Compounds for Targeting Endothelial Cells, Compositions Containing the Same and Methods for Their Use

Abstract

The present invention provides compounds for targeting endothelial cells, tumor cells or other cells that express the NP-1 receptor, compositions containing the same and methods for their use. Additionally, the present invention includes diagnostic, therapeutic and radiotherapeutic compositions useful for visualization, therapy or radiotherapy.

1 . A composition for use in targeting endothelial cells, tumor cells or other cells which express NP-1, which comprises a compound of the formula (I)
   A-L-B  (I)
   in which   A is a monomer, multimer or polymer of TKPPR (SEQ ID NO:2), or a TKPPR (SEQ ID NO:2) analogue which contains TKPPR (SEQ ID NO:2) and which specifically binds to NP-1 or cells that express NP-1 with avidity that is equal to or greater than TKPPR (SEQ ID NO:2);   L is a linker; and   B is a substrate consisting essentially of a nanoparticle labeled with a fluorescent label.   
     
     
         2 . A composition according to  claim 1 , wherein B is a quantum dot. 
     
     
         3 . A process for preparing a compound of  claim 1  comprising:
 a) obtaining a monomer, multimer or polymer of TKPPR (SEQ ID NO:2) or an analogue thereof; 
 b) conjugating the monomer, multimer or polymer of TKPPR (SEQ ID NO:2) with the linker to give a compound of formula (IIb); and
   A-L  (IIb)
 
 
 c) forming a covalent or non-covalent bond between a compound of formula (IIb) and the substrate B or forming a covalent bond between the substrate B and the linker to form a conjugate B-L, and conjugating of the conjugate B-L with the monomer, multimer or polymer of TKPPR (SEQ ID NO:2) or an analogue thereof. 
 
     
     
         4 . A method of imaging an angiogenic site in a human or animal comprising:
 a) administering to said human or animal a composition according to  claim 1 ; and   b) detecting said nanoparticle small particle.   
     
     
         5 . A method of imaging endothelial cells, tumor cells or other cells that express NP-1 in a human or animal comprising:
 a) administering to said human or animal a composition comprising a compound according to  claim 1 ; and   b) detecting said nanoparticle small particle.   
     
     
         6 . A method of staging a tumor in a human or an animal comprising administering a composition comprising a compound of  claim 1  and an optional detectable moiety to said human or animal and detecting said moiety or said nanoparticle in said human or animal. 
     
     
         7 . A method of screening at least one agent for the ability of said agent to target endothelial cells, tumor cells or other cells that express NP-1, comprising contacting said cells in vitro with a composition of  claim 1  and an optional detectable moiety. 
     
     
         8 . A method for the therapeutic delivery in vivo of one or more nanoparticles to a patient suffering from effects associated with an angiogenesis-related disorder associated with NP-1 expression comprising administering a therapeutically effective amount of a composition of  claim 1 . 
     
     
         9 . A method of treating an individual exhibiting effects of an angiogenesis-related disorder associated with NP-1 expression comprising administering a therapeutically effective amount of a composition of  claim 1 , optionally further comprising a therapeutic moiety. 
     
     
         10 . A method for treating a human or animal with a tumor or angiogenesis-related disease associated with NP-1 expression comprising administering to said human or animal a therapeutically effective amount of a composition according to  claim 1 , optionally further comprising a therapeutic moiety. 
     
     
         11 - 37 . (canceled)