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

Abstract

The present invention generally relates to novel synthetic methods, systems, kits, salts, and precursors useful in medical imaging. In some embodiments, the present invention provides compositions comprising an imaging agent precursor, which may be formed using the synthetic methods described herein. An imaging agent may be converted to an imaging agent using the methods described herein. In some cases, the imaging agent is enriched in 18F. In some cases, an imaging agent including salt forms (e.g., ascorbate salt) 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.

1 - 102 . (canceled) 
     
     
         103 . A method of imaging a subject, comprising:
 administering a dose of a compound of the formula:   
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt, or combination thereof, to a subject, 
         wherein the maximum dose of the compound administered to the subject is approximately 15 mCi or less; and 
         acquiring at least one image of a portion of the subject. 
       
     
     
         104 . The method of  claim 103 , wherein the maximum dose of the compound or pharmaceutically acceptable salt thereof that is administered to the subject is approximately 13 mCi or less, is between approximately 10 mCi and approximately 13 mCi, or is between approximately 8 mCi and approximately 10 mCi. 
     
     
         105 . The method of  claim 103 , wherein the portion of the subject being imaged is at least a portion of the cardiovascular system, or at least a portion of a tumor, or is at least a portion of the heart. 
     
     
         106 . The method of  claim 103 , further comprising determining the presence or absence of a cardiovascular disease or condition in the subject. 
     
     
         107 . The method of  claim 103 , further comprising:
 administering a second dose of the compound or pharmaceutically acceptable salt thereof to the subject at a time subsequent to the dose of  claim 103 ; and   acquiring at least one image of the portion of the subject after the administration of the second dose.   
     
     
         108 . The method of  claim 107 , further comprising:
 comparing the at least one image acquired after the first dose with the at least one image acquired after the second dose; and   determining the presence or absence of differences between the cardiac sympathetic innervation at the time of administration of the first and second dose to the subject.   
     
     
         109 . The method of  claim 103 , wherein the compound is a pharmaceutically acceptable salt of formula (VI): 
       
         
           
           
               
               
           
         
       
       wherein X ⊖  is formate, wherein the fluorine is isotopically enriched with  18 F. 
     
     
         110 . The method of  claim 103 , wherein the compound is a pharmaceutically acceptable salt of formula (VII): 
       
         
           
           
               
               
           
         
       
       wherein X ⊖  is ascorbate, wherein the fluorine is isotopically enriched with  18 F. 
     
     
         111 . A method for detecting norepinephrine transporter (NET) in a portion of a subject, the method comprising:
 administering a dose of a compound of the formula:   
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, or combination thereof, to a subject, wherein the maximum dose of the compound administered to the subject is less than approximately 14 mCi; and
 acquiring at least one image of the portion of the subject, wherein the image detects NET in the subject, wherein the step of detecting comprises determining level, density, localization, and/or function of NET in the portion of the subject. 
 
     
     
         112 . The method of  claim 111 , wherein the maximum dose of the compound or pharmaceutically acceptable salt thereof that is administered to the subject is approximately 13 mCi or less, is between approximately 10 mCi and approximately 13 mCi, or is between approximately 8 mCi and approximately 10 mCi. 
     
     
         113 . The method of  claim 111 , wherein the portion of the subject being imaged is at least a portion of the cardiovascular system, or at least a portion of a tumor, or is at least a portion of the heart. 
     
     
         114 . The method of  claim 111 , further comprising determining the presence or absence of a cardiovascular disease or condition in the subject. 
     
     
         115 . The method of  claim 111 , further comprising:
 administering a second dose of the compound or pharmaceutically acceptable salt thereof to the subject at a time subsequent to the dose of  claim 103 ; and   acquiring at least one image of the portion of the subject after the administration of the second dose.   
     
     
         116 . The method of  claim 115 , further comprising:
 comparing the at least one image acquired after the first dose with the at least one image acquired after the second dose; and   determining the presence or absence of differences between the cardiac sympathetic innervation at the time of administration of the first and second dose.   
     
     
         117 . The method of  claim 111 , further comprising assessing cardiac sympathetic innervation in the subject. 
     
     
         118 . The method of  claim 111 , wherein image data from dynamic images are used to distinguish changes in local or global blood flow from changes in local or global NET function or distribution. 
     
     
         119 . The method of  claim 111 , further comprising providing image data using another imaging agent, and determining blood flow based on the image data to distinguish local or global blood flow from local or global changes in NET function or distribution. 
     
     
         120 . The method of  claim 111 , wherein the compound is a pharmaceutically acceptable salt of formula (VI): 
       
         
           
           
               
               
           
         
       
       wherein X ⊖  is formate, wherein the fluorine is isotopically enriched with  18 F. 
     
     
         121 . The method of  claim 111 , wherein the compound is a pharmaceutically acceptable salt of formula (VII): 
       
         
           
           
               
               
           
         
       
       wherein X ⊖  is ascorbate, wherein the fluorine is isotopically enriched with  18 F.