Compositions and Methods for Imaging

Abstract

The present disclosure provides compositions for in vivo imaging of hydrogen peroxide; and methods for detecting hydrogen peroxide in vivo. The compositions and methods find use in various diagnostic applications, which are also provided.

What is claimed is: 
     
         1 . A compound of the formula: 
       
         
           
           
               
               
           
         
         wherein Z is a aryl or a heteroaryl group, that includes one or more isotopically labeled atoms capable of being hyperpolarized by dynamic nuclear polarization. 
       
     
     
         2 . The compound of  claim 1 , wherein Z is a pyridyl group that may be unsubstituted or substituted with one or more R 1  groups, wherein each R 1  is independently selected from hydrogen, deuterium, a halogen, cyano, nitro, a trihalomethyl, an alkoxy, an aryloxy, an alkyl, an aryl, a heterocycle, a thiol, a thioether, an acyl, and hydroxyl. 
     
     
         3 . The compound of  claim 1 , Z is a phenyl group that is unsubstituted or substituted with one or more R 1  groups. 
     
     
         4 . The compound of  claim 3 , wherein the compound is of the formula: 
       
         
           
           
               
               
           
         
         wherein R 1  is one or more groups, each R 1  independently selected from hydrogen, deuterium, a halogen, cyano, nitro, a trihalomethyl, an alkoxy, an aryloxy, an alkyl, an aryl, a heterocycle, a thiol, a thioether, an acyl, and hydroxyl, 
         wherein at least one atom is labeled with an isotope suitable for hyperpolarization. 
       
     
     
         5 . The compound of  claim 4 , wherein the compound comprises at least one  13 C atom as shown in one of the following structures: 
       
         
           
           
               
               
           
         
         wherein R 2  is one or more groups, each R 2  independently selected from hydrogen, deuterium, a halogen, cyano, nitro, a trihalomethyl, an alkoxy, an aryloxy, an alkyl, an aryl, a heterocycle, a thiol, a thioether, an acyl, and hydroxyl. 
       
     
     
         6 . The compound of  claim 4 , wherein the compound is of the formula: 
       
         
           
           
               
               
           
         
         wherein R 11 , R 12 , R 13 , R 14  and R 15  are each independently selected from hydrogen, deuterium, a halogen, cyano, nitro, a trihalomethyl, an alkoxy, an aryloxy, an alkyl, an aryl, a heterocycle, a thiol, a thioether, an acyl, and hydroxyl. 
       
     
     
         7 . The compound of  claim 4 , wherein the compound is of one of the following formulas: 
       
         
           
           
               
               
           
         
         wherein R 21 , R 22 , R 23 , R 31 , R 32  and R 33  are each independently selected from hydrogen, deuterium, a halogen, cyano, nitro, a trihalomethyl, an alkoxy, an aryloxy, an alkyl, an aryl, a heterocycle, a thiol, a thioether, an acyl, and hydroxyl 
       
     
     
         8 . The compound of  claim 4 , wherein the compound is of one of the following structures: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         9 . The compound of  claim 2 , wherein the compound is a compound of one of the following formulas: 
       
         
           
           
               
               
           
         
         wherein R 1  is one or more groups, each R 1  independently selected from hydrogen, deuterium, a halogen, cyano, nitro, a trihalomethyl, an alkoxy, an aryloxy, an alkyl, an aryl, a heterocycle, a thiol, a thioether, an acyl, and hydroxyl; and 
         wherein at least one atom is labeled with an isotope suitable for hyperpolarization by DNP. 
       
     
     
         10 . The compound of  claim 1 , wherein the at least one isotopically labeled atom is selected from  13 C and  15 N. 
     
     
         11 . A composition comprising:
 a) a compound of  claim 1 ; and   b) a buffer.   
     
     
         12 . A pharmaceutical composition comprising:
 a) a compound of  claim 1 ; and   b) a pharmaceutically acceptable excipient.   
     
     
         13 . A method of detecting hydrogen peroxide in a cell, tissue, or organ, or extracellularly in an individual, the method comprising:
 a) administering to the individual a compound of  claim 1 , or a composition of  claim 11  or  claim 12 ; and   b) detecting a signal produced by the compound upon reaction with hydrogen peroxide.   
     
     
         14 . The method of  claim 13 , wherein the compound is hyperpolarized, and wherein said detecting is by hyperpolarized magnetic resonance imaging. 
     
     
         15 . The method of  claim 13 , wherein hydrogen peroxide is selectively detected in a range of from about 2.5 μM to about 250 μM. 
     
     
         16 . The method of  claim 13 , wherein the individual is a human. 
     
     
         17 . The method of  claim 13 , wherein said detecting is performed at a first time and at a second time that is later than the first time. 
     
     
         18 . The method of  claim 17 , wherein the first time is before administration of a therapeutic agent to the individual, and the second time is after administration of a therapeutic agent to the individual. 
     
     
         19 . The method of  claim 13 , wherein said detecting provides for diagnosis of a disease or disorder characterized at least in part by an excess of hydrogen peroxide. 
     
     
         20 . The method of  claim 13 , wherein said detecting provides for a determination of the efficacy of a therapeutic agent or other treatment for a disease or disorder characterized at least in part by an excess of hydrogen peroxide. 
     
     
         21 . The method of  claim 20 , wherein the disease or disorder characterized at least in part by an excess of hydrogen peroxide is cancer, inflammation, aging, cardiovascular disease, diabetes, neurodegenerative disease, or stroke.