Method for purification of 225ac from irradiated 226ra-targets

Abstract

The present invention describes a method for purification of 225 Ac from irradiated 226 Ra-targets provided on support, comprising a leaching treatment of the 226 Ra-targets for leaching essentially the entirety of 225 Ac and 226 Ra with nitric or hydrochloric acid, followed by a first extraction chromatography for separating 225 Ac from 226 Ra and other Ra-isotopes and a second extraction chromatography for separating 225 Ac from 210 Po and 210 Pb. The finally purified 225 Ac can be used to prepare compositions useful for pharmaceutical purposes.

1 - 21 . (canceled) 
     
     
         22 . A method for purification of  225 Ac from irradiated  226 Ra-targets provided on a support, comprising the following steps:
 a) leaching  225 Ac and  226 Ra from one or more  226 Ra-targets with a nitric acid solvent or a hydrochloric acid solvent under refluxing conditions to generate one or more  225 Ac and  226 Ra containing extracts;   b) removing the hydrochloric acid if the solvent in step a) is a hydrochloric acid solvent and redissolving the resulting material in nitric acid;   c) concentrating the  225 Ac and  226 Ra containing extracts;   d) separating  225 Ac from  226 Ra and other Ra isotopes by means of at least one first extraction chromatography with a solid support material having a first extractant system coated thereon, comprising at least one compound in accordance with general formula I in at least one compound in accordance with general formula II,   
       
         
           
           
               
               
           
         
         wherein in formula I:
 R1, R2 independently is octyl, n-octyl, phenyl, or phenyl substituted with C 1  to C 3  alkyl; 
 R3, R4 independently is propyl, isopropyl, butyl, or isobutyl; 
 
         wherein in formula II:
 R5, R6, and R7 independently is C 2 -C 5  alkyl, in particular, butyl, or isobutyl; 
 
         e) allowing the  226 Ra to flow through and then eluting  225 Ac retained on the solid support with diluted nitric or hydrochloric acid; 
         f) separating  225 Ac from  210 Po and  210 Pb by means of at least one second extraction chromatography with a solid support material having a second extractant system coated thereon, comprising at least one compound in accordance with general formula III in at least one compound in accordance with general formula IV, 
       
       
         
           
           
               
               
           
         
         wherein in formula III:
 R8 and R9 independently is H, C 1 -C 6  alkyl, or t-butyl;
 and 
 
 
         wherein in formula IV:
 R10 is C 4 to C 12  alkyl; 
 
         g) using 2M HCl as mobile phase; and 
         h) recovering  225 Ac as a flow-through separately from  210 Po and  210 Pb, which are retained on the solid support. 
       
     
     
         23 . A method for purification of  225 Ac from irradiated  226 Ra-targets provided on a support, comprising the following steps:
 a) leaching  225 Ac and  226 Ra from one or more  226 Ra-targets with a nitric acid solvent or a hydrochloric acid solvent under refluxing conditions to generate one or more  225 Ac and  226 Ra containing extracts;   b) removing the hydrochloric acid if the solvent in step a) is a hydrochloric acid solvent and redissolving the resulting material in nitric acid;   c) concentrating the  225 Ac and  226 Ra containing extracts;   d) separating  225 Ac from  226 Ra and other Ra isotopes by means of at least one first extraction chromatography with a solid support material having a first extractant system coated thereon, comprising at least one compound in accordance with general formula IA,   
       
         
           
           
               
               
           
         
         wherein in formula IA:
 R1a, R2a, R3a, R4a independently is octyl or 2-ethylhexyl; 
 
         e) allowing the  226 Ra to flow through and then eluting  225 Ac retained on the solid support with nitric acid having a concentration between about 0.01M and about 0.3M or with hydrochloric acid having a concentration between about 0.05M and about 1M; 
         f) separating  225 Ac from  210 Po and  210 Pb by means of at least one second extraction chromatography with a solid support material having a second extractant system coated thereon, comprising at least one compound in accordance with general formula III in at least one compound in accordance with general formula IV, 
       
       
         
           
           
               
               
           
         
         wherein in formula III:
 R8 and R9 independently is H, C 1 -C 6  alkyl, or t-butyl;
 and 
 
 
         wherein in formula IV:
 R10 is C 4  to C 12  alkyl; 
 
         g) using 2M HCl as mobile phase; and 
         h) recovering  225 Ac as a flow-through separately from  210 Po and  210 Pb, which are retained on the solid support. 
       
     
     
         24 . A method for purification of  225 Ac from irradiated  226 Ra-targets provided on a support, comprising the following steps:
 a) leaching  225 Ac and  226 Ra from one or more  226 Ra-targets with a nitric acid solvent or a hydrochloric acid solvent under refluxing conditions to generate one or more  225 Ac and  226 Ra containing extracts;   b) removing the hydrochloric acid if the solvent in step a) is a hydrochloric acid solvent and redissolving the resulting material in nitric acid;   c) concentrating the  225 Ac and  226 Ra containing extracts;   d) separating  225 Ac from  226 Ra and other Ra isotopes by means of at least one first extraction chromatography with a solid support material having a first extractant system coated thereon, comprising at least one compound in accordance with general formula IB,   
       
         
           
           
               
               
           
         
         e) allowing the  226 Ra to flow through and then eluting  225 Ac retained on the solid support with nitric acid having a concentration between about 0.02 M and about 0.1 M; 
         f) separating  225 Ac from  210 Po and  210 Pb by means of at least one second extraction chromatography with a solid support material having a second extractant system coated thereon, comprising at least one compound in accordance with general formula III in at least one compound in accordance with general formula IV, 
       
       
         
           
           
               
               
           
         
         wherein in formula III:
 R8 and R9 independently is H, C 1 —C 6  alkyl, or t-butyl;
 and 
 
 
         wherein in formula IV:
 R10 is C 4 to C 12  alkyl; 
 
         g) using 2M HCl as mobile phase; and 
         h) recovering  225 Ac as a flow-through separately from  210 Po and  210 Pb which are retained on the solid support. 
       
     
     
         25 . The method of any one of  claims 22  to  24 , wherein the support is a metal, and is selected from the group consisting of Aluminum or Aluminum alloys, passivated Aluminum, anodized Aluminum, coated Aluminum, Aluminum coated with an element of a Platinum group, precious metals, elements from a Platinum group; and mixtures thereof. 
     
     
         26 . The method of any one of  claims 22  to  24 , wherein said nitric acid solvent in step a) has a concentration range of about 0.001 M to about 2 M. 
     
     
         27 . The method of any one of  claims 22  to  24 , wherein the extracts of step a) are pooled. 
     
     
         28 . The method of any one of  claims 22  to  24 , wherein the concentrating in step c) results in a  225 Ac and  226 Ra containing extract having a concentration of about 1.5 M to about 10 M of nitric acid. 
     
     
         29 . The method of  claim 22 , wherein the first extractant system is octyl(phenyl)-N,N-diisobutylcarbamoylphosphine oxide [CMPO] in tributyl phosphate [TBP]. 
     
     
         30 . The method of any one of  claims 22  to  24 , wherein the second extractant system is a crown ether in accordance with formula V: 
       
         
           
           
               
               
           
         
       
     
     
         31 . The method of any one of  claims 22  to  24 , wherein the second extractant system is 4,4′-bis(t-butylcyclohexano)-18-crown-6 in 1-octanol. 
     
     
         32 . The method of any one of  claims 22  to  24 , wherein the second extractant system is 4,5′-bis(t-butylcyclohexano)-18-crown-6 in 1-octanol. 
     
     
         33 . The method of any one of  claims 22  to  24 , wherein the first extraction chromatography of step d) is repeated one or more times. 
     
     
         34 . The method of any one of  claims 22  to  24 , wherein the second extraction chromatography of step f) is repeated one or more times. 
     
     
         35 . The method of any one of  claims 22  to  24 , further comprising removing Rn from the support or the  225 Ac and  226 Ra containing extract during step a). 
     
     
         36 . The method of  claim 35 , wherein the Rn is removed by means of a first alkaline trap to neutralize acidic vapours, a subsequent silica trap to absorb water, and a final activated coal trap. 
     
     
         37 . The method of any one of  claims 22  to  24 , further comprising a step of recovering a  226 Ra flowthrough of step e). 
     
     
         38 . The method of any one of  claims 22  to  24 , further comprising a step of eluting  210 Po from the solid support of the second extraction chromatography in step h) by means of concentrated nitric acid or concentrated hydrochloric acid. 
     
     
         39 . The method of any one of  claims 22  to  24 , wherein a fraction of a purification step is examined by means of α- and/or γ-spectroscopy. 
     
     
         40 . The method of any one of  claims 22  to  24 , wherein a fraction of a purification step containing any one of:
 a)  225 Ac; 
 b) Ra-isotopes; 
 c)  210 Po; and 
 d)  210 Pb 
 
       is subjected to an evaporation step. 
     
     
         41 . The method of any one of  claims 22  to  24 , further comprising a step of removing one or more organic impurities from a fraction of a purification step. 
     
     
         42 . A pharmaceutically acceptable  225 Ac-containing radionuclide composition obtained by the method of any one of  claims 22  to  24 . 
     
     
         43 . The method of any one of  claims 22  to  24 , wherein the nitric acid solvent of step a) has a concentration of about 0.1M. 
     
     
         44 . The method of any one of  claims 22  to  24 , wherein the hydrochloric acid solvent of step a) has a concentration of about 0.001 M to 2 M. 
     
     
         45 . The method of any one of  claims 22  to  24 , wherein the nitric acid solvent or the hydrochloric acid solvent of step a) is used at a temperature of about 30 to 90° C. 
     
     
         46 . The method of  claim 36 , wherein the activated coal trap is cooled. 
     
     
         47 . The method of any one of  claims 22  to  24 , further comprising a step of eluting  210 Pb from the solid support of the second extraction chromatography in step h) by means of concentrated hydrochloric acid or EDTA. 
     
     
         48 . The method of  claim 40 , wherein the fraction is evaporated to a wet or a dry residue. 
     
     
         49 . The method of  claim 40 , wherein the fraction is redissolved. 
     
     
         50 . The method of  claim 41 , wherein the step of removing one or more organic impurities from a fraction of a purification step is performed by passing the fraction through a resin comprising a non-ionic acrylic ester polymer.