Methods for cancer imaging

Abstract

Methods are provided for cancer and pre-cancer detection by increased uptake of fluorophore glucose or deoxyglucose conjugates in cancerous and pre-cancerous cells relative to normal cells.

1 . A method for detecting or imaging cancer in a subject, said method comprising: 
 (a) administering to said subject an effective amount of a fluorophore glucose, deoxyglucose or derivative conjugate; and    (b) detecting or imaging cells that take up said fluorophore conjugate to determine if cancer is present in said subject.    
     
     
         2 . A method in accordance with  claim 1 , wherein said fluorophore conjugate has the formula:  
         Fl-L-Glc  
       wherein 
 Fl is a fluorophore;  
 L is a bond or a linking group; and  
 Glc is glucose, deoxyglucose or a glucose or deoxyglucose derivative.  
 
     
     
         3 . A method in accordance with  claim 2 , wherein said Glc is deoxyglucose or a deoxyglucose derivative selected from the group consisting of D-(+)-deoxyglucose, D-(+)-glucosamine and N-acetyl D-glucosamine, and said Fl is a fluorophore having an emission wavelength of from about 400 nm to about 1200 nm.  
     
     
         4 . A method in accordance with  claim 2 , wherein Fl is a fluorophore selected from the group consisting of nitrobenzoxazole dyes, cyanine dyes, dipyrrometheneboron dyes, coumarin dyes, benzocoumarin dyes, xanthene dyes, benzo[a]xanthene dyes, benzo[b]xanthene dyes, benzo[c]xanthene dyes, phenoxazine dyes, benzo[a]phenoxazine dyes, benzo[b]phenoxazine dyes and benzo[c]phenoxazine dyes.  
     
     
         5 . A method in accordance with  claim 2 , wherein L is a linking group having from 2 to 30 chain atoms selected from the group consisting of C, N, O, P, S and Si.  
     
     
         6 . A method in accordance with  claim 2 , wherein said fluorophore glucose or deoxyglucose conjugate has a formula selected from the group consisting of:  
       
         
           
           
               
               
           
         
       
       wherein 
 Fl is a fluorophore;  
 L is a linking group;  
 each X is independently selected from the group consisting of O and NH;  
 R 1 , R 3  and R 4  are each members independently selected from the group consisting of H, (C 1 -C 12 )alkyl, (C 1 -C 12 )acyl and a solubility or partitioning effector component.  
 
     
     
         7 . A method in accordance with  claim 1 , wherein said detecting or imaging is carried out in combination with a cancer resection.  
     
     
         8 . A method in accordance with  claim 1 , wherein said cancer cells are selected from the group consisting of lung cancer cells, breast cancer cells, prostate cancer cells, colon cancer cells, cervical cancer cells, esophageal cancer cells, bladder cancer cells, head and neck cancer cells and melanoma cells.  
     
     
         9 . A method in accordance with  claim 1 , further comprising a preliminary step of reducing glucose ingestion in said subject.  
     
     
         10 . A method of detecting pre-cancerous cells in a subject, said method comprising: 
 (a) administering to said subject an effective amount of a fluorophore glucose or deoxyglucose conjugate; and    (b) detecting or imaging pre-cancer cells that take up said fluorophore conjugate to determine if pre-cancer cells are present in said subject.    
     
     
         11 . A method in accordance with  claim 10 , wherein said fluorophore conjugate has the formula:  
         Fl-L-Glc  
       wherein 
 Fl is a fluorophore;  
 L is a bond or a linking group; and  
 Glc is glucose, deoxyglucose or a glucose or deoxyglucose derivative.  
 
     
     
         12 . A method in accordance with  claim 11 , wherein Fl is a fluorophore selected from the group consisting of nitrobenzoxazole dyes, cyanine dyes, dipyrrometheneboron dyes, coumarin dyes, benzocoumarin dyes, xanthene dyes, benzo[a]xanthene dyes, benzo[b]xanthene dyes, benzo[c]xanthene dyes, phenoxazine dyes, benzo[a]phenoxazine dyes, benzo[b]phenoxazine dyes and benzo[c]phenoxazine dyes  
     
     
         13 . A method in accordance with  claim 10 , wherein said administering is intravenous, oral or topical.  
     
     
         14 . A method in accordance with  claim 13 , wherein said pre-cancerous cells are associated with Barrett Esophagus, colonic polyps and inflammatory bowel disease.  
     
     
         15 . A fluorophore conjugate having the formula:  
         Fl-L-Glc  
       wherein 
 Fl is a fluorophore having an emission wavelength of from about 400 nm to about 1200 nm;  
 L is a bond or a linking group; and  
 Glc is glucose, deoxyglucose or a glucose or deoxyglucose derivative, with the proviso that said fluorophore deoxyglucose conjugate is other than 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose.  
 
     
     
         16 . A fluorophore conjugate of  claim 15 , having a formula selected from the group consisting of:  
       
         
           
           
               
               
           
         
       
       wherein 
 Fl is a fluorophore;  
 L is a linking group;  
 each X is independently selected from the group consisting of O and NH;  
 R 1 , R 3  and R 4  are each members independently selected from the group consisting of H, (C 1 -C 12 )alkyl, (C 1 -C 12 )acyl and a solubility or partitioning effector component.  
 
     
     
         17 . A fluorophore conjugate of  claim 16 , wherein Fl is selected from the group consisting of coumarins, xanthenes, phenoxazines and cyanines.  
     
     
         18 . A method for cancer or pre-cancer detection during an operative or endoscopic procedure, said method comprising: 
 (a) administering to a patient subject to said procedure, an effective amount of a fluorescent glucose or deoxyglucose conjugate, said conjugate having a rate of uptake in cancerous or pre-cancerous cells that is at least two times greater than the rate of uptake in normal cells;    (b) conducting said procedure within 48 hours of said administering;    (c) scanning said patient with a detection means for detecting the localization of said fluorescent conjugate in said cancer or pre-cancer cells.    
     
     
         19 . A method in accordance with  claim 18 , wherein said procedure is conducted within 24 hours of said administering and is either an operative procedure or an endoscopic procedure, and wherein said method further comprises treating sites of conjugate accretion by external beam radiation, laser therapy, or surgical removal.  
     
     
         20 . A kit comprising a vial containing a sterile preparation for human use of a fluorophore glucose, deoxyglucose or derivative conjugate and a pharmaceutically acceptable carrier.