Radioflorination methods

Abstract

The present invention relates to methods and reagents for [ 18 F]-fluorination, particularly of peptides. The resultant 18 F-labelled compounds are useful as radiopharmaceuticals, specifically for use in Positron Emission Tomography (PET). Thus, a compound of formula 18 F-(Linker)-SH, such as a compound of formula (IV), (V), or (VI): may be reacted with an activated peptide as a means for 18 F-labelling.

1 .- 3 . (canceled) 
     
     
         4 . A compound of formula (IV):
     18 F—(CH 2 CH 2 O) n —(CH 2 ) m —SH  (IV)   
       or a thiol protected precursor thereof, wherein:
 n is an integer of 1 to 20; 
 m is an integer of 1 to 10. 
 
     
     
         5 . A compound of formula (V):
     18 F—(CH 2 ) p —SH  (V)   
       or a thiol protected precursor thereof, wherein p is an integer of 1 to 20. 
     
     
         6 . A compound of formula (VI): 
       
         
           
           
               
               
           
         
       
       or a thiol protected precursor thereof, wherein:
 q is an integer of 0 to 4; and 
 r is an integer of 1 to 10. 
 
     
     
         7 . A compound of formula (VII), (VIII), or (IX): 
       
         
           
           
               
               
           
         
       
       wherein:
 n is an integer of 1 to 20; and 
 m is an integer of 1 to 10. 
 p is an integer of 1 to 20. 
 q is an integer of 0 to 4; and 
 r is an integer of 1 to 10. 
 
     
     
         8 . A compound of formula (X), (XI), or (XII): 
       
         
           
           
               
               
           
         
       
       wherein:
 n is an integer of 1 to 20; 
 m is an integer of 1 to 10; 
 p is an integer of 1 to 20; 
 q is an integer of 0 to 4; 
 r is an integer of 1 to 10; and 
 Y is a C 1-10  hydrocarbyl group optionally including 1 to 6 heteroatoms. 
 
     
     
         9 . A compound of formula (XII) according to  claim 8  which is: 
       
         
           
           
               
               
           
         
       
     
     
         10 . A radiofluorination kit comprising:
 (i) a compound of formula (IIa)
   L-(Linker)-SR  (IIa) 
   wherein L is a leaving group such as p-toluenesulphonate, trifluoromethanesulphonate, or methanesulphonate,   the Linker is a C 1-30  hydrocarbyl group optionally including 1 to 10 heteroatoms;   R is hydrogen or a thiol protecting group; and   (ii) an activated peptide of formula (I) or (Ia).   
       
         
           
           
               
               
           
         
       
     
     
         11 . A radiofluorination kit according to  claim 10 , comprising:
 (i) a compound of formula (IVa), (Va), or (VIa):   
       
         
           
           
               
               
           
         
         n is an integer of 1 to 20; 
         m is an integer of 1 to 10; 
         p is an integer of 1 to 20; 
         q is an integer of 0 to 4; 
         r is an integer of 1 to 10; 
         L is a leaving group such as p-toluenesulphonate, trifluoromethanesulphonate, or methanesulphonate; 
         L′ is a leaving group such as iodo, p-toluenesulphonate, trifluoromethanesulphonate, or methanesulphonate and when q is 0, L′ can be nitro or an iodonium or ammonium salt, 
         R is hydrogen or a thiol protecting group; and 
         (ii) an activated peptide of formula (I) or (Ia).