Stabilization of radiopharmaceutical compositions using ascorbic acid

Abstract

Radiopharmaceutical compositions, and related methods, useful for medical imaging are provided. The radiopharmaceutical compositions include one or more radiopharmaceutical compounds, together with a stabilizer comprising ascorbic acid, wherein the pH of said composition is within the range of about 3.5-5.5.

What is claimed is: 
     
         1 - 39 . (canceled) 
     
     
         40 . A composition, comprising:
 one or more radiopharmaceutical compounds of formula:   
       
         
           
           
               
               
           
         
       
       wherein:
 X is O, S, or NR; 
 Y is O, S, NR, or CH 2 ; 
 R is H or Me; 
 m is 0, 1, 2, or 3; 
 n is 0, 1, 2, or 3; and 
 R 1  and R 2  are hydrogen or C 1-10 -alkyl, 
 
       together with a stabilizer comprising ascorbic acid,
 wherein the pH of said composition is within the range of 3.5 to less than 6; and 
 wherein the composition comprises greater than 20 mg of ascorbic acid per milliliter. 
 
     
     
         41 . The composition of  claim 40 , wherein the composition comprises 2-tert-butyl-4-chloro-5-[4-(2-[ 18 F]fluoro-ethoxymethyl)-benzyloxy]-2H-pyridazin-3-one: 
       
         
           
           
               
               
           
         
       
       together with a stabilizer comprising ascorbic acid,
 wherein the pH of said composition is within the range of 3.5 to less than 6, and 
 wherein the composition comprises greater than 40 mg of ascorbic acid per milliliter. 
 
     
     
         42 . The composition of  claim 40 , wherein said pH is within the range of 5.5 to less than 6, or wherein said pH is 5.8. 
     
     
         43 . The composition of  claim 40 , wherein said radiopharmaceutical compound is 2-tert-butyl-4-chloro-5-[4-(2-[ 18 F]fluoro-ethoxymethyl)-benzyloxy]-2H-pyridazin-3-one: 
       
         
           
           
               
               
           
         
       
     
     
         44 . The composition of  claim 40 , wherein the composition comprises greater than 30 mg of ascorbic acid per milliliter, or greater than 40 mg of ascorbic acid per milliliter, or greater than 50 mg of ascorbic acid per milliliter, or greater than 100 mg of ascorbic acid per milliliter, or greater than 200 mg of ascorbic acid per milliliter, or between 50 and 200 mg of ascorbic acid per milliliter, or between 50 and 500 mg of ascorbic acid per milliliter. 
     
     
         45 . The composition of  claim 40 , wherein the composition comprises greater than 40 mg of ascorbic acid per milliliter. 
     
     
         46 . The composition of  claim 40 , wherein said radiopharmaceutical compound is 2-tert-butyl-4-chloro-5-[4-(2-[ 18 F]fluoro-ethoxymethyl)-benzyloxy]-2H-pyridazin-3-one: 
       
         
           
           
               
               
           
         
       
       wherein the composition comprises 50 mg of ascorbic acid per milliliter. 
     
     
         47 . The composition of  claim 46 , wherein the composition has a pH of 5.8. 
     
     
         48 . The composition of  claim 40 , wherein the composition comprises greater than 40 mg of ascorbic acid per milliliter, or greater than 50 mg of ascorbic acid per milliliter, or between 50 and 200 mg of ascorbic acid per milliliter. 
     
     
         49 . A method for preparing a composition of  claim 40 , comprising:
 adding a first solution comprising a radiopharmaceutical compound of formula:   
       
         
           
           
               
               
           
         
       
       wherein:
 X is O, S, or NR; 
 Y is O, S, NR, or CH 2 ; 
 R is H or Me; 
 m is 0, 1, 2, or 3; 
 n is 0, 1, 2, or 3; and 
 R 1  and R 2  are hydrogen or C 1-10 alkyl, 
 
       to a second solution comprising ascorbic acid within a pH range of 3.5 to less than 6, to form the radiopharmaceutical composition comprising the compound and ascorbic acid,
 wherein the radiopharmaceutical composition comprises greater than 20 mg of ascorbic acid per milliliter. 
 
     
     
         50 . The method of  claim 49 , wherein the composition comprises greater than 40 mg of ascorbic acid per milliliter, or greater than 50 mg of ascorbic acid per milliliter, or between 50 and 200 mg of ascorbic acid per milliliter, the method further comprising the step of adjusting the pH of the radiopharmaceutical composition to less than 6. 
     
     
         51 . The method of  claim 49 , wherein the radiopharmaceutical compound is
 (a) purified by chromatography, prior to addition of the first solution to the second solution, or   (b) not purified by chromatography, prior to addition of the first solution to the second solution.   
     
     
         52 . A method of myocardial imaging a patient, comprising:
 administering to the patient the composition of  claim 40 ; and   obtaining a myocardial image of the patient.