Pet-imaging immunomodulators

Abstract

The invention relates to the synthesis and use of 18 F-labeled millamolecules for imaging various processes within the body, for detecting the location of molecules associated with disease pathology, and for monitoring disease progression are disclosed.

What is claimed is: 
     
         1 . A compound of formula (I) 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein x is an integer from 1 to 8 and R is a C 1 -C 6 alkyl group. 
     
     
         2 . A compound of  claim 1  of formula (II) 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein x is an integer from 1 to 8 and R is C 1 -C 6 alkyl group. 
     
     
         3 . A compound of  claim 1  of formula (III) 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         4 . A compound of formula (IV) 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein x is an integer from 1 to 8 and R is C 1 -C 6 alkyl group. 
     
     
         5 . A compound of  claim 4  of formula (V) 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         6 . A method of obtaining an image of a compound of  claim 1 , the method comprising,
 a) administering the compound to a subject; and   b) imaging in vivo the distribution of the compound positron emission tomography (PET) scanning.   
     
     
         7 . The method of  claim 6 , wherein the imaged distribution of the compound of  claim 1  is indicative of the presence or absence of a disease. 
     
     
         8 . A method of monitoring the progress of a disease in a subject, the method comprising
 (a) administering to a subject in need thereof a compound of  claim 1  which binds to a target molecule associated with the presence of the disease at a first time point and obtaining an image of at least a portion of the subject to determine the amount of the diseased cells or tissue; and   (b) administering to the subject compound of  claim 1  at one or more subsequent time points and obtaining an image of at least a portion of the subject at each time point; wherein the dimension and location of the diseased cells or tissue at each time point is indicative of the progress of the disease.   
     
     
         9 . A method of quantifying diseased cells or tissues in a subject, the method comprising
 (a) administering to a subject having diseased cells or tissues a compound of  claim 1  which binds to a target molecule located with the diseased cells or tissues; and   (b) detecting radioactive emissions of the  18 F in the diseased cells or tissue, wherein the level and distribution of the radioactive emissions in the diseased cells or tissues is a quantitative measure of the diseased cells or tissues.   
     
     
         10 . The method of  claim 9  wherein the disease is selected from the group consisting of solid cancers, hematopoietic cancers, hematological cancers, autoimmune disease, neurodegenerative disease cardiovascular disease, and pathogenic infection. 
     
     
         11 . A method of obtaining a quantitative image of tissues or cells expressing PD-L1, the method comprising contacting the cells or tissue with a compound of  claim 1  which binds to PD-L1, and detecting or quantifying the tissue expressing PD-L1 using positron emission tomography (PET). 
     
     
         12 . A method of screening for an agent for treating a disease comprising the steps of
 (a) contacting cells expressing PD-L1 with a compound of  claim 1  which binds to PD-L1 in the presence and absence of a candidate agent; and   (b) imaging the cells in the presence and absence of the candidate agent using positron emission tomography (PET),   
       wherein a decrease in the amount of radioactive emissions in the presence of the candidate agent is indicative of that the agent binds to PD-L1. 
     
     
         13 . A pharmaceutical composition comprising a compound of  claim 1 . 
     
     
         14 . A kit comprising the reaction precursors for use in producing the compound of claiml, and instructions for producing the compound of  claim 1 .