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 a 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 . Method for purification of  225 Ac from irradiated  226 Ra-targets provided on a support, comprising the following steps:
 a) at least one leaching treatment of the  226 Ra-targets for leaching essentially the entirety of  225 Ac and  226 Ra with nitric or hydrochloric acid under refluxing conditions;   b) removing HCl if the solvent in step b) is hydrochloric acid 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) eluting  225 Ac which is retained on the solid support from the stationary phase with diluted nitric or hydrochloric acid, whereas  226 Ra is passing through; 
         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 from the flow-through, whereas  210 Po and  210 Pb are retained on the solid support. 
       
     
     
         2 . Method for purification of  225 Ac from irradiated  226 Ra-targets provided on a support, comprising the following steps:
 a) at least one leaching treatment of the  226 Ra-targets for leaching essentially the entirety of  225 Ac and  226 Ra with nitric or hydrochloric acid under refluxing conditions;   b) removing HCl if the solvent in step b) is hydrochloric acid 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) eluting  225 Ac which is retained on the solid support from the stationary phase with nitric acid within a concentration range of 0.3 M to 0.01 M or 1 M to 0.05 M hydrochloric acid, whereas  226 Ra is passing through; 
         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 from the flow-through, whereas  210 Po and  210 Pb are retained on the solid support. 
       
     
     
         3 . Method for purification of  225 Ac from irradiated  226 Ra-targets provided on a support, comprising the following steps:
 a) at least one leaching treatment of the  226 Ra-targets for leaching essentially the entirety of  225 Ac and  226 Ra with nitric or hydrochloric acid under refluxing conditions;   b) removing HCl if the solvent in step b) is hydrochloric acid 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 a compound in accordance with formula IB,   
       
         
           
           
               
               
           
         
         e) eluting  225 Ac which is retained on the solid support from the stationary phase with nitric acid having a concentration lower than appr. 0.1 M and higher then appr. 0.02 M, whereas  226 Ra is passing through; 
         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 from the flow-through, whereas  210 Po and  210 Pb are retained on the solid support. 
       
     
     
         4 . Method according to  claims 1  to  3 , wherein the support is selected from the group consisting of metals, in particular Aluminum or Aluminum alloys, passivated Aluminum, anodized Aluminum, coated Aluminum, Aluminum coated with an element of the Platinum group; precious metals, in particular elements from the Platinum group; and mixtures thereof. 
     
     
         5 . Method according to  claims 1  to  4 , wherein said nitric acid in step
 a) has a concentration range of appr. 0.001 M to 2 M, preferably appr. 0.1 M and said hydrochloric acid has a concentration range of 0.001 M to 2 M, and/or said acids are used at elevated temperatures, in particular, from appr. 30 to 90° C.   
     
     
         6 . Method according to  claims 1  to  5 , wherein extracts from the leaching treatment are pooled. 
     
     
         7 . Method according to  claims 1  to  6 , wherein in step c) a final concentration of 1.5 M to 10 M of nitric acid is achieved; 
     
     
         8 . Method according to  claim 1 , wherein the first extractant system is octyl(phenyl)-N,N-diisobutylcarbamoylphosphine oxide [CMPO] in tributyl phosphate [TBP]. 
     
     
         9 . Method according to  claims 1  to  3 , wherein the second extractant system is a crown ether in accordance with formula V: 
       
         
           
           
               
               
           
         
         in 1-octanol. 
       
     
     
         10 . Method according to  claim 9 , wherein the second extractant system is 4,4′-bis(t-butylcyclohexano)-18-crown-6 in 1-octanol. 
     
     
         11 . Method according to  claim 9 , wherein the second extractant system is 4,5′-bis(t-butylcyclohexano)-18-crown-6 in 1-octanol. 
     
     
         12 . Method according to any one of the preceding claims, wherein the first extraction chromatography of step d) is repeated several times, in order to remove trace amounts of Ra-isotopes, depending on the desired purity of the  225 Ac. 
     
     
         13 . Method according to any one of the preceding claims, wherein the second extraction chromatography of step f) is repeated several times, depending on the desired purity of the  225 Ac. 
     
     
         14 . Method according to any one of the preceding claims, wherein Radon which is contained in an Al-support and/or in the converted products is removed from the  225 Ac products and the Al-support during the leaching process by means of suitable traps. 
     
     
         15 . Method according to  claim 14 , wherein Rn is guided into a first alkaline trap to neutralize acidic vapours, into a subsequent silica trap to absorb water, and into a final activated coal trap, wherein the activated coal trap is optionally cooled. 
     
     
         16 . Method according to any one of the preceding claims, wherein  226 Ra is recovered from the flow-through of step e). 
     
     
         17 . Method according to any one of the preceding claims, wherein  210 Po is eluted from the solid support of the second extraction chromatography in step h) by means of concentrated nitric acid or concentrated hydrochloric acid, and  210 Pb is eluted with concentrated hydrochloric acid or EDTA solution. 
     
     
         18 . Method according to any one of the preceding claims, wherein each purification step and/or fraction is checked by means of α- and/or γ-spectroscopy. 
     
     
         19 . Method according to any one of the preceding claims, wherein respective fractions containing:
 a)  225 Ac; or   b) Ra-isotopes; or   c)  210 Po; and   d)  210 Pb   are evaporated to wet or dry residues and redissolved, if necessary.   
     
     
         20 . Method according to any one of the preceding claims, wherein organic impurities are removed, preferably by passing through a resin which contains a non-ionic acrylic ester polymer. 
     
     
         21 . Pharmaceutically acceptable  225 Ac-containing radionuclide composition obtainable by a method in accordance with at least one of  claims 1  to  20 .