3e8.scfv.cys-ir800 conjugate targeting tag-72 in an orthotopic colorectal cancer model

Abstract

Disclosed are compositions are anti-TAG-72 imaging agents and methods of their use.

What is claimed is: 
     
         1 . An anti-TAG-72 imaging agent comprising the formula Y-R, wherein Y comprises an anti-TAG-72 binding moiety and R comprises a first detectable label; wherein the first detectable label “R” comprises any dicyanine dye that emits fluorescent light that is detectable on a clinical optical NIRF imager at primarily above 800 nm. 
     
     
         2 . The anti-TAG-72 imaging agent of  claim 1 , wherein the dicyanin dye is selected from the group consisting of IRdye800, AlexaFluor 790, ZW-800, Indocyanine Green, and SO456. 
     
     
         3 . The anti-TAG-72 imaging agent of  claim 1 , wherein the anti-TAG-72 binding moiety comprises an antibody or TAG-72 binding antibody fragment. 
     
     
         4 . The anti-TAG-72 imaging agent of  claim 3 , wherein the anti-TAG-72 binding moiety comprises an antibody fragment comprising an scFv, F(ab′)2, or Fab′ that binds TAG-72. 
     
     
         5 . The anti-TAG-72 imaging agent of  claim 4 , wherein anti-TAG-72 binding moiety comprises 3E8.scFv. 
     
     
         6 . The anti-TAG-72 imaging agent of  claim 5 , wherein the 3E8.scFv comprises SEQ ID NO: 1. 
     
     
         7 . The anti-TAG-72 imaging agent of  claim 5 , wherein the 3E8.scFv has been modified to further comprise a terminal cysteine residue (3E8.scFv.Cys). 
     
     
         8 . The anti-TAG-72 imaging agent of  claim 7 , wherein the 3E8.scFv.Cys comprises SEQ ID No. 2. 
     
     
         9 . The anti-TAG-72 imaging agent of  claim 8 , wherein the dicyanin dye is selected from the group consisting of IRdye800, AlexaFluor 790, ZW-800, Indocyanine Green, and SO456. 
     
     
         10 . The anti-TAG-72 imaging agent of  claim 1 , wherein the binding molecule is used as an optical surgical navigation (OSN) agent administered intraparetoneally or intravenously. 
     
     
         11 . The anti-TAG-72 imaging agent of  claim 1 , further comprising a second detectable label. 
     
     
         12 . The anti-TAG-72 imaging agent of  claim 11 , wherein the second label is a radiolabel. 
     
     
         13 . An anti-TAG-72 imaging agent comprising the formula Y-R, wherein Y comprises an anti-TAG-72 binding moiety and “R” comprises a first detectable label; wherein the anti-TAG72 binding moiety “Y” comprises 3E8.scFv.Cys and wherein the first detectable label “R” comprises IRdye800. 
     
     
         14 . A method of performing surgical removal of a tumor in a subject comprising:
 a. administering to a subject the anti-TAG-72 imaging agent of  claim 1 ; and   b. guiding the surgical removal of the tumor using optical surgical navigation.   
     
     
         15 . The method of  claim 14 , wherein the method further comprises assaying the tumor using the anti-TAG-72 imaging agent to determine the possibility of surgical removal after step a and prior to step b. 
     
     
         16 . The method of  claim 14 , wherein the method further comprises monitoring the progress of the surgical removal. 
     
     
         17 . The method of  claim 14 , wherein the anti-TAG-imaging agent comprises a second detectable label and wherein the second label is a radiolabel. 
     
     
         18 . A method of making ®-anti-TAG-72 imaging agent comprising the formula Y-R, wherein Y comprises an anti-TAG-72 binding moiety and R comprises a first detectable label; wherein ® is a radioactive labeling atom that is useful for SPECT/CT or PET/CT, a radioactive labeling atom that is useful for RADS surgical guidance, or a radiolabeling atom useful for both SPECT/CT or PET/CT and RADS said method comprising
 a. providing an anti-TAG-72 imaging agent comprising a tyrosine residue; and 
 b. reacting the biomolecule with a chloramine and an iodine source under conditions effective to form an iodinated biomolecule, wherein the iodinated biomolecule comprises an iodinated tyrosine residue.