Medical radioisotopes and methods for producing the same

Abstract

This disclosure concerns a new method for preparing technetium-99 m , via its molybdenum-99 parent, by alpha particle irradiation of zirconium-96. Also disclosed are novel compositions containing one or more of technetium-99 m , molybdenum-99 and zirconium species. Systems for producing molybdenum-99 and technetium-99 m , including alpha particle generators and irradiation targets, also are described herein.

1 . A system for producing molybdenum-99, comprising: 
 an alpha particle source for producing an alpha particle beam having a beam diameter and a beam axis; and    a target comprising zirconium-96 arranged such that at least a portion of the alpha particle beam intersects the target, the target capable of producing an irradiated material comprising molybdenum-99 when the target is exposed to the alpha particle source.    
   
   
       2 . The system according to  claim 1 , wherein the target is enriched in zirconium-96.  
   
   
       3 . The system according to  claim 2 , wherein the target has a zirconium-96 concentration of at least about 10%.  
   
   
       4 . The system according to  claim 2 , wherein the target has a zirconium-96 concentration of at least about 50%.  
   
   
       5 . The system according to  claim 2 , wherein the target has a zirconium-96 concentration of at least about 90%.  
   
   
       6 . The system according to  claim 2 , wherein the target has a zirconium-96 concentration of about 95%.  
   
   
       7 . The system according to  claim 1 , wherein the target has a thickness when positioned substantially parallel relative to the beam axis of from about 0.05 mm to about 1 mm.  
   
   
       8 . The system according to  claim 1 , wherein the target has a width when positioned substantially perpendicular relative to the beam axis of less than about the beam diameter.  
   
   
       9 . The system according to  claim 1 , wherein the target comprises a disk, a ribbon, a wire or combinations thereof.  
   
   
       10 . The system according to  claim 9 , wherein the disk is rotatable relative to the beam axis.  
   
   
       11 . The system according to  claim 10 , wherein the disk has a diameter of from about 1 to about 30 cm.  
   
   
       12 . The system according to  claim 1 , further comprising a bath for harvesting irradiated material from the target.  
   
   
       13 . The system according to  claim 1 , further comprising a focused ion beam source for removing irradiated material from the target.  
   
   
       14 . The system according to  claim 1 , further comprising means for removing irradiated material from the target.  
   
   
       15 . The system according to  claim 1 , wherein the alpha particle source is a table-top generator.  
   
   
       16 . The system according to  claim 14 , wherein the target has a thickness such that it can be irradiated to a depth of at least about 100 μms to produce molybdenum-99, irradiated material on the target harvested, and unexposed target material irradiated a second time to produce molybdenum-99.  
   
   
       17 . The system according to  claim 1 , wherein the alpha particle source is a cyclotron.  
   
   
       18 . The system according to  claim 1 , wherein the alpha particle source is an accelerator.  
   
   
       19 . The system according to  claim 1 , wherein the alpha particle beam has a flux of at least about 10 16  α/(cm 2 )s.  
   
   
       20 . The system according to  claim 1 , wherein the alpha particle beam has an energy of from about 10 to about 30 MeV.  
   
   
       21 . The system according to  claim 1 , wherein the alpha particle beam has an energy distribution centered at about 15 MeV.  
   
   
       22 . The system according to  claim 1 , wherein the alpha particle beam is substantially monoenergetic having an energy of about 15 MeV.  
   
   
       23 . A process for producing molybdenum-99, comprising: 
 providing a zirconium target; and    irradiating at least a portion of the target with alpha particles, thereby producing an irradiated target portion comprising molybdenum-99.    
   
   
       24 . The process according to  claim 23 , further comprising separating the molybdenum-99 from other target species.  
   
   
       25 . The process according to  claim 24 , wherein separating comprises chemical separation.  
   
   
       26 . The process according to  claim 25 , wherein separating comprises mass difference separation.  
   
   
       27 . The process according to  claim 26 , wherein the mass difference separation comprises plasma separation.  
   
   
       28 . The process according to  claim 23 , further comprising removing at least a part of the irradiated target portion from the target.  
   
   
       29 . The process according to  claim 23 , wherein removing comprises contacting the irradiated target portion with a solvent thereby producing an irradiated target solution.  
   
   
       30 . The process according to  claim 29 , wherein the solvent is aqua regia.  
   
   
       31 . The process according to  claim 30 , further comprising evaporating the aqua regia, thereby yielding a residue comprising zirconium and molybdenum-99.  
   
   
       32 . The process according to  claim 31 , further comprising contacting the residue with an alkaline solution to selectively dissolve molybdenum species.  
   
   
       33 . The process according to  claim 23 , wherein the irradiating at least a portion of the target includes exposing the target to an alpha particle beam having a flux of at least about 10 16  α/(cm 2 )s.  
   
   
       34 . The process according to  claim 30 , further comprising adjusting the concentration of the irradiated target solution to a chloride molarity of from about 4 to about 8 and subjecting the solution to ion exchange chromatography.  
   
   
       35 . The process according to  claim 23 , further comprising contacting the target with a fluoridating agent.  
   
   
       36 . The process according to  claim 35 , wherein contacting the irradiated target with the fluoridating agent produces fluoride species comprising MoF 5 , MoF 6  or both.  
   
   
       37 . The process according to  claim 36 , wherein the fluoridating agent comprises at least one of NF 3  and HF.  
   
   
       38 . The process according to  claim 36 , wherein contacting the irradiated target with the fluoridating agent comprises activating the fluoridating agent with microwave radiation.  
   
   
       39 . The process according to  claim 28 , wherein removing at least a part of the irradiated target portion from the target comprises sputtering.  
   
   
       40 . The process according to  claim 39 , wherein sputtering employs a focused ion beam.  
   
   
       41 . The process according to  claim 28 , wherein removing at least a part of the irradiated target portion from the target comprises mechanical milling.  
   
   
       42 . The process according to  claim 28 , wherein removing and irradiating are performed in a continuous process.  
   
   
       43 . Molybdenum-99 produced by the process of  claim 23 .  
   
   
       44 . A technetium generator comprising molybdenum-99 produced by the process of  claim 23 .  
   
   
       45 . A process for producing technetium-99m, comprising: 
 providing a zirconium target comprising at least about 50% zirconium-96; and    irradiating the zirconium target with alpha particles, thereby producing an irradiated target comprising molybdenum-99.    
   
   
       46 . The process according to  claim 45 , further comprising purifying the molybdenum-99 to produce purified molybdenum-99.  
   
   
       47 . The process according to  claim 46 , further comprising loading the purified molybdenum-99 onto an adsorbent column.  
   
   
       48 . The process according to  claim 47 , further comprising allowing at least a portion of the purified molybdenum-99 to decay to technetium-99m.  
   
   
       49 . The process according to  claim 48 , further comprising eluting the technetium-99m from the adsorbent column.  
   
   
       50 . Technetium-99m produced by the process of  claim 49 .  
   
   
       51 . A process, comprising: 
 providing a target comprising zirconium;    irradiating the target;    removing a portion of the target including molybdenum-99 formed during irradiation; and    irradiating a remaining unexposed portion of the target.    
   
   
       52 . The process according to  claim 51 , further comprising purifying molybdenum-99 from the removed portion of the target.  
   
   
       53 . The process according to  claim 52 , wherein purifying molybdenum-99 comprises ion-exchange chromatography.  
   
   
       54 . The process according to  claim 52 , wherein purifying molybdenum-99 comprises selectively dissolving molybdenum-99 in a solvent.  
   
   
       55 . The process according to  claim 52 , wherein purifying molybdenum-99 comprises forming a molybdenum fluoride.  
   
   
       56 . A medical radioisotope composition consisting essentially of zirconium and molybdenum-99.  
   
   
       57 . A composition comprising at least one molybdenum fluoride, wherein the molybdenum fluoride comprises molybdenum-99.  
   
   
       58 . The composition according to  claim 57  wherein the molybdenum fluoride comprises at least about 80% molybdenum-99.  
   
   
       59 . The composition according to  claim 57 , wherein the molybdenum fluoride comprises at least about 90% molybdenum-99.  
   
   
       60 . The medical radioisotope composition according to  claim 56 , further comprising a carrier.  
   
   
       61 . A medical radioisotope composition, comprising molybdenum-99, wherein the medical radioisotope composition has an SPA value of at least about 19.2×10 4  Ci/gm at discharge.  
   
   
       62 . The medical radioisotope composition according to  claim 61 , wherein the medical radioisotope composition has an SPA value of at least about 38×10 4  Ci/gm at discharge.  
   
   
       63 . A medical radioisotope composition, comprising molybdenum-99, wherein the composition is substantially free of actinides.  
   
   
       64 . The medical radioisotope composition according to  claim 61 , wherein the medical radioisotope composition is substantially free of radioactive isotopes of strontium, ruthenium, tellurium and iodine.  
   
   
       65 . The medical radioisotope composition according to  claim 61 , further comprising a carrier.  
   
   
       66 . The medical radioisotope composition according to  claim 65 , wherein the carrier comprises saline.  
   
   
       67 . The medical radioisotope composition according to  claim 61 , further comprising a technetium generator.  
   
   
       68 . A medical radioisotope composition, comprising: 
 molybdenum-99;    at least one of molybdenum-93m and niobium-96; and    a carrier.    
   
   
       69 . The medical radioisotope composition according to  claim 68 , wherein the carrier is saline.  
   
   
       70 . The medical radioisotope composition according to  claim 68 , contained in a technetium generator.  
   
   
       71 . A zirconium target for the production of molybdenum-99, comprising a zirconium disk, the disk being mounted on a spindle, such that the disk is rotatable about an axis substantially parallel to the disk's smallest dimension, wherein the zirconium disk is capable of producing molybdenum-99 when irradiated with an alpha particle source.  
   
   
       72 . The zirconium target according to  claim 71 , wherein the target is enriched in zirconium-96.  
   
   
       73 . The zirconium target according to  claim 71 , wherein the spindle is electrically connected to the disk and to ground.  
   
   
       74 . A target for the production of molybdenum-99, comprising a substrate and a coating comprising zirconium-96, wherein the target is capable of producing molybdenum-99 when irradiated with an alpha particle source.  
   
   
       75 . The target according to  claim 74 , further comprising an interlayer between the coating and the substrate.  
   
   
       76 . The target according to  claim 74 , wherein the coating is enriched in zirconium-96.  
   
   
       77 . The target according to  claim 74 , wherein the coating has a thickness of from about 200 μm to about 1 cm.  
   
   
       78 . The target according to  claim 74 , wherein the coating is sputter-coated on the substrate.