Isotope preparation method

Abstract

The present invention comprises a method for the generation of 227 Th of pharmaceutically tolerable purity comprising i) preparing a generator mixture comprising 227 Ac, 227 Th and 223 Ra; ii) loading said generator mixture onto a strong base anion exchange resin; iii) eluting a mixture of said 223 Ra and 227 Ac from said strong base anion exchange resin using a first mineral acid in an aqueous solution; iv) eluting 227 Th from said strong base anion exchange resin using a second mineral acid in an aqueous solution whereby to generate a first 227 Th solution containing contaminant 223 Ra and 227 Ac; v) loading the first 227 Th solution onto a strong acid cation exchange resin; vi) eluting at least a part of the contaminant 223 Ra and 227 Ac from said strong acid cation exchange resin using a third mineral acid in aqueous solution; and vii) eluting the 227 Th from said strong acid cation exchange resin using a first aqueous buffer solution to provide a second 227 Th solution. Purified thorium-227 of pharmaceutical purity and a pharmaceutical composition comprising the same are also provided.

1 ) A method for the generation of  227 Th of pharmaceutically tolerable purity comprising the steps of:
 i) preparing a generator mixture comprising  227 Ac,  227 Th and  223 Ra;   ii) loading said generator mixture onto a strong base anion exchange resin;   iii) eluting a mixture of said  223 Ra and  227 Ac from said strong base anion exchange resin using a first mineral acid in an aqueous solution;   iv) eluting  227 Th from said strong base anion exchange resin using a second mineral acid in an aqueous solution whereby to generate a first  227 Th solution containing contaminant  223 Ra and  227 Ac;   v) loading the first  227 Th solution onto a strong acid cation exchange resin;   vi) eluting at least a part of the contaminant  223 Ra and  227 Ac from said strong acid cation exchange resin using a third mineral acid in aqueous solution; and   vii) eluting the  227 Th from said strong acid cation exchange resin using a first aqueous buffer solution to provide a second  227 Th solution.   
     
     
         2 ) The method of  claim 1  additionally comprising the steps of:
 viii) loading the second  227 Th solution eluted in step vii) onto a second strong base anion exchange resin; 
 ix) eluting  223 Ra and/or  227 Ac from said second strong base anion exchange resin using a fourth mineral acid in an aqueous solution; and 
 x) eluting  227 Th from said second strong base anion exchange resin using a fifth mineral acid in an aqueous solution to provide a third  227 Th solution. 
 
     
     
         3 ) The method as claimed in  claim 1  wherein at least 99.9% of the  227 Ac loaded onto the resin in step ii) is eluted in step iii). 
     
     
         4 ) The method as claimed in  claim 1  wherein at least 70% of the  227 Th loaded onto the resin in step ii) is eluted in step vii). 
     
     
         5 ) The method of  claim 1  additionally comprising the step of:
 y) storing the  227 Ac eluted in step iii) for a period sufficient to allow ingrowth of  227 Th by radioactive decay, whereby to regenerate a generator mixture comprising  227 Ac,  227 Th and  223 Ra. 
 
     
     
         6 ) The method of  claim 1  wherein the method purifies sufficient  227 Th for more than 25 doses. 
     
     
         7 ) The method of  claim 1  wherein a  227 Th radioactivity of at least 50 MBq is employed in step i). 
     
     
         8 ) The method of  claim 2  wherein the strong base anion exchange resin and the second strong base anion exchange resin comprise the same base moieties. 
     
     
         9 ) The method of  claim 1  wherein the strong base anion exchange resin is a polystyrene/divinyl benzene copolymer based resin, preferably containing 1-95% DVB. 
     
     
         10 ) The method of  claim 1  wherein the strong base anion exchange resin and optionally the second strong base anion exchange resin is independently an R—N + Me 3  type (type I) resin or an R—N + Me 2 CH 2 CH 2 OH (Type II) resin. 
     
     
         11 ) The method of  claim 1  wherein the first mineral acid is an acid selected from H 2 SO 4 , HNO 3  and mixtures thereof and preferably comprises HNO 3 . 
     
     
         12 ) The method of  claim 1  wherein the first mineral acid is used at a concentration of 1 to 12 M. 
     
     
         13 ) The method of  claim 1  wherein the second mineral acid is an acid selected from H 2 SO 4  and HCl, preferably HCl. 
     
     
         14 ) The method of  claim 1  wherein the second mineral acid is used at a concentration of 0.1 to 8 M. 
     
     
         15 ) The method of  claim 1  wherein the strong acid cation exchange resin is a polystyrene/divinyl benzene copolymer based resin, preferably containing 1-95 DVB. 
     
     
         16 ) The method of  claim 1  wherein the strong acid cation exchange resin is of SO 3 H type. 
     
     
         17 ) The method of  claim 1  wherein the third mineral acid is an acid selected from H 2 SO 4 , HNO 3  and HCl, preferably HNO 3 . 
     
     
         18 ) The method of  claim 1  wherein the third mineral acid is used at a concentration of 0.1 to 8 M. 
     
     
         19 ) The method of  claim 1  wherein the buffer solution has a pH of between 2.5 and 6. 
     
     
         20 ) The method of  claim 1  wherein the buffer solution is an acetate buffer. 
     
     
         21 ) The method of  claim 1  wherein the buffer solution does not comprise any significant amount of any alcohol selected from methanol, ethanol and isopropanol. 
     
     
         22 ) The method of  claim 1  wherein the second  227 Th solution has a contamination level of no more than 200 Bq  227 Ac per 1 MBq  227 Th. 
     
     
         23 ) The method of  claim 1  wherein said generator mixture is dissolved in an alcoholic aqueous solution comprising a loading mineral acid prior to loading said generator mixture onto a strong base anion exchange resin in step ii). 
     
     
         24 ) The method of  claim 2  wherein step viii) comprises acidifying the second  227 Th solution prior to loading onto said second strong base resin. 
     
     
         25 ) The method of  claim 2  wherein said fourth mineral acid is an acid selected from H 2 SO 4 , HNO 3  and HCl, preferably HNO 3 . 
     
     
         26 ) The method of  claim 2  wherein said fourth mineral acid is used at a concentration of 1 to 12 M. 
     
     
         27 ) The method of  claim 1  wherein the fifth mineral acid is an acid selected from H 2 SO 4  and HCl, preferably HCl. 
     
     
         28 ) The method of  claim 1  wherein the fifth mineral acid is used at a concentration of 0.1 to 8 M. 
     
     
         29 )  227 Th comprising less than 5 Bq  227 Ac per 100 MBq  227 Th. 
     
     
         30 )  227 Th produced by a method of  claim 1  and which comprises less than 5 Bq  227 Ac per 100 MBq  227 Th. 
     
     
         31 ) A pharmaceutical composition comprising the  227 Th as claimed in  claim 29  and optionally at least one pharmaceutically acceptable diluent.