a second radionuclide. The rotatable tray receives the dual-radionuclide production target from the receptacle and rotates the dual-radionuclide production target to a consistent orientation. The radionuclide processing system includes a receptacle to receive the dual-radionuclide production target from the radionuclide target collection system, a first extraction assembly to extract the first radionuclide target from the dual-radionuclide production target, and a second extraction assembly to extract the second radionuclide target from the dual-radionuclide production target. BRIEF DESCRIPTION OF THE DRAWINGS

[0006] FIGS. 1A–1F show examples of a dual-radionuclide production target according to some embodiments described in the present disclosure. FIG. 1A illustrates a schematic of dual-radionuclide target insert with all components taken apart. FIG.1B illustrates a schematic of dual-radionuclide target insert, with target 2 in position for isotope production. FIG.1C illustrates a schematic of dual-radionuclide target insert, with target 2 in position and target 1 in position for isotope production. FIG.1D illustrates a schematic of dual-radionuclide target insert, with cover foil in position for isotope production. FIG. 1E illustrates a cross- section view of dual-radionuclide target insert (view 1). FIG. 1F illustrates another cross- section view of dual-radionuclide target insert. 2 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614

[0007] FIG.2 illustrates one example of a complete target system (e.g., “target system 1”) where the target insert housing isotope production targets 1 and 2 are at 90º to the beamline. (A) Assembled target system 1. (B) Exploded view of complete target system.

[0008] FIG. 3 illustrates another example of a complete target system (i.e., “target system 2”) where the target insert housing isotope production targets 1 and 2 are at 30º to the beamline. (A) Assembled target system 2 (top-view). (B) Assembled target system 2 (top-view, translucent). (C) Assembled target system 2 (side-view). (D) Assembled target system 2 (side- view, translucent).

[0009] FIG.4 illustrates a set-up of a cyclotron beamline and complete target assembly, illustrated with target system 1.

[0010] FIG.5A illustrates an exploded view of a target system highlighting rear water- cooling.

[0011] FIG.5B illustrates a rear water-cooling volume extract.

[0012] FIG. 6A illustrates an exploded view of target system 1 drawing, highlighting the target insert and target holder.

[0013] FIG.6B illustrates an assembled target holder and insert.

[0014] FIG. 6C illustrates a quick release mechanism of target insert from the target holder.

[0015] FIG. 6D illustrates a quick release mechanism of target insert from the target holder (top-view).

[0016] FIG. 7A illustrates a helium cooling component. Helium flow volume (green) is highlighted.

[0017] FIG.7B illustrates a helium cooling flow channel represented through velocity vectors.

[0018] FIG.8A illustrates a front water-cooling component. Water flow volume (blue) is highlighted.

[0019] FIG.8B illustrates a highlighted view of a front water-cooling channel.

[0020] FIG.8C illustrates cyclotron vacuum foil-cooling components.

[0021] FIG.8D illustrates a comparison of cyclotron vacuum foil performance with (i) previously disclosed cooling system and (ii) improved cyclotron vacuum foil cooling set-up with directed helium jet flow at the beam strike area and added water cooling around the perimeter of the beam. The cyclotron vacuum foil is an essential component in cyclotron target assemblies which separates the cyclotron vacuum environment from the rest of the target 3 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 system. This foil is ideally kept as thin as achievable to minimize beam energy degradation. Poor cooling can result in foil rupture and isotope production failure. Improved cooling on this region allows for thinner foils to be used (20 µm instead of 50 µm, for example). Improved cooling also increases the lifespan of the foil, reducing the need for frequent replacement between irradiations which contributes to cyclotron operator dose.

[0022] FIG. 9 illustrates a complete target system 1 picture of complete set-up, connected to the cyclotron beamline.

[0023] FIG. 10 illustrates varying optimal production energy windows of different radionuclides allows combinations to be selected for dual-radionuclide production.

[0024] FIG. 11 illustrates cross-section data for simultaneous production of the67Cu / 64Cu (Target 1 / Target 2) theranostic pair.

[0025] FIG. 12 illustrates cross-section data for simultaneous production of the47Sc / 44Sc (Target 1 / Target 2) theranostic pair.

[0026] FIG. 13 illustrates cross-section data for simultaneous production of the67Ga / 68Ga (Target 1 / Target 2) theranostic pair.

[0027] FIG. 14 illustrates cross-section data for simultaneous production of the55Co / 58mCo (Target 1 / Target 2) theranostic pair.

[0028] FIG.15 illustrates cross-section data for simultaneous production of the123I / 124I (Target 1 / Target 2) theranostic pair.

[0029] FIGS. 16A and 16B illustrate an example radionuclide processing and distribution system in accordance with some embodiments described in the present disclosure.

[0030] FIGS. 17A–17D illustrate an example radionuclide target collection system of the radionuclide processing and distribution system described in the present disclosure.

[0031] FIGS.18A–18C illustrate an example radionuclide target processing system of the radionuclide processing and distribution system described in the present disclosure.

[0032] FIG.19 is an example radionuclide production system.

[0033] FIG. 20 is a flowchart of an example method for producing multiple radionuclides in a single production run using the radionuclide production targets described in the present disclosure.

[0034] FIG. 21A illustrates a comparison of integrity of 0.1 mmnatY foil during 1 hr 40 µA production of89Zr / 44Sc (Target 1 / Target 2) PET radionuclide pair. Enhanced cooling set-up avoided foil rupture during irradiation for scalable production. 4 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614

[0035] FIG.21B illustrates a comparison of integrity of 80 mg pressednatCaO powder during 1 hr 40 µA production of89Zr / 44Sc (Target 1 / Target 2) PET radionuclide pair. Enhanced cooling set-up avoided target fragmentation for scalable production.

[0036] FIG. 22A illustrates an HPGe spectrum of dissolved Target 1 (89Zr) after production of the89Zr / 44Sc (Target 1 / Target 2) PET radionuclide pair. When targets remain intact and physically apart, no cross-contamination is detected.

[0037] FIG. 22B illustrates an HPGe spectrum of dissolved Target 2 (44Sc) after production of the89Zr / 44Sc (Target 1 / Target 2) PET radionuclide pair. When targets remain intact and physically apart, no cross-contamination is detected. DETAILED DESCRIPTION

[0038] Described here are systems and methods for jointly producing two radionuclides in a single radionuclide production run. A dual-radionuclide production target includes a first radionuclide target that produces a first radionuclide when irradiated by a particle beam from a radionuclide production system, and a second radionuclide target that produces a second radionuclide when irradiated by the particle beam that has passed through, and been degraded by, the first radionuclide target. With this design, the first radionuclide target serves two purposes: it reduces the beam energy to a suitable energy for isotope production on the second radionuclide target, and in-doing so becomes activated with a medically relevant radionuclide that can be easily extracted. In this way, in a single production run can produce two or more radionuclides.

[0039] It is an advantage of the present disclosure that using the dual-radionuclide production target allows to produce theranostic pairs (e.g., imaging and therapy) of radionuclides in a single run without cross-contamination. In turn, this process enhances the utility of existing particle accelerators. The disclosed systems and methods can produce radionuclide pairs in different possible combinations (theranostics) considering their needed energy window for an optimal nuclear reaction, without the significant cost of buying and maintaining a second particle accelerator. Additionally, the disclosed systems and methods enable in-house capabilities to simultaneously produce the required radionuclides for research and clinical applications.

[0040] Currently, the energy that is lost in degrading the beam energy to a suitable level for a particular nuclear reaction is truly lost. The disclosed systems and methods capture that otherwise lost energy and repurpose it for a maysecondary radionuclide production, at no 5 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 detriment to the original target. This means that instead of each radionuclide requiring its own production run, resources, and time on the cyclotron (or other accelerator) schedule, two or more radionuclides can be generated in a single production run. When optimized, this has the potential to significantly improve cyclotron scheduling efficiency and increase the radionuclide production capabilities.

[0041] Referring now to FIGS. 1A–1D, an example dual-radionuclide production target 10 is illustrated. The dual-radionuclide production target 10 includes a target body 12 configured to house a first radionuclide target 14 composed of a first material and a second radionuclide target 16 composed of a second material. The first material is a material that activates at a higher energy level than the second material to produce medically relevant radionuclides, whereas the second material is a material that activates at a lower energy level than the first material to produce medically relevant radionuclides. The first radionuclide target 14 and second radionuclide target 16 are retained by the target body 12 such that the first radionuclide target 14 and second radionuclide target 16 are aligned with each other along the beam axis of the radionuclide production system (e.g., along the beam axis of the particle beam generated by the particle accelerator, etc.).

[0042] The target body 12 is configured to retain the first radionuclide target 14 and second radionuclide target 16 such that when in use the first radionuclide target 14 is irradiated by the particle beam before the second radionuclide target 16. That is, the target body 12 holds the first radionuclide target 14 and the second radionuclide target 16 such that the particle beam irradiates the first radionuclide target 14, wherein the particle beam activates the first radionuclide target 14 to produce a first radionuclide before exiting the first radionuclide target 14 and irradiating the second radionuclide target 16, wherein the particle beam activates the second radionuclide target 16 to produce a second radionuclide. In the process of irradiating the first radionuclide target 14, the particle beam is degraded, such that its energy decreases from a first energy level to a second energy level. That is, the particle beam irradiates the first radionuclide target 14 at the first energy level and then irradiates the second radionuclide target 16 at the second energy level.

[0043] The target body 12 generally includes a target backing 18 and a cover foil 20. The cover foil may include an aperture 22 that is sized to at least partially expose the first radionuclide target 14. The target backing 18 has formed therein a first recess 24 for receiving and retaining the first radionuclide target 14 and a second recess 26 for receiving and retaining the second radionuclide target 16. The first recess 24 and the second recess 26 may be nested, 6 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 such that the first radionuclide target 14 and the second radionuclide target 16 are both aligned along the beam axis of the radionuclide production system when the first radionuclide target 14 is retained by the first recess 24 and the second radionuclide target 16 is retained by the second recess 26. The dimensions of the first and second radionuclide targets 14, 16 and the first and second recesses 24, 26 are such that when the first radionuclide target 14 is retained by the first recess 24 and the second radionuclide target 16 is retained by the second recess 26, both the first and second radionuclide targets 14, 16 are physically apart from each other and are thus not in physical contact with each other. This arrangement mitigates potential cross- contamination between the first and second radionuclide targets 14, 16, and also enhances heat dissipation in the first and second radionuclide target 14, 16. In use, the second radionuclide target 16 can be loaded into the second recess 26 before loading the first radionuclide target 14 into the first recess 24.

[0044] FIG. 1A shows a schematic of dual-radionuclide production target 10 with all components taken apart. The target insert 12 includes the target backing 18, cover foil 20, first radionuclide target 14 (i.e., “Target 1”) and second radionuclide target 16 (i.e., “Target 2”). In the illustrated example, the target backing 18 features grooves for insertion of cover foil 20, area 26 for the second radionuclide target 16 and area 24 for the first radionuclide target 14. The cover foil 20 may feature a cut out region 22 so as to not degrade the beam before impinging on the first radionuclide target 14. FIG.1B illustrates the second radionuclide target 16 in position 26 for isotope production. Position 26 has a area that is smaller than position 24, to separate the second radionuclide target 16 from the first radionuclide target 14. FIG. 1C shows the first radionuclide target 14 in position 24 for isotope production. Position 24 has a area that is larger than position 26, to separate the first radionuclide target 14 from the second radionuclide target 16. FIG. 1D shows a schematic of the dual-radionuclide target insert 10 with the second radionuclide target 16 in position 26 and the first radionuclide target 14 in position 24 for isotope production. The cover foil 20 is slid onto target backing 18 through the side grooves 28. FIG. 1E shows a cross-section view of the dual-radionuclide target insert 10 with the first radionuclide target 14 and second radionuclide target 16 in position for isotope production. A physical gap separating the first radionuclide target 14 and the second radionuclide target 16 is created when area 24 is greater than area 26, and the thickness of the second radionuclide target 16 does not exceed the depth of area 26. FIG. 1F shows a cross- section view of the dual-radionuclide target insert 10 for dual-radionuclide production with the first radionuclide target 14 and second radionuclide target 16 in position for isotope production. 7 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 A physical gap separating the first radionuclide target 14 and the second radionuclide target 16 is created when area 24 is greater than area 26, and the thickness of the second radionuclide target 16 does not exceed the depth of area 26.

[0045] Cooling of the target body 12 may be provided by a cooling mechanism integrated with or coupled to the target body. As a non-limiting example, the cooling mechanism may include a liquid cooling mechanism or other fluid cooling mechanism, such as a mechanism that enables direct and / or indirect fluid cooling of the target body 12. The fluid cooling mechanism may be provided by flowing a fluid coolant (e.g., water, helium, liquid nitrogen, etc.) over at least part of the target body 12. In some embodiments, the fluid cooling mechanism may include channels formed in or coupled to the target body, through which a fluid coolant flows. As the fluid coolant flows through the channels, heat is transferred from the target body 12 to the fluid coolant. The heated coolant is then pumped or otherwise flowed to a heat exchanger where the heat may be released to the environment. Additionally, or alternatively, the target body 12 may include a cooling mechanism on the cover foil 20. For example, the cooling mechanism on the cover foil 20 may include fluid cooling provided by helium flow, water cooling, or the like. In some example configurations, the dual-radionuclide production target 10 has cooling mechanisms to cool the target body 12, target backing 18, and / or cover foil 20, as will be described in more detail below.

[0046] FIGS 2A and 2B illustrate an example where the target body 12 is configured for use with a 90-degree beam striking. This configuration of may be referred to as “Target System 1,” or a first configuration of a target system 50. The dual-radionuclide target insert 10 is introduced to the beamline through the complete target system 50 including four primary components: a rear water-cooling assembly 52, a target holder 54 that contains the dual- radionuclide target insert 10, a helium cooling assembly 56, and a front water-cooling assembly 58, which may also include a beamline connection snout 60. These four components are assembled together through the target mount 62, which features four screws of appropriate length to fit the length of the entire target system 50. This simple design enables rapid (e.g., within a minute) assembly and disassembly when required. Rapid assembly and disassembly is advantageous for ease of operation and minimizing cyclotron operator dose.

[0047] FIGS 3A–3D illustrate an example where the target body 12 is configured for use with a 30-degree beam striking. This configuration of may be referred to as “Target System 2,” or a second configuration of a target system 50. The dual-radionuclide target insert 10 is introduced to the beamline through the complete target system 50 including the same 8 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 components described above: a rear water cooling assembly 52, a target holder 54 that contains the dual-radionuclide target insert 10, a helium cooling assembly 56, and a front water cooling assembly 58, which may also include a beamline connection snout 60. These four components are assembled together through the target mount 62, which features four long screws that fit the length of the entire target system 50. In this slanted target configuration, the rear water- cooling assembly 52, target holder 54, and target mount 62 are at 30 degrees to the beamline.

[0048] Referring again to FIGS.1A–1F, the target backing 18 may include a lip 28 on each its lateral sides (e.g., the left and right side of the target backing 18). The lip 28 can receive and retain the cover foil 20. In use, the first and second radionuclide targets 14, 16 are loaded into the first and second recesses 24, 26, respectively, and then the cover foil 20 can be slid into the lips 28 to retain the first and second radionuclide targets 14, 16 in the target backing 18. The target backing may be composed of a suitable material, such as aluminum, copper, tungsten, or the like.

[0049] As shown in FIG. 4, the dual-radionuclide target insert 10 is introduced to the beamline through a target system 50 that includes the target holder 54, front and rear cooling assemblies (58, 52) and the beamline connection snout (60), as described above with respect to FIGS.2A and 2B (Target System 1) or FIGS.3A–3D (Target System 2). The same primary components apply to the first target system (90° to the beamline) and second target system (30° to the beamline).

[0050] FIGS. 5A and 5B illustrate an example rear water-cooling assembly 52. The dual-radionuclide target insert 10 is cooled on its back through the flow of a liquid coolant through the rear water-cooling assembly 52. The liquid coolant may be, for example, chilled water. The flow volume (blue) is designed to increase flow of water directly along the dimensions of the target insert area 26 for enhanced cooling. FIG. 5B shows an example expanded view of the rear water-cooling volume extract.

[0051] FIG.6A shows an exploded view of the target system 50. The target holder 54 includes a back part 542 and a front part 544 that enclose the dual-radionuclide target insert 10 within the target system 50. FIG.6B shows an example of the assembly target holder 54 having a target insert 10 arranged therein.

[0052] As shown in FIGS. 6C and 6D, the target holder 54 is equipped with an electronically controlled release mechanism 64 for rapid, contact free delivery of the dual- radionuclide target insert 10. By operating the release mechanism 64, the dual-radionuclide target insert 10 is released from the target holder 54 and deposited in a target container 66. As 9 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 one example, the release mechanism 64 may include an electromagnetic latch system that uses an electromagnet to hold the front part 544 and back part 542 of the target holder 54 together. When power is removed or reversed, the magnetic field releases, allowing the pieces to separate and the target insert 10 to be released. As another example, a solenoid actuator may be used to retract locking pins or bolts that secure the front part 544 and back part 542 of the target holder 54 together, or that otherwise secure the target insert 10 within the target holder 54. When the solenoid is energized, it may pull the locking elements away from their engaged position, allowing the target insert 10 to be released from the target holder 54. As yet another example, a small electric motor may drive a cam, gear train, or lead screw mechanism to move locking elements out of engagement. The motor may rotate to withdraw locking pins, slide latches, or rotate cam locks that hold the target insert 10 within the target holder 54. Electronically controlled pneumatic valves may also be used to direct compressed air or gas to actuators that operate the release mechanism 64. The pneumatic actuators may push or pull locking elements, or may directly separate the target holder pieces (542, 544) by applying force between them. A spring-loaded mechanism may also be held in the locked position by an electronically controlled latch or brake. When the electronic control releases the latch, spring force may rapidly separate the target holder pieces (542, 544) and eject the target insert 10.

[0053] FIGS. 7A and 7B illustrate an example helium-cooling assembly 56. The helium-cooling assembly 56 is designed for increased flow at the target insert surface (i) and the back of the cyclotron vacuum foil (ii). FIG.7B shows velocity vectors (normalized / arbitrary unit) to demonstrate that splitting the helium flow at the inlet into two narrower channels directed onto the target insert surface (i) and cyclotron vacuum foil (ii) allows for optimal jet- flow at those regions. The flow is directed onto the beam strike area of the respective regions, where cooling is most advantageous.

[0054] FIGS. 8A and 8B illustrate an example front water-cooling assembly 58. This compartment also includes the snout 60, which attaches to the cyclotron beamline. FIG. 8B shows an example flow of water cooling on the cyclotron vacuum foil around the perimeter of the beam strike area. As shown in FIG. 8C, the cyclotron vacuum foil (e.g., HAVAR foil) is sandwiched between the front water-cooling assembly 58 on front (around the perimeter of the beam) and helium cooling assembly 56 at the back (at beam strike area). The cyclotron vacuum cooling components apply to both configurations of the target system 50. FIG. 8D shows a comparison of cyclotron vacuum foil performance with an older cooling system and the improved cyclotron vacuum foil cooling set-up described in the present disclosure with 10 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 directed helium jet flow at the beam strike area and added water cooling around the perimeter of the beam. The cyclotron vacuum foil is an important component in cyclotron target assemblies which separates cyclotron vacuum environment from the rest of the target system. This foil is ideally kept as thin as achievable to minimize beam energy degradation. Poor cooling can result in foil rupture and isotope production failure. Improved cooling on this region allows for thinner foils to be used (e.g., 20 µm instead of 50 µm). Improved cooling also increases the lifespan of the foil, reducing the need for frequent replacement between irradiation which contributed to cyclotron operator dose.

[0055] FIG.9 shows an example target system 50 assembled in the first configuration at the end of a cyclotron beamline featuring (i) a rear water-cooling assembly 52, (ii) a target holder 54 containing a target insert 10, (iii) a helium-cooling assembly 56, and (iv) a front water-cooling assembly 58, all assembled on the target mount 62 (v).

[0056] As will be described in more detail below, the first material and the first energy level are selected to produce the desired product for the first radionuclide. Similarly, the second material and the second energy level are selected to produce the desired product for the second radionuclide. The first material is also selected and the first radionuclide target 14 is designed (e.g., its thickness or other physical dimensions or characteristics are chosen) to degrade the particle beam to the desired second energy level. The first and second radionuclides may also be selected for a particular application. For instance, the first and second radionuclides may be selected as an imaging and therapeutic pair (theranostic) of radionuclides. In these instances, the first radionuclide may be selected as a therapeutic radionuclide and the second radionuclide may be selected as an imaging radionuclide, or vice versa.

[0057] As described above, the first radionuclide target 14 is composed of a first material. The first material may be a metallic material, such as a metal, a metal alloy, another suitable solid target, a liquid target, or the like. In some examples, the first material may be a naturally isotopic purity metal, may be isotropically enriched, or the like. The first material preferably maintains integrity at high beam energies (e.g., by having sufficient thermal conductivity and / or heat dissipation). To address materials that may have poorer thermal conductivity, longer, low current irradiation may be used. Additionally, or alternatively, a thermally conductive backing such as Kapton foil, high conductivity metal plating, or cladding may be applied to the first radionuclide production target 14. Additionally, or alternatively, thermal modeling can be used to improve the cooling design of the first radionuclide production target 14. 11 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614

[0058] The first radionuclide target 14 may be a plate, a foil, or the like. In some instances, the first radionuclide target 14 may be isotropically enriched. The first radionuclide target 14 may have any suitable shape and size. In some embodiments, the first radionuclide target 14 may be a generally rectangular shape. For instance, the first radionuclide target 14 may be a rectangle, a rectangle with rounded corners, and so on. In other embodiments, the first radionuclide target 14 may be circular, elliptical, or any other suitable shape. The physical dimensions of the first radionuclide target 14 may be selected based on the desired first radionuclide to be produced, the first energy level, and the second energy level to which the particle beam will be degraded by the first radionuclide target 14.

[0059] The first radionuclide target 14 may have a thickness in a range of 0.1–1.0 mm. As one non-limiting example, the first radionuclide target 14 may be composed of Zn-70 having a thickness in the range of 0.1–0.25 mm. The first energy level may be selected such that the Zn-70 is activated to produce Cu-67 as the first radionuclide. The thickness of the Zn- 70 and the first energy level may be selected such that the degraded particle beam will have a second energy level suitable for producing a desired second radionuclide. For instance, the thickness of the Zn-70 and the first energy level may be selected such that the degraded particle beam will have a second energy level suitable for producing Cu-64 as the second radionuclide in a second radionuclide target 16 composed of a suitable material (e.g., Ni-64). As a non- limiting example, the particle beam may be a proton beam with a first energy level of 16.5 MeV, which is an energy level commonly produced by small-medium medical cyclotrons. In this example, when the first radionuclide target 14 is a Zn-70 foil with a 0.1 mm thickness at 30 degrees to the baseline, the first radionuclide target 14 will degrade the energy of the proton beam to a second energy level of approximately 14 MeV, such that the proton beam will have the second energy level when incident on the second radionuclide target 16. Similarly, when the first radionuclide target is a Zn-70 foil with a 0.15 mm thickness at 30 degrees to the beamline, the first radionuclide target 14 will degrade the energy of the proton beam to a second energy level of approximately 12.4 MeV; when the first radionuclide target is a Zn-70 foil with a 0.20 mm thickness at 30 degrees to the beamline, the first radionuclide target 14 will degrade the energy of the proton beam to a second energy level of approximately 10 MeV; and when the first radionuclide target is a Zn-70 foil with a 0.25 mm thickness at 30 degrees to the beamline, the first radionuclide target 14 will degrade the energy of the proton beam to a second energy level of approximately 8 MeV. 12 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614

[0060] As another non-limiting example, the first radionuclide target 14 may be composed of Ti-50 having a thickness in the range of 0.2–0.3 mm. The first energy level may be selected such that the Ti-50 is activated to produce Sc-47 as the first radionuclide. The thickness of the Ti-50 and the first energy level may be selected such that the degraded particle beam will have a second energy level suitable for producing a desired second radionuclide. For instance, the thickness of the Ti-50 and the first energy level may be selected such that the degraded particle beam will have a second energy level suitable for producing Sc-44 as the second radionuclide in a second radionuclide target 16 composed of a suitable material (e.g., Ca-44). As a non-limiting example, the particle beam may be a proton beam with a first energy level of 16.5 MeV, which is an energy level commonly produced by small-medium medical cyclotrons. In this example, when the first radionuclide target 14 is a Ti-50 foil with a 0.2 mm thickness at 30 degrees to the beamline, the first radionuclide target 14 will degrade the energy of the proton beam to a second energy level of approximately 12 MeV, such that the proton beam will have the second energy level when incident on the second radionuclide target 16. Similarly, when the first radionuclide target is a Ti-50 foil with a 0.25 mm thickness at 30 degrees to the beamline, the first radionuclide target 14 will degrade the energy of the proton beam to a second energy level of approximately 11 MeV; and when the first radionuclide target is a Ti-50 foil with a 0.30 mm thickness at 30 degrees to the beamline, the first radionuclide target 14 will degrade the energy of the proton beam to a second energy level of approximately 10 MeV.

[0061] As described above, the second radionuclide target 16 is composed of a second material. The second material may be a metallic material, such as a metal, a metal alloy, or the like. In some examples, the second material may be a naturally isotopic purity metal.

[0062] The second radionuclide target 16 may be a plate, a foil, another suitable sold target, a liquid target, or the like. For example, the second radionuclide target 16 may include a substrate or insulator onto which the second target material is deposited (e.g., via plating, or the like). The second target material may include, for example, a pressed powder. Alternatively, the second radionuclide target 16 may include a solid plate of metal or metal alloy. The second radionuclide target 16 may have any suitable shape and size. In some embodiments, the second radionuclide target 16 may be a generally rectangular shape. For instance, the second radionuclide target 16 may be a rectangle, a rectangle with rounded corners, and so on. In other embodiments, the second radionuclide target 16 may be circular, elliptical, or any other suitable shape. 13 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614

[0063] The surface area of the second radionuclide target 16 may be smaller than the surface area of the first radionuclide target 14. Alternatively, the surface area of the second radionuclide target 16 may be the same as the surface area of the first radionuclide target 14, or may be larger than the surface area of the first radionuclide target 14. As a non-limiting example, the surface area of the second radionuclide target 16 can be between about 1 mm2and about 50 mm2. In some embodiments, the surface area of the second radionuclide target 16 can be about 25 mm2or less.

[0064] A non-limiting list of example radionuclide pairs, the corresponding target materials for the first and second radionuclide targets 14, 16, and the corresponding first and second energy levels is provided in Table 1 below. Table 1. Example Dual-Radionuclide Pairs and Corresponding Target Materials Radionuclide 1 Proton Target Radionuclide Proton Target Energy Material 1 2 Energy Material 2 Range (reaction) Range (reaction) (MeV) (MeV) 67Ga (Auger 18-1468Zn(p,2n)68Ga (PET) 12-668Zn(p,2n)therapy) 55 58 58m Co (PET)25-10 5Ni(14-8 8p, a) Co (AugerFe(p,n)Therapy) 7720-1 7776 76 Br (Auger0Se (p,n) Br (PET)16-10Se(p,n) Therapy) 89 Zr (PET)14-789 103 Y(p,n) Pd (Au12-5 103gerRh(p,n)Therapy) 89 8197mHg (Auger 12-197Zr (PET)r14-7- 89Y(p,n)n) 6 Au(p,n) (PET) therapy) 515252 Mn (PET)28-8Cr(p,2n)Mn (PET) 15-852Cr(p,n)14 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 149Tb (Alpha 65-45152Gd(p, 4n)203Pb (SPECT) 30-20205Tl (p,3n) Therapy)

[0065] FIG. 10 illustrates varying optimal production energy windows of different radionuclides to allow combinations to be selected for dual-radionuclide production. Combinations can be selected including one target being a therapeutic isotope and one target being an imaging isotope, both targets being imaging isotopes, or both targets being therapeutic isotopes. The examples are non limiting. The examples feature proton beam bombardment, but the concept can also be applied to isotope production from any heavy ion beam, such as deuteron and alpha beams.

[0066] FIGS.11–15 illustrate cross-sections for example pairs of radionuclides that can be produced using the dual-radionuclide target described in the present disclosure, where the shaded areas represent example production energy windows. FIG. 11 illustrates cross-section data for simultaneous production of the67Cu / 64Cu (Target 1 / Target 2) theranostic pair. FIG. 12 illustrates cross-section data for simultaneous production of the47Sc / 44Sc (Target 1 / Target 2) theranostic pair. FIG. 13 illustrates cross-section data for simultaneous production of the67Ga / 68Ga (Target 1 / Target 2) theranostic pair. FIG. 14 illustrates cross-section data for simultaneous production of the55Co / 58mCo (Target 1 / Target 2) theranostic pair. FIG. 15 illustrates cross-section data for simultaneous production of the123I / 124I (Target 1 / Target 2) theranostic pair.

[0067] After radionuclides are produced using the disclosed dual-radionuclide production target, the target is processed to extract, separate, and package the produced radionuclides. It is an aspect of the present disclosure to provide a system for processing and distributing the dual-radionuclide target described above.

[0068] Referring now to FIGS. 16A–16B, 17A–17D, and 18A–18C, an example radionuclide processing and distribution system 700 is illustrated. The radionuclide processing and distribution system 700 generally includes a radionuclide target collection system 710 and a radionuclide target processing system 730.

[0069] As shown in FIGS. 17A–17D, the radionuclide target collection system 710 receives the dual-radionuclide production target 10 after it has been irradiated and provides the dual-radionuclide production target 10 to the radionuclide target processing system 730 where the first and second radionuclides are extracted. The radionuclide target collection system 710 includes a receptacle 712 that receives the dual-radionuclide production target 10 from the 15 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 radionuclide production system. The receptacle 712 may include a chute, or the like. When the dual-radionuclide production target 10 enters the receptacle 712 it is flipped within the receptacle 712 to ensure a consistent orientation of the dual-radionuclide production target 10 when exiting the receptacle 712. At the bottom of receptacle 712, the dual-radionuclide production target 10 is received by a rotatable tray 714. The rotatable tray 714 may be rotated to adjust the orientation of the dual-radionuclide production target 10, as needed, before entering the radionuclide target processing system 730. This additional rotation of the dual- radionuclide production target 10 helps ensure a consistent orientation of the dual-radionuclide production target 10 when entering the radionuclide target processing system 730.

[0070] As shown in FIGS. 18A–18C, the radionuclide target processing system 730 receives the dual-radionuclide production target 10 from the radionuclide target collection system 710 and processes the dual-radionuclide production target 10 to extract the first and second radionuclide targets 14, 16 for processing and extraction of the first and second radionuclides. In some instances, an armature 720 (e.g., a suction tool arranged at the end of a robotic arm or other movable armature, as shown in FIG. 16B) can transport the dual- radionuclide production target 10 from the radionuclide target collection system 710 to the radionuclide target processing system 730.

[0071] The radionuclide target processing system 730 includes a receptacle 732 that receives the dual-radionuclide production target 10. The receptacle 732 may include, for example, a tray or slot that is dimensioned to receive and retain the dual-radionuclide production target 10. A hook or other coupling attaches to the first radionuclide target 14. The first radionuclide target 14 may then be removed from the dual-radionuclide production target 10 by pulling the first radionuclide target 14 away from the dual-radionuclide production target 10, such as by actuating the hook or other coupling via a motorized switch, or the like. The second radionuclide target 16 can then be removed from the dual-radionuclide production target 10 by an actuator. The actuator may be controlled, for example, by a button or the like.

[0072] After the first and second radionuclide targets 14, 16 have been separated from the dual-radionuclide production target 10, they may be collected for processing (e.g., chemical processing) to extract the first and second radionuclides. The separated radionuclides may then be packaged for distribution (e.g., within a clinical site, for shipment to other clinical sites, etc.).

[0073] Referring now to FIG. 19, an example radionuclide production system 1900 is illustrated. The radionuclide production system 1900 generates radioactive isotopes (i.e., 16 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 radionuclides or radionuclides), which are used in a variety of applications including medical imaging, cancer treatment, and industrial applications. In general, the radionuclide production system 1900 includes a particle accelerator 1910, a target assembly 1920, and a radionuclide processing unit 1930.

[0074] The particle accelerator 1910 accelerates charged particles to high energies. These high-energy charged particles are then directed onto a target (i.e., the dual-radionuclide production target 10) to produce radionuclides through nuclear reactions induced in the target materials. In general, the particle accelerator 1910 may include an accelerator 1912 (e.g., a cyclotron, a synchrotron, a linac) that generates a particle beam 1914 of charged particles, a beamline 1916 that guides the particle beam 1914 from the accelerator 1912 to the target assembly 1920, and a controller 1918 for controlling operation of the particle accelerator 1910. For instance, the controller 1918 can monitor and adjust the particle beam energy, the particle beam direction, and the like, by controlling components of the accelerator 1912 and / or beamline 1914.

[0075] As one example, the particle beam 1914 generated by the particle accelerator 1910 is a proton beam. In other examples, the particle accelerator 1910 may generate other heavy ion beams, such as a deuteron beam, a helium-3 beam, an alpha beam, a lithium-7 beam, a carbon-12 beam, or the like. In still other examples, the particle beam accelerator 1910 may instead be a neutron source that generates the particle beam 1914 as a neutron beam. The particle beam 1914 may also be generated by other systems and processes, such as photonuclear reactions.

[0076] As described above, the target assembly 1920 can include the dual-radionuclide production target 10. The target assembly 1920 may therefore include a target holder, such as the target backing 18 and cover foil 20 of the target body 12. The target holder mechanically supports the target material (e.g., the first and second radionuclide targets 14, 16) and aligns them within the beamline of the particle accelerator 1910. In some embodiments, the target assembly 1920 may also include a cooling system to remove heat generated during the irradiation process to prevent damage to the first and / or second radionuclide targets 14, 16 and to maintain efficiency.

[0077] The radionuclide processing unit 1930 extracts the produced radionuclides from the target materials of the first and second radionuclide targets 14, 16 and processes them to obtain the final radionuclide products suitable for clinical use. The radionuclide processing unit 17 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 1930 may also include chemical processing equipment (e.g., reactors, separators, purifiers) to isolate the first and second radionuclides from other byproducts.

[0078] Additionally, the radionuclide processing unit 1930 packages the radionuclide products for transportation or subsequent use. For example, the radionuclide processing unit 1930 can include components for packaging the first and second radionuclide products into specialized containers that shield radiation and prevent leaks.

[0079] Referring now to FIG.20, a flowchart is illustrated as setting forth the steps of an example method for producing a plurality of radionuclides in a single production run using a dual-radionuclide production target according to embodiments described in the present disclosure. The method includes arranging a radionuclide target holder in a beam path of a particle beam source, as indicated at step 2002. The radionuclide target holder holds a first radionuclide target and a second radionuclide target aligned within the beam path. For example, the radionuclide target holder may be a dual-radionuclide production target such as those illustrated in FIGS.1A–1F. As described above, the first radionuclide target is composed of a first material that when irradiated by a particle beam at a first energy level produces a first radionuclide and the second radionuclide target is composed of a second material that when irradiated with the particle beam at a second energy level that is lower than the first energy level produced a second radionuclide.

[0080] The radionuclide target holder is then irradiated with a particle beam from the particle beam source, such that the particle beam irradiates the first radionuclide target at a first energy level before irradiating the second radionuclide target at a second energy level that is lower than the first energy level, as indicated at step 2004. The particle beam source may be a particle accelerator, such as a linear accelerator (i.e., a linac), a cyclotron, a synchrotron, or the like. The particle beam may be a charged particle beam, such as a proton beam, a deuteron beam, an He-4 beam, an Li-7 beam, a C-12 beam, or another ion beam, including another heavy ion beam. Alternatively, the particle beam source may be a neutron source, such that the particle beam is a neutron beam. In still other examples, the particle beam source may be a photonuclear reaction source, such that the particle beam is an electron beam, a photon beam, or the like.

[0081] When the first radionuclide target is irradiated with the particle beam at the first energy level, the first radionuclide is produced in the first material. As the particle beam passes through the first radionuclide target, the energy of the particle beam is degraded from the first energy level to the second energy level. The second radionuclide target is then irradiated with 18 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 the particle beam at the second energy level, thereby producing the second radionuclide in the second material.

[0082] The first radionuclide is then extracted from the first material, thereby forming a first separated radionuclide product, as indicated at step 2006. Likewise, the second radionuclide is extracted from the second material, thereby forming a second separated radionuclide product, as indicated at step 2008. By way of example, the irradiated radionuclide target can be processed using the radionuclide processing and distribution system 700 illustrated in FIGS.16A–16B, 17A–17D, and 18A–18C.

[0083] In an example study, the systems and methods described in the present disclosure were validated for producing different radionuclide pairs. In one aspect of the study, the design of the dual-radionuclide target (target holder and insert) was optimized to enhance heat dissipation and production efficiency. In one configuration, the dual-radionuclide target was constructed using natural targets, such as yttrium, gold, rhodium etc. In another aspect of the study, the isotope production and processing system was validated by manufacturing clinically important Cu-64 and Cu-67 as a theranostic pair, and their application in radiolabeling of clinically relevant fibroblast activation protein inhibitor (FAPI), and other emerging molecules. In yet another aspect of the study, the versatility of the disclosed systems and methods was validated by manufacturing Ga-67 and Ga-68 as a therapeutic pair, and their application in bacterial infection imaging and radionuclide therapy.

[0084] As described above, the dual-radionuclide target used in the example study replaces the degrader foil at the beam strike area with a foil target suitable for medical radionuclide production. With this design, the foil target serves two purposes: it reduces the beam energy to a suitable energy for isotope production on a second target, and in-doing so becomes activated with a medically relevant radionuclide, which can be easily extracted. Following this approach, in a single production run two radionuclides are produced. This approach enables theranostic pairs to be produced in a single run without cross-contamination and enhances the utility of medical cyclotrons and other accelerators. Advantageously, instead of each radionuclide requiring its own production run, resources, and time on the cyclotron (or accelerator) schedule, two (or more) radionuclides can be generated simultaneously.

[0085] In the example study, the feasibility and scalability of the production of theranostic pairs and other combinations of radionuclides in a single irradiation were evaluated. The application of these radionuclides in radiolabeling of clinically emerging FAPI molecules, and other targeting vectors, for theranostic applications and bacterial infection imaging was 19 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 also investigated. The goal of the example study was to achieve simultaneous co-production of two different radionuclides without cross-contamination and to demonstrate their usefulness. Example applications for theranostic pair production are shown in FIGS.2A, 2B, 3A, 3B, 4, 5, and 6.

[0086] As described above, the energy lost in a standard degrader foil is captured and repurposed for secondary radionuclide production at no detriment to the original target. The thickness of the first target is tailored to capture the required energy width for radionuclide production and to sufficiently degrade the beam energy for the second target. Currently, the only way to simultaneously produce two radionuclides on separate targets would be to maintain a second beamline, which significantly lowers yields, or to purchase a second cyclotron, which requires immensely higher costs, space, and personnel commitment and maintenance.

[0087] In this example study, a dual-radionuclide target was constructed, and four test runs were performed using two different target pairs:44Sc / 47Sc (n = 2 runs) and89Zr / 44Sc (n = 2 runs). The dual-radionuclide target design shown in FIGS. 1A–1D was used. In this design, both the first and second targets are physically apart from each other and not in contact with each other, thereby mitigating potential cross-contamination and enhancing heat dissipation. A remotely controlled target distribution and processing system (e.g., the processing and distribution system illustrated in FIG. 7) was used to automate remote separation of the two targets post irradiation to minimize radiation exposure to the worker and to further allow independent processing for selective purification and radiolabeling.

[0088] In this example study, the dual-radionuclide production target described in the present disclosure was used to produce two different radionuclide pairs: the first pair being Zr- 89 and Sc-44, and the second pair being Sc-47 and Sc-44. For each radionuclide pair, two experiments were run using different target configurations, beam currents, and / or irradiation times. A summary of the validation experiments is provided in Table 2. Table 2. Dual-Radionuclide Production Validation Experiments Radionuclide Target 1 Target Beam Irradiation EOB Activity EOB Activity Pair 2 Current Time Target 1 Target 2 89 44 nat 80 mg Zr / Sc 0.1 mm Y nat 40 µA 1 hr Not measured Not Measured CaO 89 44 nat 80 mg 34.89 mCi 6.05 mCi Zr / Sc 0.25 mm Y nat 40 µA 30 min 89 44 CaO ( Zr) ( Sc) 20 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 47 44 nat 80 mg Not measured 2.82 mCi Sc / Sc 0.25 mm Ti nat 20 µA 30 min (performance 44 CaO test) ( Sc) nat Not measured 47 44 80 mg (per Not measured 0.25 mm formance Sc / Sc Ti nat 20 µA 30 min (performance + Kapton tape CaO test) test)

[0089] FIGS. 21A, 21B, 22A, and 22B demonstrate results from an example dual- radionuclide production validation experiment using the target systems described in the present disclosure. FIG. 21A shows a comparison of integrity of 0.1 mmnatY foil during 1 hr 40 µA production of89Zr / 44Sc (Target 1 / Target 2) PET radionuclide pair. Enhanced cooling set-up avoided foil rupture during irradiation for scalable production. FIG.21B shows a comparison of integrity of 80 mg pressednatCaO powder during 1 hr 40 µA production of89Zr / 44Sc (Target 1 / Target 2) PET radionuclide pair. Enhanced cooling set-up avoided target fragmentation for scalable production. FIG. 22A shows an HPGe spectrum of dissolved Target 1 (89Zr) after production of the89Zr / 44Sc (Target 1 / Target 2) PET radionuclide pair. When targets remain intact and physically apart, no cross-contamination is detected. FIG. 22B shows an HPGe spectrum of dissolved Target 2 (44Sc) after production of the89Zr / 44Sc (Target 1 / Target 2) PET radionuclide pair. When targets remain intact and physically apart, no cross-contamination is detected. Experimental results are provided in Table 3 below. Table 3. Dual-Radionuclide Production Validation Experiments on Novel Target System Radionuclid Beam Target 1 Target 1 Target 2 Target 2 e Pair Parameter EOB EOB s Activity Activity (mCi) (mCi) 89Zr / 44Sc 1 hr 40 µA 0.1 mmnatY; 10.5 (89Zr) 80 mgnatCaO; 9.8 (44Sc) [89Y(p,n)89Zr] [44Ca(p,n)44Sc] 89Zr / 44Sc 1 hr 40 µA 0.2 mmnatY; 13.61 (89Zr) 80 mgnatCaO; 7.11 (44Sc) [89Y(p,n)89Zr] [44Ca(p,n)44Sc] 89Zr / 44Sc 2 hr 40 µA 0.2 mmnatY; 31.2 (89Zr) 80 mgnatCaO; 15.2 (44Sc) [89Y(p,n)89Zr] [44Ca(p,n)44Sc] 47Sc / 44Sc 1 hr 40 µA 0.5 mmnatTi Not 80 mgnatCaO; Not [50Ti(p,α)47Sc] measured [44Ca(p,n)44Sc] measured (performanc (performanc e test) e test) 21 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 67Ga / 68Ga 1 hr 20 µA 0.15 mmnatZn 0.7 (67Cu) 0.25 mmnatZn; 88.3 (68Ga) [68Zn(p,2n)67Ga [68Zn(p,n)68Ga ] ] 67Cu / 64Cu 1 hr 20 µA 0.25 mmnatZn - 0.25 mmnatNi; 1.34 [70Zn(p,a)67Cu] [64Ni(p,n)64Cu]

[0090] The present disclosure has described one or more preferred embodiments, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of the invention. 22 QB\630666.01614\98040527.3

Claims

Mayo 2024-254 Q&B Docket: 630666.01614 CLAIMS 1. A dual-radionuclide production target, comprising: a first radionuclide target composed of a first material that when irradiated with a particle beam having an energy at a first energy level causes a first radionuclide to form in the first material while degrading the energy of the particle beam to a second energy level; a second radionuclide target composed of a second material that when irradiated with the particle beam having its energy at the second energy level causes a second radionuclide to form in the second material; and a target body that holds the first radionuclide target and the second radionuclide target in alignment along an irradiation beam axis such that particle beam irradiates the first radionuclide target before irradiating the second radionuclide target.

2. The dual-radionuclide production target of claim 1, wherein the first radionuclide target comprises one of a foil or a plate.

3. The dual-radionuclide production target of claim 1 or 2, wherein the second radionuclide target comprises one of a foil, a plate, pressed powder, or a liquid target.

4. The dual-radionuclide production target of any one of claims 1–3, wherein the first material comprises Zn-70 and the second material comprises Ni-64.

5. The dual-radionuclide production target of claim 4, wherein the first radionuclide is Cu-67 and the second radionuclide is Cu-64.

6. The dual-radionuclide production target of claim 5, wherein the particle beam comprises a proton beam and the first energy level is in a range of about 12 MeV to about 18 MeV and the second energy level is in a range of about 6 MeV to about 12 MeV.

7. The dual-radionuclide production target of any one of claims 1–3, wherein the first material comprises Ti-50 and the second material comprises Ca-44. 23 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 8. The dual-radionuclide production target of claim 7, wherein the first radionuclide is Sc-47 and the second radionuclide is Sc-44.

9. The dual-radionuclide production target of claim 8, wherein the particle beam comprises a proton beam and the first energy level is in a range of about 10 MeV to about 24 MeV and the second energy level is in a range of about 5 MeV to about 11 MeV.

10. The dual-radionuclide production target of any one of claims 1–3, wherein the first material comprises Zn-68 and the second material comprises Zn-68.

11. The dual-radionuclide production target of claim 10, wherein the first radionuclide is Ga-67 and the second radionuclide is Ga-68.

12. The dual-radionuclide production target of claim 11, wherein the particle beam comprises a proton beam and the first energy level is in a range of about 14 MeV to about 18 MeV and the second energy level is in a range of about 6 MeV to about 12 MeV.

13. The dual-radionuclide production target of any one of claims 1–3, wherein the first material comprises Te-124 and the second material comprises Te-124.

14. The dual-radionuclide production target of claim 13, wherein the first radionuclide is I-123 and the second radionuclide is I-124.

15. The dual-radionuclide production target of claim 14, wherein the particle beam comprises a proton beam and the first energy level is in a range of about 16 MeV to about 30 MeV and the second energy level is in a range of about 7 MeV to about 12 MeV.

16. The dual-radionuclide production target of any one of claims 1–3, wherein the first material comprises Ra-226 and the second material comprises Zn-68.

17. The dual-radionuclide production target of claim 16, wherein the first radionuclide is Ac-225 and the second radionuclide is Ga-68. 24 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 18. The dual-radionuclide production target of claim 17, wherein the particle beam comprises a proton beam and the first energy level is in a range of about 14 MeV to about 20 MeV and the second energy level is in a range of about 6 MeV to about 12 MeV.

19. The dual-radionuclide production target of claim 16, wherein the first radionuclide is Co-55 and the second radionuclide is Co-58m.

20. The dual-radionuclide production target of claim 17, wherein the particle beam comprises a proton beam and the first energy level is in a range of about 10 MeV to about 25 MeV and the second energy level is in a range of about 14 MeV to about 6 MeV.

21. The dual-radionuclide production target of any one of claims 1–3, wherein the first material comprises Fe-58 and the second material comprises Ni-58.

22. The dual-radionuclide production target of any one of claims 1–3, wherein the first radionuclide is Br-77 and the second radionuclide is Br-76.

23. The dual-radionuclide production target of any one of claims 1–3, wherein the first radionuclide is Zr-89 and the second radionuclide is Pd-103.

24. The dual-radionuclide production target of any one of claims 1–3, wherein the first radionuclide is Zr-89 and the second radionuclide is Hg-197m.

25. The dual-radionuclide production target of any one of claims 1–3, wherein the first radionuclide is Mn-51 and the second radionuclide is Mn-52.

26. The dual-radionuclide production target of any one of claims 1–3, wherein the first radionuclide is Pb-203 and the second radionuclide is Re-186.

27. The dual-radionuclide production target of any one of claims 1–3, wherein the first radionuclide is I-123 and the second radionuclide is I-124. 25 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 28. The dual-radionuclide production target of any one of claims 1–3, wherein the first radionuclide is Sb-117 and the second radionuclide is Sb-119.

29. The dual-radionuclide production target of any one of claims 1–3, wherein the first radionuclide is In-111 and the second radionuclide is Ti-45.

30. The dual-radionuclide production target of any one of claims 1–3, wherein the first radionuclide is Tb-149 and the second radionuclide is Pb-203.

31. The dual-radionuclide production target of claim 1, wherein the target body comprises a target backing having formed therein a first recess sized to receive the first radionuclide target and a second recess sized to receive the second radionuclide target.

32. The dual-radionuclide production target of claim 31, wherein the target backing comprises lateral lips configured to receive and retain a cover foil.

33. The dual-radionuclide production target of claim 32, wherein the cover foil is slidably insertable into the lateral lips.

34. The dual-radionuclide production target of claim 1, wherein the first recess and the second recess are sized such that the first radionuclide target is physically separated from the second radionuclide target when the first radionuclide target is retained in the first recess and the second radionuclide target is retained in the second recess.

35. The dual-radionuclide production target of claim 31, wherein the second recess is nested within the first recess.

36. The dual-radionuclide production target of claim 31, wherein the target body further comprises a target foil configured to couple to a front surface of the target backing, wherein the target foil includes an aperture formed therein, wherein the aperture is sized to permit particle beam to irradiate the first radionuclide target and the second radionuclide target. 26 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 37. The dual-radionuclide production target of claim 1, wherein the first radionuclide target has a thickness in a range of about 0.1 mm to about 1.0 mm.

38. The dual-radionuclide production target of claim 1, wherein the first radionuclide target is configured to generate the first radionuclide as an imaging radionuclide and the second radionuclide target is configured to generate the second radionuclide as a therapeutic radionuclide.

39. The dual-radionuclide production target of claim 1, wherein the first radionuclide target is configured to generate the first radionuclide as a therapeutic radionuclide and the second radionuclide target is configured to generate the second radionuclide as an imaging.

40. The dual-radionuclide production target of claim 1, wherein the first radionuclide target is configured to generate the first radionuclide as a first imaging radionuclide and the second radionuclide target is configured to generate the second radionuclide as a second imaging radionuclide.

41. The dual-radionuclide production target of claim 1, wherein the first radionuclide target is configured to generate the first radionuclide as a first therapeutic radionuclide and the second radionuclide target is configured to generate the second radionuclide as a second therapeutic radionuclide.

42. The dual-radionuclide production target of claim 1, further comprising a target system that houses the target body, wherein the target system comprises: a rear water-cooling assembly; a target holder configured to retain the target body; a helium-cooling assembly; and a front water-cooling assembly.

43. The dual-radionuclide production target of claim 42, wherein the target system further comprises a target mount configured to assemble and retain the rear water-cooling assembly, target holder, helium-cooling assembly, and front water-cooling assembly together. 27 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 44. The dual-radionuclide production target of claim 42, wherein the target holder comprises a front part and a back part that enclose the target body.

45. The dual-radionuclide production target of claim 44, wherein the target holder further comprises an electronically controlled release mechanism configured to release the target body from between the front part and the back part.

46. The dual-radionuclide production target of claim 42, wherein the rear water- cooling assembly comprises flow channels configured to direct liquid coolant along dimensions of the target body.

47. The dual-radionuclide production target of claim 42, wherein the helium- cooling assembly comprises flow channels configured to direct helium flow onto a surface of the target body and onto a cyclotron vacuum foil.

48. The dual-radionuclide production target of claim 42, wherein the front water- cooling assembly comprises a cyclotron vacuum foil and water cooling channels configured to provide cooling around a perimeter of a beam strike area on the cyclotron vacuum foil.

49. The dual-radionuclide production target of claim 42, wherein the front water- cooling assembly further comprises a beamline connection snout.

50. The dual-radionuclide production target of claim 1, wherein the target body is oriented at an angle of 90 degrees to an irradiation beam axis when arranged in the target holder.

51. The dual-radionuclide production target of claim 1, wherein the target body is oriented at an angle of 30 degrees to an irradiation beam axis when arranged in the target holder.

52. The dual-radionuclide production target of claim 1, wherein the target body is configured to retain the first radionuclide target and the second radionuclide target while 28 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 maintaining physical separation therebetween during irradiation to prevent cross- contamination.

53. The dual-radionuclide production target of claim 1, wherein the second radionuclide target has a surface area that is smaller than a surface area of the first radionuclide target.

54. The dual-radionuclide production target of claim 53, wherein the surface area of the second radionuclide target is between about 1 mm² and about 50 mm².

55. A target system for dual-radionuclide production, comprising: the dual-radionuclide production target of claim 1; a cooling system configured to provide thermal management during irradiation; and a release mechanism configured to remotely release the target body after irradiation.

56. A method for producing a plurality of radionuclides in a single production run, the method comprising: arranging a radionuclide target holder in a beam path of a particle beam source, wherein the radionuclide target holder holds a first radionuclide target and a second radionuclide target aligned within the beam path, wherein the first radionuclide target is composed of a first material and the second radionuclide target is composed of a second material; irradiating the radionuclide target holder with a particle beam from the particle beam source such that the particle beam irradiates the first radionuclide target at a first energy level before irradiating the second radionuclide target at a second energy level that is lower than the first energy level; wherein irradiating the first radionuclide target with the particle beam at the first energy level produces a first radionuclide in the first material and degrades an energy of the particle beam from the first energy level to the second energy level; and wherein irradiating the second radionuclide target with the particle beam at the second energy level produces a second radionuclide in the second material. 29 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 57. The method of claim 56, further comprising extracting the first radionuclide from the first material, thereby forming a first separated radionuclide product and extracting the second radionuclide from the second material, thereby forming a second separated radionuclide product.

58. The method of claim 56, wherein the particle beam source comprises a particle accelerator.

59. The method of claim 58, wherein the particle accelerator comprises one of a linear accelerator, a cyclotron, or a synchrotron.

60. The method of claim 59, wherein the particle beam comprises a charged particle beam.

61. The method of claim 60, wherein the charged particle beam comprises one of a proton beam, a deuteron beam, a He-3 beam, a Li-7 beam, or a C-12 beam.

62. The method of claim 56, wherein the particle beam source comprises a neutron source and the particle beam comprises a neutron beam.

63. The method of claim 56, wherein the particle beam source comprises a photonuclear reaction source and the particle beam comprises one of an electron beam or a photon beam.

64. A radionuclide processing system to separate two radionuclide products from a dual-radionuclide production target, comprising: a radionuclide target collection system comprising: a receptacle to receive a dual-radionuclide production target that has been irradiated by a particle beam, wherein the dual-radionuclide production target includes a first radionuclide target having formed therein a first radionuclide and a second radionuclide target having formed therein a second radionuclide; 30 QB\630666.01614\98040527.3Mayo 2024-254 Q&B Docket: 630666.01614 a rotatable tray to receive the dual-radionuclide production target from the receptacle and to rotate the dual-radionuclide production target to a consistent orientation; a radionuclide processing system comprising: a receptacle to receive the dual-radionuclide production target from the radionuclide target collection system; a first extraction assembly to extract the first radionuclide target from the dual- radionuclide production target; and a second extraction assembly to extract the second radionuclide target from the dual-radionuclide production target.

65. The radionuclide processing system of claim 64, further comprising an armature configured to transport the dual-radionuclide production target from the radionuclide target collection system to the radionuclide processing system.

66. The radionuclide processing system of claim 65, wherein the armature comprises a suction tool arranged at an end of a robotic arm.

67. The radionuclide processing system of claim 64, wherein the first extraction assembly comprises a coupling mechanism configured to attach to the first radionuclide target and remove the first radionuclide target from the dual-radionuclide production target.

68. The radionuclide processing system of claim 67, wherein the coupling mechanism comprises a hook.

69. The radionuclide processing system of claim 64, wherein the second extraction assembly comprises an actuator configured to remove the second radionuclide target from the dual-radionuclide production target. 31 QB\630666.01614\98040527.3

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