Molecular imaging contrast agents and uses thereof

Abstract

Compositions and methods for molecular imaging of selectins are disclosed. Specifically, compositions comprising medical imaging contrast-producing agents associated with the extracellular domain of TIM-1 as a targeting ligand for use in molecular imaging of selectins are disclosed. Also, methods of using the extracellular domain of TIM-1 as a ligand for achieving specific targeting to selectins as therapeutic drug delivery vehicles is also disclosed.

1 .- 33 . (canceled) 
     
     
         34 . A method of imaging a living subject comprising:
 a. administering to a subject a composition comprising a contrast-producing agent associated with a targeting ligand, wherein said targeting ligand comprises the amino acid sequence as set forth in SEQ ID NO: 2 or SEQ ID NO: 3 in a physiologically acceptable carrier;   b. allowing sufficient time for said composition to accumulate at a target site in the subject; and   c. imaging the subject using a diagnostic imaging modality.   
     
     
         35 . The method of  claim 34  wherein the diagnostic imaging modality is ultrasound. 
     
     
         36 . The method of  claim 34  wherein the time allowed for the composition to accumulate at the target site is between 1-60 minutes. 
     
     
         37 . The method of  claim 34 , wherein the sequence further comprises a fusion protein comprising a terminal cysteine. 
     
     
         38 . The method of  claim 34 , wherein the contrast-producing agent is an ultrasound contrast agent. 
     
     
         39 . The method of  claim 34 , wherein the sequence further comprises a fusion protein comprising human Fc. 
     
     
         40 . The method of  claim 34 , wherein the contrast-producing agent is an ultrasound contrast agent. 
     
     
         41 . The method of  claim 40 , wherein the ultrasound contrast-producing agent comprises gas-filled microbubbles and the targeting ligand is attached to said microbubbles by means of a covalent chemical bond. 
     
     
         42 . The method of  claim 34 , wherein the contrast-producing agent is an Mill contrast agent, a SPECT contrast agent, a PET contrast agent, or an optical imaging contrast agent. 
     
     
         43 . The method of  claim 34  wherein the target site of the living subject to be imaged is the heart. 
     
     
         44 . The method of  claim 34  wherein the target site of the living subject to be imaged is a tumor. 
     
     
         45 . The method of  claim 34  wherein said living subject is a mammal. 
     
     
         46 . The method of  claim 34  wherein said living subject is a human. 
     
     
         47 . The method of  claim 34  wherein said composition is administered to the living subject by intravenous, retro-orbital, subcutaneous, intraperitoneal, intra-lymphatic intravascular, oral, intramuscular, intraperitoneal, intralymphatic, subcutaneous, intranasal, intrarectal, interstitial, topically, or intratumoral injection, bolus or infusion. 
     
     
         48 . A method of delivering a therapeutically effective compound to a target site comprising:
 a. administering to the subject a composition comprising gas-filled microbubbles ultrasound contrast agent attached to a targeting ligand by means of a covalent chemical bond, wherein said targeting ligand comprises the amino acid sequence as set forth in SEQ ID NO: 2 or SEQ ID NO: 3, in combination with a therapeutic compound in a physiologically acceptable carrier,   b. allowing sufficient time for said composition to accumulate at the target site; and   c. applying acoustic energy to the subject in order to rupture the microbubbles thereby releasing said compound at the targeted site.