Imaging agents

Abstract

Provided herein is technology relating to imaging agents and particularly, but not exclusively, to methods of manufacturing fluorine-18-labeled phenethylguanidines and uses thereof.

1 - 205 . (canceled) 
     
     
         206 . A composition comprising an iodonium salt comprising a structure according to 
       
         
           
           
               
               
           
         
         or a salt, a free base, or a combination thereof, wherein: 
         a) R 1 , R 2 , R 3 , R 4 , and R 5  are independently selected from the group consisting of R 12 —I, hydrogen, halogen, hydroxyl, guanyl, alkoxy, haloalkoxy, alkyl, haloalkyl, amine, and an amine comprising a protecting group; 
         b) R 6  and R 7  are independently selected from the group consisting of hydrogen, hydroxyl, alkoxy, haloalkoxy, halogen, amino, alkyl, and haloalkyl; 
         c) R 8 , R 9 , R 10  and, R 11  are independently selected from the group consisting of hydrogen, carbamate, cyclic carbamate, amide, cyclic amide, and a nitrogen-protecting group; 
         d) and X −  is a counter ion. 
       
     
     
         207 . The composition of  claim 206  wherein R 12  is a phenyl ring or a heterocyclic ring comprising hydrogen, hydroxyl, alkyl, halogen, alkoxy, carbonyl, cyano, and/or a nitro group. 
     
     
         208 . The composition of  claim 206  wherein X −  is a counter ion selected from the group consisting of halide, sulfate, formate, borate, tosylate, trifluoracetate, triflate, mesylate, hexaflate, acetate, ascorbate, benzoate, and phosphate. 
     
     
         209 . A method of producing a  18 F-labeled phenethylguanidine comprising radiofluorinating an iodonium salt with an [ 18 F] fluoride ion source. 
     
     
         210 . The method of  claim 209  wherein the iodonium salt comprises a structure according to 
       
         
           
           
               
               
           
         
         or a salt, a free base, or a combination thereof, wherein: 
         a) R 1 , R 2 , R 3 , R 4 , and R 5  are independently selected from the group consisting of R 12 —I, hydrogen, halogen, hydroxyl, guanyl, alkoxy, haloalkoxy, alkyl, haloalkyl, amine, and an amine comprising a protecting group; 
         b) R 6  and R 7  are independently selected from the group consisting of hydrogen, hydroxyl, alkoxy, haloalkoxy, halogen, amino, alkyl, and haloalkyl; 
         c) R 8 , R 9 , R 10  and, R 11  are independently selected from the group consisting of hydrogen, carbamate, cyclic carbamate, amide, cyclic amide, and a nitrogen-protecting group; 
         d) and X −  is a counter ion. 
       
     
     
         211 . The method of  claim 209  wherein the [ 18 F] fluoride ion source is a no-carrier-added [ 18 F] fluoride ion source. 
     
     
         212 . The method of  claim 211  wherein the no-carrier-added [ 18 F] fluoride ion source is selected from the group consisting of potassium fluoride/Kryptofix[2,2,2], cesium fluoride, tetraalkylammonium fluoride, and a solid phase fluoride. 
     
     
         213 . The method of  claim 209  further comprising providing a free radical scavenger. 
     
     
         214 . The method of  claim 213  wherein the free radical scavenger is selected from the group consisting of 2,2,6,6-tetramethylpiperidine-N-oxide, 4-aminobenzoic acid, 1,1-diphenylethylene, galvinoxyl, gentisic acid, hydroquinone, thiophenol, DL-alpha-tocopherol, and 2,6-di-tert-butyl-4-methylphenol (BHT). 
     
     
         215 . The method of  claim 209  wherein radiofluorinating an iodonium salt with an [ 18 F] fluoride ion source occurs in an aqueous reaction. 
     
     
         216 . The method of  claim 209  further comprising heating or microwave irradiating a reaction vessel holding the iodonium salt and the [ 18 F] fluoride ion source. 
     
     
         217 . The method of  claim 209  further comprising deprotecting a group comprising a nitrogen. 
     
     
         218 . The method of  claim 209  further comprising purifying the  18 F-labeled phenethylguanidine by high-pressure liquid chromatography. 
     
     
         219 . A composition comprising a  18 F-labeled phenethylguanidine, wherein the  18 F-labeled phenethylguanidine is produced by a method comprising radiofluorinating an iodonium salt with an [ 18 F] fluoride ion source. 
     
     
         220 . The composition of  claim 219  wherein the iodonium salt comprises a structure according to 
       
         
           
           
               
               
           
         
         or a salt, a free base, or a combination thereof, wherein: 
         a) R 1 , R 2 , R 3 , R 4 , and R 5  are independently selected from the group consisting of R 12 —I, hydrogen, halogen, hydroxyl, guanyl, alkoxy, haloalkoxy, alkyl, haloalkyl, amine, and an amine comprising a protecting group; 
         b) R 6  and R 7  are independently selected from the group consisting of hydrogen, hydroxyl, alkoxy, haloalkoxy, halogen, amino, alkyl, and haloalkyl; 
         c) R 8 , R 9 , R 10  and, R 11  are independently selected from the group consisting of hydrogen, carbamate, cyclic carbamate, amide, cyclic amide, and a nitrogen-protecting group; 
         d) and X −  is a counter ion. 
       
     
     
         221 . The composition of  claim 219  wherein the [ 18 F] fluoride ion source is a no-carrier-added [ 18 F] fluoride ion source. 
     
     
         222 . The composition of  claim 221  wherein the no-carrier-added [ 18 F] fluoride ion source is selected from the group consisting of potassium fluoride/Kryptofix[2,2,2], cesium fluoride, tetraalkylammonium fluoride, and a solid phase fluoride. 
     
     
         223 . The composition of  claim 219  wherein the method further comprises providing a free radical scavenger. 
     
     
         224 . The composition of  claim 223  wherein the free radical scavenger is selected from the group consisting of 2,2,6,6-tetramethylpiperidine-N-oxide, 4-aminobenzoic acid, 1,1-diphenylethylene, galvinoxyl, gentisic acid, hydroquinone, thiophenol, DL-alpha-tocopherol, and 2,6-di-tert-butyl-4-methylphenol (BHT). 
     
     
         225 . The composition of  claim 219  wherein radiofluorinating an iodonium salt with an [ 18 F] fluoride ion source occurs in an aqueous reaction. 
     
     
         226 . The composition of  claim 219  wherein the method further comprises heating or microwave irradiating a reaction vessel holding the iodonium salt and the [ 18 F] fluoride ion source. 
     
     
         227 . The composition of  claim 219  wherein the method further comprises deprotecting a group comprising a nitrogen. 
     
     
         228 . The composition of  claim 219  wherein the method further comprises purifying the  18 F-labeled phenethylguanidine by high-pressure liquid chromatography.