Radiolabelling methods

Abstract

The invention relates to radiodiagnostic and radiotherapeutic agents, including biologically active vectors labelled with radionuclides. It further relates to methods and reagents labelling a vector such as a peptide comprising reaction of a compound of formula (I) with a compound of formula (II): or, a compound of formula (III) with a compound of formula (IV) in the presence of a Cu (I) catalyst. The resultant labelled conjugates are useful as diagnostic agents, for example, as radiopharmaceuticals more specifically for use in Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) or for radiotherapy.

What is claimed is: 
     
         1 . A method for labelling a vector comprising reaction of a compound of formula (I) with a compound of formula (II): 
       
         
           
           
               
               
           
         
       
       or,
 a compound of formula (III) with a compound of formula (IV) 
 
       
         
           
           
               
               
           
         
       
       in the presence of a Cu (I) catalyst, wherein:
 L1, L2, L3, and L4 are each Linker groups; 
 R* comprises a chelating agent of Formula X: 
 
       
         
           
           
               
               
           
         
       
       where:
 each R 1A , R 2A , R 3A  and R 4A  is independently an R A  group; 
 each R A  group is independently H or C 1-10  alkyl, C 3-10  alkylaryl, C 2-10  alkoxyalkyl, C 1-10  hydroxyalkyl, C 1-10  alkylamine, C 1-10  fluoroalkyl, or 2 or more R A  groups, together with the atoms to which they are attached form a carbocyclic, heterocyclic, saturated or unsaturated ring, 
 or a chelating agent of formula (i), (ii), (iii), (iv) or (v): 
 
       
         
           
           
               
               
           
         
       
       to give a conjugate of formula (V) or (VI) respectively: 
       
         
           
           
               
               
           
         
       
       wherein L1, L2, L3, L4, and R* are as defined above. 
     
     
         2 . A method according to  claim 1  wherein R* comprises a positron  11 C or  18 F. 
     
     
         3 . A method according to  claim 1  wherein the vector is a peptide, protein, hormone, cell, bacterium, virus, or small drug-like molecule. 
     
     
         4 . A method according to  claim 1  wherein the vector is Arg-Gly-Asp peptide. 
     
     
         5 . A method according to  claim 1  wherein the vector is a peptide comprising the fragment: 
       
         
           
           
               
               
           
         
       
     
     
         6 . A method according to  claim 1  wherein the vector is the peptide of formula (A): 
       
         
           
           
               
               
           
         
         wherein X 7  is either —NH 2  or 
       
       
         
           
           
               
               
           
         
       
       wherein a is an integer of from 1 to 10. 
     
     
         7 . A method according to  claim 1  wherein elemental copper is used as source of the Cu(I) catalyst. 
     
     
         8 - 18 . (canceled) 
     
     
         19 . The method according to  claim 2  wherein R* is  18 F. 
     
     
         20 . The method according to  claim 6  wherein a is 1.