Radiotracer compositions and methods

Abstract

The present invention relates to the field of radiopharmaceuticals for in vivo imaging, in particular to radiotracer compositions which comprises 18F-labelled c-Met binding peptides. The invention provides said compositions, as well as associated automated methods of preparation and cassettes.

1 - 17 . (canceled) 
     
     
         18 . A method of preparation of a radiopharmaceutical composition comprising:
 (A) reacting a first non-radioactive precursor with [ 18 F]-fluoride to give [ 18 F]-fluorobenzaldehyde in a single-use cassette comprising:
 (i) a first non-radioactive precursor, capable of reacting with [ 18 F]-fluoride to give [ 18 F]-fluorobenzaldehyde; 
 (ii) a second non-radioactive precursor of Formula III: 
   
       
         
           
           
               
               
           
         
         wherein C a , C b , C c , and C d  in Formula III are each cysteine residues such that residues C a  and C b  as well as C c  and C d  are cyclized to form two separate disulfide bonds; 
         (iii) a reverse phase solid phase extraction column; 
         (iv) a supply of the radioprotectant; 
         (v) a reaction vessel; 
         (vi) at least one suitable solvent; 
         (B) reacting the [ 18 F]-fluorobenzaldehyde from step (A) with the second non-radioactive precursor to give a radiotracer of Formula II in a crude radiotracer solution: 
       
       
         
           
           
               
               
           
         
         wherein C a , C b , C c , and C d  in Formula II are each cysteine residues such that residues C a  and C b  as well as C c  and C d  d are cyclized to form two separate disulfide bonds; 
         (C) adding said radioprotectant to the crude radiotracer solution from step (B); 
         (D) purifying the radiotracer solution from step (C) using said reverse phase solid phase extraction column to give a purified [ 18 F]-radiotracer solution; 
         (E) optionally diluting the purified [ 18 F]-radiotracer solution from step (D) with a biocompatible carrier; 
         (F) filtering the optionally diluted purified [ 18 F]-radiotracer solution from step (E) to give said radiopharmaceutical composition; 
         wherein said cassette fits removably and interchangeably onto an automated synthesizer apparatus and at least steps (A)-(D) are carried out in the automated synthesizer apparatus. 
       
     
     
         19 . The method of  claim 18 , where the steps (A)-(F) are carried out in the automated synthesizer apparatus. 
     
     
         20 . The method of  claim 18 , where the radiotracer solution of step (C) comprises said radiotracer in aqueous acetonitrile of 5 to 25% v/v acetonitrile. 
     
     
         21 . The method of  claim 20 , where the radiotracer solution of step (C) further comprises 0.5 to 5% v/v ethanol. 
     
     
         22 . The method of  claim 18 , where the purification step (D) is carried out as follows:
 (i) passing the purified [ 18 F]-radiotracer solution from step (D) through said reverse phase SPE cartridge, wherein the radiotracer is retained on said SPE cartridge;   (ii) washing the SPE cartridge from step (i) one or more times with a wash solution which comprises an aqueous acetonitrile solution of said radioprotectant of 15 to 25% v/v acetonitrile content;   (iii) washing the SPE cartridge from step (ii) one or more times with water or aqueous buffer solution;   (iv) eluting the washed SPE cartridge of step (ii) or (iii) with an elution solvent which comprises said radioprotectant in an aqueous ethanol solution having an ethanol content of 35 to 80% v/v,   
       wherein the eluent comprises purified radiotracer in said elution solvent. 
     
     
         23 . The method of  claim 18 , wherein the SPE cartridge is a C 18  SPE cartridge. 
     
     
         24 . The method of  claim 23 , where the elution solvent of step (iv) comprises 40-60% v/v aqueous ethanol. 
     
     
         25 . The method of  claim 23 , which further comprises:
 (G) dispensing the [ 18 F]-radiotracer radiopharmaceutical composition of step (F) into one or more syringes.   
     
     
         26 . A single-use cassette comprising:
 a first non-radioactive precursor, capable of reacting with [ 18 F]-fluoride to give [ 18 F]-fluorobenzaldehyde;   a second non-radioactive precursor of Formula III:   
       
         
           
           
               
               
           
         
         wherein C a , C b , C c , and C d  in Formula III are each cysteine residues such that residues C a  and C b  as well as C c  and C d  are cyclized to form two separate disulfide bonds; 
         a reverse phase solid phase extraction column; 
         a supply of radioprotectant; 
         a reaction vessel; and 
       
       at least one suitable solvent.