Methods for Tumor Diagnosis and Therapy

Abstract

The present invention discloses a method for the enzyme-mediated, site-specific, in-vivo precipitation of a water soluble molecule in an animal. The enzyme is either unique to tumor cells, or is produced within a specific site (e.g., tumor) at concentrations that are higher than that in normal tissues. Alternatively, the enzyme is conjugated to a targeting moiety such as an antibody or a receptor-binding molecule.

1 .- 20 . (canceled) 
     
     
         21 . A method for the enzyme-mediated, site-specific, in-vivo localization of a water-insoluble molecule at a tumor site, comprising:
 administering to an animal a water-soluble prodrug having a structure:   
       
         
           
           
               
               
           
         
         or a biologically compatible salt form thereof, 
         wherein 
         R 1  is a radioactive atom or a radiolabeled moiety comprising one or more radioactive atoms, 
         R 2  is hydrogen, and 
         R 3  is a prosthetic group that is cleavable by an enzyme that is present at the tumor site, and 
         by virtue of said administering, the prodrug is hydrolyzed by the enzyme to form a water-insoluble drug at the tumor site. 
       
     
     
         22 . The method of  claim 21 , wherein the water-soluble prodrug has the structure: 
       
         
           
           
               
               
           
         
       
     
     
         23 . The method of  claim 22 , wherein R 1  is selected from the group consisting of a gamma emitting radionuclide, a positron emitting radionuclide, and an alpha or a beta particle emitting radionuclide. 
     
     
         24 . The method of  claim 22 , wherein R 1  is selected from the group consisting of astatine-211, bismuth-212, bismuth-213, bromine-77, iodine-123, iodine-124, iodine 125, iodine-131, copper-67, samarium-153, gold-198, palladium-109, rhenium-186, rhenium-188, dysprosium-165, strontium-89, phosphorous-32, phosphorous-33, and yttrium-90. 
     
     
         25 . The method of  claim 24 , wherein R 1  is radioactive iodine. 
     
     
         26 . The method of  claim 22 , wherein R 3  is selected from phosphate, sulfate, carbonate, and galactosyl. 
     
     
         27 . The method of  claim 26 , wherein R 3  is phosphate. 
     
     
         28 . The method of  claim 25 , wherein R 3  is phosphate. 
     
     
         29 . The method of  claim 22 , wherein said administering is by injection. 
     
     
         30 . The method of  claim 28 , wherein said injection is carried out intravenously, intra-arterially, subcutaneously, into the lymphatic circulation, intraperitoneally, intrathecally, intratumorally, or intravesically. 
     
     
         31 . The method of  claim 22 , wherein said animal is a human. 
     
     
         32 . A compound having a structure: 
       
         
           
           
               
               
           
         
         or a biologically compatible salt form thereof, 
         wherein 
         R 1  is a radioactive atom or a radiolabeled moiety comprising one or more radioactive atoms, 
         R 2  is hydrogen, and 
         R 3  is a prosthetic group that is hydrolytically cleavable by an enzyme. 
       
     
     
         33 . The compound of  claim 32 , having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         34 . The compound of  claim 33 , wherein R 1  is selected from the group consisting of a gamma emitting radionuclide, a positron emitting radionuclide, and an alpha or a beta particle emitting radionuclide. 
     
     
         35 . The compound of  claim 34 , wherein R 1  is selected from the group consisting of astatine-211, bismuth-212, bismuth-213, bromine-77, iodine-123, iodine-124, iodine 125, iodine-131, copper-67, samarium-153, gold-198, palladium-109, rhenium-186, rhenium-188, dysprosium-165, strontium-89, phosphorous-32, phosphorous-33, and yttrium-90. 
     
     
         36 . The compound of  claim 35 , wherein R 1  is radioactive iodine. 
     
     
         37 . The compound of  claim 33 , wherein R 3  is selected from phosphate, sulfate, carbonate, and galactosyl. 
     
     
         38 . The compound of  claim 37 , wherein R 3  is phosphate. 
     
     
         39 . The compound of  claim 36 , wherein R 3  is phosphate. 
     
     
         40 . The compound of  claim 32  comprised in a formulation suitable for injection. 
     
     
         41 . The compound of  claim 33  comprised in a formulation suitable for injection.