Novel epithelial tissue imaging agent

Abstract

Targeting molecules are provided for use in delivering imaging agents to epithelial tissue. The targeting molecule comprises a polypeptide that forms a closed covalent loop, contains at least three peptide domains having β-sheet character, each of the domains being separated by domains lacking β-sheet character. The targeting molecule specifically binds to a basolateral factor attached to a basolateral domain of an epithelial cell surface causing internalization of a linked imaging agent into the cells. The polypeptide or imaging agent may be linked to a peptide amino acid sequence that directs delivery of the imaging agent to a carcinoma cell, a nucleus, or an endoplasmic reticulum.

1 . A targeting molecule capable of specifically binding to a basolateral factor associated with an epithelial surface and causing the internalization of an imaging agent linked thereto, wherein the targeting molecule is not full length dimeric IgA.  
     
     
         2 . A targeting molecule linked to at least one imaging agent, wherein said targeting molecule comprises a polypeptide that: 
 (a) forms a closed covalent loop; and    (b) contains at least three peptide domains having β-sheet character, each of the domains being separated by domains lacking β-sheet character;    wherein said targeting molecule is linked to at least one imaging agent by a substrate for an intracellular or extracellular enzyme associated with an epithelial barrier.    
     
     
         3 . A targeting molecule according to  claim 2 , wherein said enzyme is selected from the group consisting of proteases, glycosidases, phospholipases, esterases, hydrolases and nucleases.  
     
     
         4 . A targeting molecule linked to at least one imaging agent, wherein said targeting molecule comprises a polypeptide that: 
 (a) forms a closed covalent loop; and    (b) contains at least three peptide domains having β-sheet character, each of the domains being separated by domains lacking β-sheet character;    wherein said targeting molecule is linked to at least one imaging agent through a side chain of amino acids in an antibody combining site.    
     
     
         5 . A targeting molecule linked to at least one imaging agent, wherein said targeting molecule comprises a polypeptide that: 
 (a) forms a closed covalent loop; and    (b) contains at least three peptide domains having β-sheet character, each of the domains being separated by domains lacking β-sheet character;    wherein the imaging agent is not naturally associated with the targeting molecule, and wherein the imaging agent is not iodine.    
     
     
         6 . A targeting molecule according to  claim 5 , wherein said imaging agent is selected from the group consisting of metals, radioactive isotopes, radioopaque agents, radiolucent agents, contrast agents, dyes and enzymes.