Patent Number: 060118253
Section: claims

1. A method for producing a radionuclide from a target nuclide using an accelerator capable of generating a beam of charged particles at energies of at least about 5 MeV, the method comprising loading a solid target comprising the target nuclide in a target holder mounted in line with the charged-particle beam generated by the accelerator and adapted to releasably hold the target in position for irradiation by the charged-particle beam,  irradiating the target held by the target holder with the charged-particle beam at energies of at least about 5 MeV to form the radionuclide,  removing the irradiated target from the target holder, transferring the removed irradiated target to an automated separation system, and  separating the radionuclide from unreacted target nuclide using the automated separation system.  transferring the irradiated target from the target holder to a fluid conveyance system,  conveying the irradiated target through the conveyance system, and  transferring the irradiated target from the conveyance system to the separation system.  loading a solid target comprising the target nuclide in a target holder,  irradiating the target with the charged-particle beam at energies of at least about 5 MeV to form the radionuclide,  transferring the irradiated target from the target holder to a fluid conveyance system comprising a transfer fluid moving through a transfer line,  conveying the irradiated target using the conveyance system, and  separating the radionuclide from unreacted target nuclide.  loading a solid target in a target holder adapted for use with the accelerator, the target comprising a substrate consisting essentially of an inert material and a target layer electroplated on a surface of the substrate, the target laver consisting essentially of a target nuclide capable of reacting with charged particles generated by the accelerator at energies ranging from about 5 MeV to about 25 MeV to form the radionuclide and having a projected thickness that will produce at least about 50% of the thick target yield for the reaction,  irradiating the target with a beam of charged particles generated by the accelerator for at least about one hour to form the radionuclide, the beam having an energy ranging from about 5 MeV to about 25 MeV and a current sufficient to produce a clinically significant yield of the radionuclide,  removing the irradiated target from the target holder,  transferring the removed irradiated target to an automated separation system, and  separating the radionuclide from unreacted target nuclide using the automated separation system.  loading a solid target in a target holder adapted for use with the accelerator, the target comprising a substrate consisting essentially of an inert material and a target layer electroplated on a surface of the substrate, the target layer consisting essentially of a target nuclide capable of reacting with charged particles generated by the accelerator at energies ranging from about 5 MeV to about 25 MeV to form the radionuclide and having a projected thickness that will produce at least about 50% of the thick target yield for the reaction,  irradiating the target with a beam of charged particles generated by the accelerator for at least about one hour to form the radionuclide, the beam having an energy ranging from about 5 MeV to about 25 MeV and a current sufficient to produce a clinically significant yield of the radionuclide,  transferring the irradiated target from the target holder to a fluid conveyance system  conveying the irradiated target using the conveyance system, and  transferring the irradiated target from the conveyance system to the separation system.  loading the target in a target holder suitable for use with an accelerator capable of generating the proton beam at energies greater than about 5 MeV,  irradiating a target comprising isotonically enriched .sup.64 Ni with a proton beam to produce .sup.64 Cu according to the reaction .sup.64 Ni(p,n).sup.64 Cu in an amount which is at least sufficient for preparing a radioimaging agent, the proton beam having an energy of at least about 5 MeV and a current at least sufficient to produce an amount of .sup.64 Cu sufficient for clinical use in a radioimaging agent during the period of irradiation,  removing the irradiated target from the target holder,  transferring the removed irradiated target to an automated separation system suitable for separating .sup.64 Cu from unreacted .sup.64 Ni, and  separating .sup.64 Cu from unreacted .sup.64 Ni, the separated .sup.64 Cu having a specific activity at least sufficient for clinical use in a radioimaging agent.  loading the .sup.64 Ni target in a target holder adapted for use with a proton accelerator capable of generating a proton beam at energies ranging from about 5 MeV to about 25 MeV, the target holder including an elongated body and a cooling head, the body having an irradiation chamber and a front seat adapted to sealingly engage the target, the front seat having an aperture for allowing fluid communication between the irradiation chamber and the target, the cooling head having a cavity and a back seat adapted to sealingly engage the target, the back seat having an aperture for allowing fluid communication between the cavity and the target, the cooling head being retractable from the body to allow for loading and unloading the target from the target holder and being engageable with the body to hold the target against the body during irradiation, the target being loaded in the target holder by positioning the target against the front seat of the body or the back seat of the cooling head and drawing a vacuum in the chamber or in the cavity, respectively, to hold the target in such position before the cooling head is engaged,  engaging the cooling head to hold the target against the body,  after the target is irradiated, retracting the cooling head from the body and holding the irradiated target in place against the cooling head or against the body by vacuum after the cooling head is retracted, and  unloading the irradiated target from the target holder by pressurizing the chamber or the cavity, the pressure being effective to act through the aperture in the front seat or back seat, respectively, to separate the target from the front seat or back seat and eject the target for further processing.  exposing the target to an acidic solution in the dissolution vessel to dissolve the target layer off of the substrate, thereby forming a target-layer solution comprising .sup.64 Cu, .sup.64 Ni and other radionuclides,  passing the target-layer solution through the anion-exchange column and collecting a first eluate therefrom, the first eluate being substantially enriched in nickel relative to copper, and  passing water or an acidic solution having a normality of about 0.5 N through the anion-exchange column and collecting a second eluate therefrom, the second eluate being substantially enriched in .sup.64 Cu relative to other radionuclides or impurities. 2. The method as set forth in claim 1 wherein the step of transferring the removed irradiated target to the separation system includes conveying the irradiated target through a fluid conveyance system comprising a transfer fluid moving through a transfer line. 3. The method as set forth in claim 2 wherein the transfer fluid contacts the irradiated target to transfer the irradiated target through the transfer line without using a transfer capsule. 4. The method as set forth in claim 1 wherein the step of transferring the removed irradiated target to the separation system includes 5. The method as set forth in claim 1 wherein the target holder comprises an elongated body adapted to sealingly engage the accelerator and a cooling head, the body having an irradiation chamber and a front seat adapted to sealingly receive the target, the front seat having an aperture for allowing fluid communication between the irradiation chamber and the target, the cooling head including a cavity and a back seat adapted to sealingly receive the target, the back seat having an aperture for allowing fluid communication between the cavity and the target, the head being retractable from the body to allow for loading and unloading the target from the target holder and being engageable with the body to hold the target against the front seat of the body during irradiation, and wherein the step of loading the target in the target holder comprises positioning the target against the front seat of the body or the back seat of the cooling head and drawing a vacuum in the irradiation chamber or in the cavity, respectively, to hold the target in such position at least until the head is engaged with the chamber. 6. The method as set forth in claim 1 wherein the target holder comprises an elongated body and a cooling head, the body including an irradiation chamber and a front seat adapted to sealingly receive the target, the front seat having an aperture for allowing fluid communication between the irradiation chamber and the target, the cooling head including a cavity and a back seat adapted to sealingly receive the target, the back seat having an aperture for allowing fluid communication between the cavity and the target, the cooling head being retractable from the body to allow for loading and unloading the target from the target holder and being engageable with the body to hold the target against the front seat of the body during irradiation, and wherein the step of removing the irradiated target from the target holder comprises retracting the cooling head from the body after the target is irradiated, the irradiated target being held in place against the cooling head seat or against the body seat by vacuum after the cooling head is retracted, and pressurizing the chamber or the cavity, the pressure being effective to act through the aperture in the front seat or back seat, respectively, to separate the target from the front seat or back seat and eject the target for further processing. 7. The method as set forth in claim 1 wherein the target is irradiated with a charged particle beam generated in a low or medium energy accelerator at a beam energy ranging from about 5 MeV to about 25 MeV. 8. The method as set forth in claim 1 wherein the target nuclide is .sup.64 Ni and the target is irradiated with protons to form .sup.64 Cu according to the reaction .sup.64 Ni(p,n).sup.64 Cu. 9. A method for producing a radionuclide from a target nuclide using an accelerator capable of generating a beam of charged particles at energies of at least about 5 MeV, the method comprising 10. The method as set forth in claim 9 wherein the irradiated target is removed from the target holder prior to being conveyed to the conveyance system. 11. The method as set forth in claim 9 wherein the transfer fluid contacts the irradiated target to transfer the irradiated target through the transfer line without using a transfer capsule. 12. A method for producing a radionuclide from a target nuclide using an accelerator capable of generating a beam of charged particles at energies ranging from about 5 MeV to about 25 MeV, the method comprising 13. A method for producing a radionuclide from a target nuclide using an accelerator capable of generating a beam of charged particles at energies ranging from about 5 MeV to about 25 MeV, the method comprising 14. A method for producing .sup.64 Cu suitable for use in preparing a radiopharmaceutical agent for clinical applications, the method comprising 15. The method as set forth in claim 12 wherein the target layer has a projected thickness that will produce at least about 75% of the thick target yield. 16. The method as set forth in claim 12 wherein the target layer has dimensions that define a target area and the charged-particle beam impinges the target over an area which substantially matches the target area. 17. The method as set forth in claim 12 wherein the charged-particles generated by the accelerator travel unimpeded from the accelerator to the target during irradiation without passing through an attenuating foil or window. 18. The method as set forth in claim 12 wherein the target nuclide is .sup.64 Ni and the target is irradiated with protons to form .sup.64 Cu according to the reaction .sup.64 Ni(p,n).sup.64 Cu. 19. The method as set forth in claim 13 wherein the target layer has a projected thickness that will produce at least about 75% of the thick target yield. 20. The method as set forth in claim 13 wherein the target layer has dimensions that define a target area and the charged-particle beam impinges the target over an area which substantially matches the target area. 21. The method as set forth in claim 13 wherein the charged-particles generated by the accelerator travel unimpeded from the accelerator to the target during irradiation without passing through an attenuating foil or window. 22. The method as set forth in claim 13 wherein the target nuclide is .sup.64 Ni and the target is irradiated with protons to form .sup.64 Cu according to the reaction .sup.64 Ni(p,n).sup.64 Cu. 23. The method as set forth in claim 14 wherein the amount of .sup.64 Cu produced is at least an amount sufficient for preparing a radiotherapeutic agent and the specific activity of the separated .sup.64 Cu is sufficient for clinical use in a radiotherapeutic agent. 24. The method as set forth in claim 14 wherein the target is irradiated for at least about 1/2 hour with a proton beam having a current sufficient to produce at least about 100 mCi of .sup.64 Cu in less than about 24 hours. 25. The method as set forth in claim 14 wherein the .sup.64 Ni comprises less than about 250 ppm by weight carrier copper, and the target is irradiated for at least about 1 hour with a proton beam having an energy ranging from about 5 MeV to about 25 MeV and a current sufficient to produce at least about 200 mCi of .sup.64 Cu in less than about 12 hours. 26. The method as set forth in claim 14 wherein the amount of .sup.64 Cu produced is at least about 10 mCi. 27. The method as set forth in claim 14 wherein the amount of .sup.64 Cu produced is at least about 100 mCi. 28. The method as set forth in claim 14 wherein the separated .sup.64 Cu has a specific activity of at least about 15 mCi/.mu.g Cu. 29. The method as set forth in claim 14 wherein the separated .sup.64 Cu has a specific activity of at least about 100 mCi/.mu.g Cu. 30. The method as set forth in claim 14 wherein the beam energy ranges from about 5 MeV to about 25 MeV. 31. The method as set forth in claim 30 wherein the beam current ranges from about 1 .mu.A to about 1 mA at about 5 MeV, to about 150 .mu.A at about 8 MeV, to about at 100 .mu.A at about 11 MeV, to about 60 .mu.A at about 25 MeV and to about 45 .mu.A at about 25 MeV. 32. The method as set forth in claim 14 wherein the target comprises a substrate and a target layer formed on a surface of the substrate, the target layer consisting essentially of isotopically enriched .sup.64 Ni and having a projected thickness of at least about 20 .mu.m, the substrate consisting essentially of an inert material having a thermal conductivity which is about equal to or greater than the thermal conductivity of .sup.64 Ni. 33. The method as set forth in claim 32 wherein the target layer is an electroplated target layer. 34. The method as set forth in claim 32 wherein the target layer consists essentially of .sup.64 Ni enriched to at least about 95% and has a projected thickness ranging from about 20 .mu.m to about 500 .mu.m, and the substrate consists essentially of gold and has a front surface, a back surface substantially parallel to and opposing the front surface and a thickness ranging from about 0.5 mm to about 2 mm. 35. The method as set forth in claim 32 wherein the .sup.64 Ni target is irradiated with a proton beam having an energy ranging from about 5 MeV to about 25 MeV, the method further comprising 36. The method as set forth in claim 14 wherein the target comprises a target layer formed over a surface of a substrate, the target layer including, after irradiation, .sup.64 cu, unreacted .sup.64 Ni and other radionuclides, and .sup.64 Cu is separated from unreacted .sup.64 Ni and from the substrate layer using a separation unit, the separation unit including a shielded housing that encloses components arranged to facilitate automatic and remote separation of the .sup.64 Cu, the components being selected from the group consisting of one or more fluid containers, an ion exchange column, and one or more pipetters in isolable fluid communication with the containers or the column, the .sup.64 Cu being separated by 37. The method as set forth in claim 36 wherein the pipetters include a plunger and the acid solution in the dissolution vessel is agitated while the irradiated target is exposed to the acid solution by effecting repetitive upward and downward movements of the pipetter plunger in fluid communication with the dissolution vessel. 38. The method as set forth in claim 14 further comprising, after the step of separating the radionuclide from unreacted target nuclide, recycling the unreacted .sup.64 Ni for use in preparing another target.