Compositions and Imaging Methods Comprising Detectably Labeled Phosphatidylethanolamine-Binding Peptides

Abstract

Disclosed are surprising discoveries concerning the role of anionic phospholipids and aminophospholipids in tumor vasculature and in viral entry and spread, and compositions and methods for utilizing these findings in the treatment of cancer and viral infections. Also disclosed are advantageous antibody, immunoconjugate and duramycin-based compositions and combinations that bind and inhibit anionic phospholipids and aminophospholipids, for use in the safe and effective treatment of cancer, viral infections and related diseases.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a substantially cell impermeant phosphatidylethanolamine (PE)-binding peptide that comprises a duramycin or cinnamycin peptide operatively attached to a cell impermeant group; wherein operative attachment of said duramycin or cinnamycin peptide to said cell impermeant group reduces the non-specific toxicity of the natural form of said duramycin or cinnamycin peptide by substantially inhibiting the ability of said duramycin or cinnamycin peptide to penetrate normal cells. 
     
     
         2 . A detectably labeled phosphatidylethanolamine (PE)-binding peptide, comprising a duramycin or cinnamycin peptide operatively attached to indium 111 , iodine 125 , iodine 131 , gadolinium, gallium 68  or technetium 99m . 
     
     
         3 . The detectably labeled PE-binding peptide of  claim 2 , comprising a duramycin or cinnamycin peptide operatively attached to technetium 99m . 
     
     
         4 . The detectably labeled PE-binding peptide of  claim 2 , comprising a cinnamycin peptide operatively attached to technetium 99m . 
     
     
         5 . The detectably labeled PE-binding peptide of  claim 2 , comprising a duramycin peptide operatively attached to technetium 99m . 
     
     
         6 . The detectably labeled PE-binding peptide of  claim 2 , wherein said detectably labeled PE-binding peptide is formulated in a unit dosage formulation or as an injectable formulation. 
     
     
         7 . A method for forming an image of a disease site in an animal having a disease connected with the presence of the aminophospholipid, phosphatidylethanolamine (PE), at the cell surface, said method comprising administering to said animal a diagnostically effective amount of a detectably labeled PE-binding peptide that comprises a duramycin or cinnamycin peptide operatively attached to a detectable marker that is detectable by a non-invasive method; allowing sufficient time for said detectably labeled PE-binding peptide to localize and bind to cells expressing phosphatidylethanolamine in said disease site; and exposing said animal to a detection device to identify said detectable marker, thus forming an image of said disease site. 
     
     
         8 . The method of  claim 7 , wherein said detectably labeled PE-binding peptide comprises a cinnamycin peptide operatively attached to said detectable marker. 
     
     
         9 . The method of  claim 7 , wherein said detectably labeled PE-binding peptide comprises a duramycin peptide operatively attached to said detectable marker. 
     
     
         10 . The method of  claim 7 , wherein said detectably labeled PE-binding peptide comprises a duramycin or cinnamycin peptide operatively attached to a detectable marker that is detectable using a nuclear magnetic imaging device. 
     
     
         11 . The method of  claim 7 , wherein said detectably labeled PE-binding peptide comprises a duramycin or cinnamycin peptide operatively attached to a detectable marker that is detectable using a gamma scintillation camera or detector. 
     
     
         12 . The method of  claim 11 , wherein said detectably labeled PE-binding peptide comprises a duramycin or cinnamycin peptide operatively attached to technetium 99m . 
     
     
         13 . The method of  claim 11 , wherein said detectably labeled PE-binding peptide comprises a duramycin peptide operatively attached to technetium 99m . 
     
     
         14 . The method of  claim 7 , wherein said cells expressing phosphatidylethanolamine in said disease site are apoptotic cells. 
     
     
         15 . The method of  claim 7 , wherein said disease connected with the presence of phosphatidylethanolamine at the cell surface is cancer. 
     
     
         16 . The method of  claim 15 , wherein said cells expressing phosphatidylethanolamine in said disease site are tumor cells. 
     
     
         17 . The method of  claim 15 , wherein said cells expressing phosphatidylethanolamine in said disease site are cells of the tumor vasculature. 
     
     
         18 . The method of  claim 7 , wherein said disease connected with the presence of phosphatidylethanolamine at the cell surface is a viral infection disease. 
     
     
         19 . The method of  claim 7 , wherein said disease connected with the presence of phosphatidylethanolamine at the cell surface is vascular thromboses, pulmonary embolism, myocardial infarction or stroke. 
     
     
         20 . The method of  claim 7 , wherein said disease connected with the presence of phosphatidylethanolamine at the cell surface is atherosclerosis. 
     
     
         21 . The method of  claim 7 , wherein said detectably labeled peptide is formulated as a one time dosage for imaging.