Nir-conjugated tumor-specific antibodies and uses thereof

Abstract

Disclosed is a tumor-specific antibody and fluorophore conjugate for detecting, localizing and imaging of various tumors. Also disclosed are methods for detecting, localizing and imaging a solid tumor before or during a tumor resection surgery using the antibody-fluorophore conjugate.

What is claimed is: 
     
         1 . An antibody-fluorophore conjugate comprising a tumor-specific antibody conjugated to a near-infrared (NIR) fluorophore, wherein the antibody is a humanized antibody. 
     
     
         2 . The conjugate of  claim 1 , wherein the antibody is an anti-CEA antibody or an anti-TAG-72 antibody. 
     
     
         3 . The conjugate of  claim 2 , wherein the anti-CEA antibody is humanized anti-CEA T84.66-M5A antibody. 
     
     
         4 . The conjugate of  claim 1 , wherein the NIR fluorophore is Li-Cor IRDye800CW-NHS (IRDye800) or Intuitive IR800 free acid (Intuitive IR800). 
     
     
         5 . The conjugate of  claim 1 , wherein the antibody is further labeled with a radioactive isotope. 
     
     
         6 . The conjugate of  claim 5 , wherein the radioactive isotope is attached to the antibody via a chelating agent. 
     
     
         7 . The conjugate of  claim 6 , wherein the chelating agent is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). 
     
     
         8 . A method of detecting or localizing a solid tumor in a subject, comprising:
 a) administering to the subject an antibody-fluorophore conjugate comprising a tumor specific antibody conjugated to a near-infrared (NIR) fluorophore; and   b) scanning the subject with a scanning device at one or more time points after administration thereby to detect or localize the tumor.   
     
     
         9 . The method of  claim 8 , wherein the antibody is a humanized anti-CEA antibody or a humanized anti-TAG-72 antibody. 
     
     
         10 . The method of  claim 8 , wherein the antibody is humanized anti-CEA T84.66-M5A antibody. 
     
     
         11 . The method of  claim 8 , wherein the NIR fluorophore is Li-Cor IRDye800CW-NHS (IRDye800) or Intuitive IR800 free acid (Intuitive IR800). 
     
     
         12 . The method of  claim 8 , wherein the antibody-fluorophore conjugate is further labeled with a radioactive isotope via a chelating agent. 
     
     
         13 . The method of  claim 12 , wherein the chelating agent is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). 
     
     
         14 . The method of  claim 8 , wherein the subject suffers from colorectal cancer, pancreatic cancer, gastric cancer, lung cancer, breast cancer, ovarian cancer, or thyroid cancer. 
     
     
         15 . The method of  claim 8 , wherein the subject is scanned within 6 hours, within 8 hours, within 10 hours, within 12 hours, within 24 hours, within 36 hours, within 48 hours, within 72 hours, within 96 hours, or within 120 hours of administration of the conjugate. 
     
     
         16 . A method of tumor imaging to direct surgical resection of a solid tumor in a subject, comprising:
 a) administering to the subject an antibody-fluorophore conjugate comprising a tumor-specific antibody conjugated to a near-infrared (NIR) fluorophore; and   b) scanning the subject with a scanning device at one or more time points after administration thereby to guide resection of the tumor.   
     
     
         17 . The method of  claim 16 , wherein the antibody is a humanized anti-CEA antibody or a humanized anti-TAG-72 antibody. 
     
     
         18 . The method of  claim 16 , wherein the antibody is humanized anti-CEA T84.66-M5A antibody. 
     
     
         19 . The method of  claim 16 , wherein the antibody-fluorophore conjugate is further labeled with a radioactive isotope via a chelating agent. 
     
     
         20 . The method of  claim 16 , wherein the subject is scanned before surgery, during surgery, or both. 
     
     
         21 . The method of  claim 20 , wherein the subject is scanned before surgery to detect the radioactive label and during surgery to detect the fluorescent label. 
     
     
         22 . The method of  claim 16 , wherein the NIR fluorophore is Li-Cor IRDye800CW-NHS (IRDye800) or Intuitive IR800 free acid (Intuitive IR800). 
     
     
         23 . The method of  claim 16 , wherein the subject suffers from colorectal cancer, pancreatic cancer, gastric cancer, lung cancer, breast cancer, ovary cancer, or thyroid cancer.