Upar targeting peptide for use in peroperative optical imaging of invasive cancer

Abstract

There is provided a novel conjugate that binds to the cell surface receptor uPA (uPAR). The conjugate is based on a fluorescence-labeled peptide useful as a diagnostic probe to the surfaces of cells expressing uPAR. The conjugate is capable of carrying a suitable detectable and imageable label that will allow qualitative detection and also quantitation of uPAR levels in vitro and in vivo. This renders the surgical resection of tumors more optimal.

1 . A fluorophor labelled u PAR-targeting peptide conjugate having the formula:
   X-Y-(D-Asp)-([beta]-cyclohexyl-L-alanine)-(Phe)-(D-Ser)-(D-Arg)-(Tyr)-(Leu)-(Trp)-(Ser)   wherein,   X represents imageable moiety capable of detection either directly or indirectly in a optical imaging procedure, and   Y represents a spacer, a biomodifier or is absent   
     
     
         2 . A fluorophor labelled uPAR-targeting peptide conjugate as claimed in  claim 1  of the formula: 
       
         
           
           
               
               
           
         
         and pharmaceutically acceptable salts thereof. 
       
     
     
         3 . The compound of  claim 1  for use in fluorescence guided surgical resection of tumours. 
     
     
         4 . The compound of claim for use according to  claim 3 , wherein the compound is administered to a subject in a dose of 0.1-1000 mg per person. 
     
     
         5 . The compound of  claim 1  for peroperative optical imaging of cancer. 
     
     
         6 . A pharmaceutical composition for optical imaging of cancer, wherein the composition comprises a compound of  claim 1  together with at least one pharmaceutically acceptable carrier or excipient. 
     
     
         7 . The pharmaceutical composition of  claim 6 , wherein the concentration of the compound is 0.1-1000 mg per dosage unit. 
     
     
         8 . Use of a compound of  claim 1  for the manufacture of a diagnostic agent for use in a method of optical imaging of cancer involving administration of said compound to a subject and generation of an image of at least part of said subject. 
     
     
         9 . Use according to  claim 8 , wherein the compound is administered to the subject in a dose of 0.1-1000 mg per subject. 
     
     
         10 . A method of optical imaging of cancer of a subject involving administering a compound of  claim 1  to the subject and generating an optical image of at least a part of the subject to which said compound has distributed. 
     
     
         11 . Method of  claim 10 , wherein the compound of  claim 1  is administered to the subject in a dose of 0.1-1000 mg per subject.