Method

Abstract

The present invention relates to new and improved methods of synthesizing radiolabelling agents which can be used to label biomolecules for use as radiopharmaceuticals. It further relates to certain novel radiolabelling agents and their use in such methods. PET imaging methods and methods of diagnosis employing such radiolabelling agents form a further aspect of the invention.

1 - 29 . (canceled) 
     
     
         30 . A compound of formula (I′) or formula (I″), or a salt thereof: 
       
         
           
           
               
               
           
         
         wherein L is a positively charged leaving group selected from —N(C 1-6  alkyl) 3   + , 
         1,4-diazabicyclo[2.2.2]octan-1-ium, and 1-(C 1-3  alkyl)-pyrrolidin-1-ium; 
         R′ is an electron-withdrawing group; and 
         L′ is 1,4-diazabicyclo[2.2.2]octan-1-ium or 1-(C 1-3  alkyl)-pyrrolidin-1-ium. 
       
     
     
         31 . The compound of  claim 30 , which is a compound of formula (I′) or a salt thereof. 
     
     
         32 . The compound of  claim 30 , which is a compound of formula (I″) or a salt thereof. 
     
     
         33 . The compound of  claim 30 , wherein R′ is —CF 3 , —CH 2 CF 3 , —CH(CF 3 ) 2 , —C(CF 3 ) 3 , or 
       
         
           
           
               
               
           
         
         where n is an integer from 1 to 5 and each Z is independently —F, —Cl, —NO 2 , or —CN. 
       
     
     
         34 . The compound of  claim 30 , wherein R′ is 
       
         
           
           
               
               
           
         
         where n is an integer from 1 to 5 and each Z is independently —F, —Cl, —NO 2 , or —CN. 
       
     
     
         35 . The compound of  claim 30 , which is a compound of formula (I n ): 
       
         
           
           
               
               
           
         
         where n is an integer from 1 to 5 and each Z is independently —F, —Cl, —NO 2 , or —CN. 
       
     
     
         36 . The compound of  claim 30 , which is a compound of general formula (I s ): 
       
         
           
           
               
               
           
         
         wherein L′ and R′ in said compound of general formula (I s ) are selected such that said compound is one of compounds (8) to (21): 
       
       
         
           
                 
                 
               
                     
                 
                     
                   R′ 
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                   L′ 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   (8) 
                   (9) 
                   (10) 
                   (11) 
                   (12) 
                   (13) 
                   (14) 
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   (15) 
                   (16) 
                   (17) 
                   (18) 
                   (19) 
                   (20) 
                   (21). 
                 
                     
                 
             
                
                
               
            
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         37 . The compound of  claim 30 , which is in the form of a trifluoromethanesulphonate salt. 
     
     
         38 . The compound of  claim 30 , which is 5-formyl-N,N,N-trimethylpyridin-2-aminium trifluoromethanesulfonate. 
     
     
         39 . The compound of  claim 30 , which is 1-methyl-1-(5-((2,3,5,6-tetrafluorophenoxy) carbonyl)pyridin-2-yl)pyrrolidin-1-ium trifluoromethanesulfonate.