Cassette for stabilised radiolabelling reaction

Abstract

The present invention provides a method for the synthesis of an injectable composition comprising a [ 18 F]-labelled pyridaben derivative that is advantageous over prior methods. In particular, the method of the present invention comprises a method of radiosynthesis that permits a more facile purification using solid phase extraction (SPE).

1 - 27 . (canceled) 
     
     
         28 . A cassette for preparing an  18 F-labelled compound comprising:
 i) a vessel containing a precursor compound of Formula I:
   BTM-LINKER-LG  (I)
 
 wherein: 
 BTM is an analogue of pyridaben; 
 LINKER is an alkylene or an alkoxyalkylene; and, 
 LG is a sulfonate-containing leaving group; 
   ii) a vessel containing water;   iii) one or more SPE cartridges;   iv) a vessel containing a solution comprising an organic solvent;   v) a vessel containing a solution comprising ethanol;   vi) a vessel containing a hydrolyzing reagent;   vii) TEMPO contained in a vessel or contained in said vessel containing the precursor compound;   viii) a reaction vessel;   ix) means for eluting the vessel of (i) with a suitable source of  18 F;   x) means to transfer the precursor compound and suitable source of  18 F to the reaction vessel;   xi) means to transfer the crude reaction mixture to said one or more SPE cartridges, the crude reaction mixture comprising an  18 F labelled compound of Formula II:
   BTM-LINKER- 18 F  (II)
 
 wherein BTM and LINKER are defined for Formula I; 
   xii) means to selectively transfer said water, said solution comprising an organic solvent and said solution comprising ethanol to said one or more SPE cartridges; and,   xiii) means to transfer said purified compound of Formula II to a product collection vial.   
     
     
         29 . The cassette as defined in  claim 28  which further comprises a vial containing a hydrolyzing reagent. 
     
     
         30 . The cassette as defined in  claim 28 , wherein said precursor compound is a compound of Formula Ia: 
       
         
           
           
               
               
           
         
         and said  18 F-labelled compound is a compound of Formula IIa: 
       
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is an optionally substituted C 1-6  alkyl; 
         R 2  is hydrogen or halo; 
         W is an optionally substituted alkylene or heteroalkylene. 
       
     
     
         31 . The cassette as defined in  claim 30 , wherein R 1  is C 1-6  alkyl. 
     
     
         32 . The cassette as defined in  claim 30 , wherein R 1  is methyl, ethyl, propyl, n-butyl, s-butyl, or t-butyl. 
     
     
         33 . The cassette as defined in  claim 30 , wherein R 2  is halo. 
     
     
         34 . The cassette as defined in  claim 30 , wherein R 2  is chloro. 
     
     
         35 . The cassette as defined in  claim 30 , wherein W is heteroalkylene. 
     
     
         36 . The cassette as defined in  claim 30 , wherein W is alkoxyalkylene. 
     
     
         37 . The cassette as defined in  claim 28 , wherein said compound of Formula I is a compound of Formula Ib: 
       
         
           
           
               
               
           
         
         and said compound of Formula II is a compound of Formula IIb: 
       
       
         
           
           
               
               
           
         
         R 1  is an optionally substituted C 1-6  alkyl; 
         R 2  is hydrogen or halo; 
         LINKER is an alkylene or an alkoxyalkylene; and, 
         LG is a sulfonate-containing leaving group. 
       
     
     
         38 . The cassette as defined in  claim 28 , wherein said compound of Formula I is: 
       
         
           
           
               
               
           
         
         wherein LG is a sulfonate-containing leaving group; 
         and said compound of Formula II is: 
       
       
         
           
           
               
               
           
         
       
     
     
         39 . The cassette as defined in  claim 28 , wherein LG is selected from mesylate, tosylate, triflate, nosylate, or 1,2-cyclic sulfate. 
     
     
         40 . The cassette as defined in  claim 28 , wherein LG is tosylate. 
     
     
         41 . The cassette as defined in  claim 28 , wherein said precursor compound is dissolved in acetonitrile. 
     
     
         42 . The cassette as defined in  claim 28 , wherein said TEMPO is present in a molar ratio to the precursor compound of between 0.01:1 and 5:1. 
     
     
         43 . The cassette as defined in  claim 28 , wherein the starting radioactivity is at least 100 GBq. 
     
     
         44 . The cassette as defined in  claim 28 , wherein the starting radioactivity is between 100-1000 GBq. 
     
     
         45 . The cassette as defined in  claim 28 , wherein the starting radioactivity is between 100-750 GBq. 
     
     
         46 . The cassette as defined in  claim 28 , further comprising a solid phase extraction (SPE) unit for purification of said  18 F-labelled compound.