Eluent solution

Abstract

The present invention provides a novel method for the preparation of 18F-fluoride (18F) for use in radiofluorination reactions. The method of the invention finds use especially in the preparation of 18F-labelled positron emission tomography (PET) tracers. The method of the invention is particularly advantageous where bulk solutions are prepared and stored in prefilled vials rather than being freshly prepared on the day of synthesis. Also provided by the present invention is a radiofluorination reaction which comprises the method of the invention, as well as a cassette for use in carrying out the method of the invention and/or the radiofluorination method of the invention on an automated radiosynthesis apparatus.

1 - 26 . (canceled) 
     
     
         27 . A radiotracer composition comprising a purified reaction mixture of the  18 F-FACBC made according to the process comprising:
 (a) reacting in a reaction vessel of the cassette system a source of  18 F-fluoride with a precursor compound of Formula I:   
       
         
           
           
               
               
           
         
         wherein: 
         LG is a leaving group; 
         PG 1  is a carboxy protecting group; 
         and, PG 2  is an amine protecting group; 
         to obtain a reaction mixture comprising a compound of Formula II: 
       
       
         
           
           
               
               
           
         
       
       wherein PG 1  and PG 2  are as defined for Formula I;
 (b) removing PG 1  to obtain a reaction mixture comprising a compound of Formula III: 
 
       
         
           
           
               
               
           
         
         wherein PG 1  is as defined for Formula I; 
         (c) removing PG 2  to obtain a reaction mixture comprising anti-1-amino-3- 18 F-fluorocyclobutyl-1-carboxylic acid ( 18 F-FACBC); and 
         (d) purifying said reaction mixture comprising  18 F-FACBC by passing it through only one solid phase extraction cartridge of the cassette system, wherein the solid phase extraction cartridge is a hydrophilic lipophilic balanced (HLB) solid phase extraction cartridge. 
       
     
     
         28 . The radiotracer composition of  claim 27 , further comprising a citrate buffer in a concentration range of 50-100 mM and a pH of 4.0-5.0. 
     
     
         29 . The radiotracer composition of  claim 27 , further comprising a citrate buffer in a concentration range of 60-90 mM and a pH of 4.0-5.0. 
     
     
         30 . The radiotracer composition of  claim 27 , further comprising a citrate buffer in a concentration range of 75-85 mM and a pH of 4.0-5.0. 
     
     
         31 . The radiotracer composition of  claim 27 , wherein the composition lacks breakthrough aluminum. 
     
     
         32 . The radiotracer composition of  claim 27 , with the proviso that said composition does not comprise a radiostabilizer. 
     
     
         33 . The radiotracer composition of  claim 27 , with the proviso that said composition does not comprise a sugar lactone or a sugar alcohol. 
     
     
         34 . An aqueous pharmaceutical radiotracer composition comprising:
 an  18 F-FACBC radiotracer; and   a citrate buffer, the citrate buffer being present in said aqueous pharmaceutical radiotracer composition at a concentration of 50-100 mM, wherein the aqueous pharmaceutical radiotracer composition has a pH of 4.0-5.0 and lacks breakthrough aluminum.   
     
     
         35 . The radiotracer composition of  claim 34 , wherein the concentration of the citrate buffer is in a range of 60-90 mM. 
     
     
         36 . The radiotracer composition of  claim 34 , wherein the concentration of the citrate buffer is in a range of 75-85 mM. 
     
     
         37 . The radiotracer composition of  claim 34  that has an end of synthesis (EOS) radioactive concentration (RAC) of at least 1000 MBq/mL. 
     
     
         38 . The radiotracer composition of  claim 34  that has an end of synthesis (EOS) radioactive concentration (RAC) of at least 1500 MBq/ml. 
     
     
         39 . The radiotracer composition of  claim 34  which comprises not more than 150 μg/mL 1-amino-3-hydroxyl-cyclobutane-1-carboxylic acid (hydroxyl-ACBC). 
     
     
         40 . The radiotracer composition of  claim 34 , which comprises not more than 80 μg/mL hydroxyl-ACBC. 
     
     
         41 . The radiotracer composition of  claim 34 , which comprises not more than 2.0 μg/mL 1-amino-3-chloro-cyclobutane-1-carboxylic acid (chloro-ACBC). 
     
     
         42 . The radiotracer composition of  claim 34 , which comprises not more than 1.0 μg/mL chloro-ACBC.