Imaging agents and methods of use thereof

Abstract

Compositions and methods useful in connection with magnetic resonance imaging are provided. Metabolites hyperpolarized by dynamic nuclear polarization are used as reporter molecules in nuclear magnetic resonance (“NMR”) spectroscopy to study metabolic pathways and diagnose disease states. The reporter molecules include hyperpolarized glutamine and hyperpolarized acetate. The invention includes the reporter molecules, compositions including the reporter molecules in pharmaceutically acceptable carriers, methods for studying metabolic pathways that include introducing one or more of the reporter molecules to a mammalian subject and imaging a target substance using NMR spectroscopy, and kits useful in studying metabolic pathways that incorporate one or more of the reporter molecules and instructions for their use.

1 . A method of studying a metabolic pathway in a subject, comprising:
 providing a quantity of a reporter molecule prepared from a precursor molecule hyperpolarized by dynamic nuclear polarization;   introducing the quantity of the reporter molecule to the subject; and   imaging a target substance by NMR spectroscopy, wherein the target substance is a constituent molecule of the metabolic pathway that incorporates the reporter molecule.   
     
     
         2 . The method of  claim 1 , wherein the subject is a mammal. 
     
     
         3 . The method of  claim 1 , wherein the metabolic pathway is the tricarboxylic acid pathway. 
     
     
         4 . The method of  claim 1 , wherein the reporter molecule is selected from the group consisting of hyperpolarized acetate and hyperpolarized glutamine. 
     
     
         5 . The method of  claim 1 , wherein the precursor molecule is selected from the group consisting of Formula I: 
       
         
           
           
               
               
           
         
       
       Formula II: 
       
         
           
           
               
               
           
         
       
       Formula III: 
       
         
           
           
               
               
           
         
       
     
     
         6 . A kit for studying a metabolic pathway in a subject, comprising:
 a reporter molecule prepared from a precursor molecule hyperpolarized by dynamic nuclear polarization; and   instructions for introducing a quantity of the reporter molecule to the subject and imaging a target substance by NMR spectroscopy, wherein the target substance is a constituent molecule of the metabolic pathway that incorporates the reporter molecule.   
     
     
         7 . The kit of  claim 6 , wherein the subject is a mammal. 
     
     
         8 . The kit of  claim 6 , wherein the metabolic pathway is the tricarboxylic acid pathway. 
     
     
         9 . The kit of  claim 6 , wherein the reporter molecule is selected from the group consisting of hyperpolarized acetate and hyperpolarized glutamine. 
     
     
         10 . The kit of  claim 6 , wherein the precursor molecule is selected from the group consisting of Formula I: 
       
         
           
           
               
               
           
         
       
       Formula II: 
       
         
           
           
               
               
           
         
       
       Formula III: 
       
         
           
           
               
               
           
         
       
     
     
         11 . A nuclear magnetic resonance imaging agent produced by the process comprising:
 providing a precursor molecule selected from the group consisting of an acetate molecule and a glutamine molecule; and   performing dynamic nuclear polarization on the precursor molecule such that the precursor molecule becomes hyperpolarized.   
     
     
         12 . The imaging agent of  claim 11 , wherein the T 1  of the imaging agent is between 40 and 60 seconds. 
     
     
         13 . The imaging agent of  claim 12 , wherein the hyperpolarization lasts for at least 5(T 1 ). 
     
     
         14 . The imaging agent of  claim 11 , wherein the hyperpolarized molecule is selected from the group consisting of: 
       Formula I: 
       
         
           
           
               
               
           
         
       
       Formula II: 
       
         
           
           
               
               
           
         
       
       Formula III: 
       
         
           
           
               
               
           
         
       
     
     
         15 . A pharmaceutical composition, comprising:
 A nuclear magnetic resonance imaging agent produced by the process comprising:
 providing a precursor molecule selected from the group consisting of an acetate molecule and a glutamine molecule; and 
 performing dynamic nuclear polarization on the precursor molecule such that the precursor molecule becomes hyperpolarized; and 
   a pharmaceutically acceptable carrier.   
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein the T 1  of the imaging agent is between 40 and 60 seconds. 
     
     
         17 . The pharmaceutical composition of  claim 16 , wherein the hyperpolarization lasts for at least 5(T 1 ). 
     
     
         18 . The pharmaceutical composition of  claim 15 , wherein the hyperpolarized molecule is selected from the group consisting of: 
       Formula I: 
       
         
           
           
               
               
           
         
       
       Formula II: 
       
         
           
           
               
               
           
         
       
       Formula III: