Compositions, methods, and systems for the synthesis and use of imaging agents

Abstract

The present invention relates to systems, compositions, and methods for the synthesis and use of imaging agents, or precursors thereof. An imaging agent precursor may be converted to an imaging agent using the methods described herein. In some cases, the imaging agent is enriched in 18 F. In some cases, an imaging agent may be used to image an area of interest in a subject, including, but not limited to, the heart, cardiovascular system, cardiac vessels, brain, and other organs. In some embodiments, methods and compositions for assessing perfusion and innervation mismatch in a portion of a subject are provided.

1 - 266 . (canceled) 
     
     
         267 . A compound of the formula: 
       
         
           
           
               
               
           
         
       
       wherein
 L is cyclic or acyclic alkylene; 
 R 1  is 
 
       
         
           
           
               
               
           
         
         R 2  is hydrogen; 
         R 3  is hydrogen, halogen, optionally substituted alkyl, or —OR A1 ; 
         R 4  is optionally substituted alkyl, or —OR A1 ; 
         R A1  is optionally substituted alkyl; 
         R 4  is substituted with an imaging moiety selected from the group consisting of  18 F,  76 Br,  124 I, and  131 I; or is associated with an imaging moiety selected from the group consisting of  64 Cu,  89 Zr,  99m Tc, and  111 In through a chelator; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         268 . (canceled) 
     
     
         269 . The compound of  claim 267  of the formula: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof. 
     
     
         270 . The compound of  claim 267  of the formula: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof. 
     
     
         271 - 274 . (canceled) 
     
     
         275 . A compound of the formula: 
       
         
           
           
               
               
           
         
       
       wherein
 L is substituted or unsubstituted, cyclic or acyclic alkylene; 
 R 1  is 
 
       
         
           
           
               
               
           
         
         R 2  is hydrogen, halogen, optionally substituted alkyl, or —OR A1 ; 
         R 3  is hydrogen, halogen, optionally substituted alkyl, or —OR A1 ; 
         R 4  is optionally substituted alkyl, —OR A1 ; 
         R 4  is substituted with an imaging moiety selected from the group consisting of  18 F,  76 Br,  124 I, and  131 I; or is associated with an imaging moiety selected from the group consisting of  64 Cu,  89 Zr,  99m Tc, and  111 In through a chelator; 
         R A1  is optionally substituted alkyl; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         276 . (canceled) 
     
     
         277 . The compound of  claim 275  of the formula: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof. 
     
     
         278 . The compound of  claim 275  of the formula: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof. 
     
     
         279 . The compound or pharmaceutically acceptable salt of  claim 275 , wherein R 2  is halogen. 
     
     
         280 - 373 . (canceled) 
     
     
         374 . The compound or pharmaceutically acceptable salt of  claim 267 , wherein R 4  is selected from: 
       
         
           
           
               
               
           
         
       
       wherein I m  is an imaging moiety selected from the group consisting of  18 F,  76 Br,  124 I, and  131 I. 
     
     
         375 . The compound or pharmaceutically acceptable salt of  claim 267 , wherein the I m  is  18 F. 
     
     
         376 . The compound of  claim 269  having the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         377 . A pharmaceutical composition comprising a compound of  claim 267 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 
     
     
         378 . A method of imaging a subject, comprising administering to the subject the pharmaceutical composition of  claim 377 , and obtaining an image of a portion of the subject. 
     
     
         379 . The method of  claim 378 , for imaging cardiac innervation or detecting norepinephrine transporter (NET). 
     
     
         380 . The compound or pharmaceutically acceptable salt of  claim 275 , wherein R 2  is hydrogen. 
     
     
         381 . The compound or pharmaceutically acceptable salt of  claim 275 , wherein R 4  is selected from: 
       
         
           
           
               
               
           
         
         wherein I m  is an imaging moiety selected from the group consisting of  18 F,  76 Br,  124 I, and  131 I. 
       
     
     
         382 . The compound or pharmaceutically acceptable salt of  claim 275 , wherein I m  is  18 F. 
     
     
         383 . The compound or pharmaceutically acceptable salt of  claim 275  having a structure selected from: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         384 . A pharmaceutical composition comprising a compound of  claim 275 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 
     
     
         385 . A method of imaging a subject, comprising administering to the subject the pharmaceutical composition of  claim 384 , and obtaining an image of a portion of the subject. 
     
     
         386 . The method of claim  285 , for imaging cardiac innervation or detecting norepinephrine transporter (NET).