High Specific Activity Preparation of F-18 Tetrafluoroborate

Abstract

Embodiments of the invention provide methods of synthesizing 18F-tetrafluoroborate (18F-TFB) via direct radiofluorination on boron trifluoride (BF3) to enhance both labeling yield and specific activity. Uses of 18F-TFB include imaging of thyroid or breast cancer, and imaging of thyroid, breast, stomach, salivary glands or kidney.

1 . A method for imaging of thyroid or breast cancer, the method comprising:
 imaging of thyroid or breast cancer using a high specific activity preparation of  18 F-tetrafluoroborate having at least 95% radiochemical purity.   
     
     
         2 . The method of  claim 1  wherein the  18 F-tetrafluoroborate is prepared by direct radiofluorination on boron trifluoride (BF 3 ) by reacting the BF 3  directly with  18 F-fluoride. 
     
     
         3 . The method of  claim 1  wherein the  18 F-tetrafluoroborate is prepared by: (a) reacting  18 F-fluoride with boron trifluoride (BF 3 ); and (b) isolating the  18 F-tetrafluoroborate from unreacted  18 F-fluoride and BF 3 . 
     
     
         4 . The method of  claim 3 , wherein the BF 3  in step (b) is provided in a solution of boron trifluoride-tetrahydrofuran (BF 3 -THF) complex in petroleum ether. 
     
     
         5 . The method of  claim 4 , wherein BF 3 -THF complex is filtered to remove TFB before reacting with  18 F-fluoride. 
     
     
         6 . The method of  claim 3 , wherein the column is washed after step (b) to remove unreacted BF 3  and residual solvent from the column. 
     
     
         7 . The method of  claim 1  wherein the  18 F-tetrafluoroborate ( 18 F-TFB) is prepared by: (a) trapping  18 F-fluoride on an anion exchange column; (b) reacting  18 F-fluoride with boron trifluoride (BF 3 ); and (c) isolating the  18 F-TFB from unreacted  18 F-fluoride and BF 3  from the anion exchange column, wherein the resultant  18 F-TFB has a specific activity of at least 5 GBq/μmol. 
     
     
         8 . The method of  claim 1 , wherein an effective dose of  18 F-tetrafluoroborate is about 0.036 mSv/MBq in males and about 0.064 mSv/MBq in females. 
     
     
         9 . The method of  claim 1 , wherein the  18 F-tetrafluoroborate has a specific activity of at least 5 GBq/μmol. 
     
     
         10 . The method of  claim 1 , wherein the  18 F-tetrafluoroborate has a specific activity of at least 8 GBq/μmol. 
     
     
         11 . A method for imaging of thyroid, breast, stomach, salivary glands or kidney, the method comprising:
 imaging of thyroid, breast, stomach, salivary glands or kidney using a high specific activity preparation of  18 F-tetrafluoroborate having at least 95% radiochemical purity.   
     
     
         12 . The method of  claim 11  wherein the  18 F-tetrafluoroborate is prepared by direct radiofluorination on boron trifluoride (BF 3 ) by reacting the BF 3  directly with  18 F-fluoride. 
     
     
         13 . The method of  claim 11  wherein the  18 F-tetrafluoroborate is prepared by: (a) reacting  18 F-fluoride with boron trifluoride (BF 3 ); and (b) isolating the  18 F-tetrafluoroborate from unreacted  18 F-fluoride and BF 3 . 
     
     
         14 . The method of  claim 13 , wherein the BF 3  in step (b) is provided in a solution of boron trifluoride-tetrahydrofuran (BF 3 -THF) complex in petroleum ether. 
     
     
         15 . The method of  claim 14 , wherein BF 3 -THF complex is filtered to remove TFB before reacting with  18 F-fluoride. 
     
     
         16 . The method of  claim 13 , wherein the column is washed after step (b) to remove unreacted BF 3  and residual solvent from the column. 
     
     
         17 . The method of  claim 11  wherein the  18 F-tetrafluoroborate ( 18 F-TFB) is prepared by: (a) trapping  18 F-fluoride on an anion exchange column; (b) reacting  18 F-fluoride with boron trifluoride (BF 3 ); and (c) isolating the  18 F-TFB from unreacted  18 F-fluoride and BF 3  from the anion exchange column, wherein the resultant  18 F-TFB has a specific activity of at least 5 GBq/μmol. 
     
     
         18 . The method of  claim 11 , wherein an effective dose of  18 F-tetrafluoroborate is about 0.036 mSv/MBq in males and about 0.064 mSv/MBq in females. 
     
     
         19 . The method of  claim 11 , wherein the  18 F-tetrafluoroborate has a specific activity of at least 5 GBq/μmol. 
     
     
         20 . The method of  claim 11 , wherein the  18 F-tetrafluoroborate has a specific activity of at least 8 GBq/μmol.