ST receptor binding compounds and methods of using the same

Abstract

Conjugated compounds which comprises an ST receptor binding moiety and a radiostable active moiety are disclosed. Pharmaceutical compositions comprising a pharmaceutically acceptable carrier or diluent, and a conjugated compound which comprises an ST receptor binding moiety and a radiostable active moiety or an ST receptor binding moiety and a radioactive active moiety are disclosed. Methods of treating an individual suspected of suffering from metastasized colorectal cancer comprising the steps of administering to said individual a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent, and a therapeutically effective amount of a conjugated compound which comprises an ST receptor binding moiety and a radiostable active moiety or an ST receptor binding moiety and a radiostable active moiety are disclosed. Methods of radioimaging metastasized colorectal cancer cells comprising the steps of first administering to an individual suspected of having metastasized colorectal cancer cells, a pharmaceutical composition that comprises a pharmaceutically acceptable carrier or diluent, and conjugated compound that comprises an ST receptor binding moiety and a radioactive active moiety wherein the conjugated compound is present in an amount effective for diagnostic use in humans suffering from colorectal cancer and then detecting the localization and accumulation of radioactivity in the individual's body are disclosed.

1 . A conjugated compound comprising: 
 a) a ST receptor binding moiety; and    b) an active moiety;    wherein said active moiety is a radiostable active agent.    
     
     
         2 . The compound of  claim 1  wherein said ST receptor binding moiety is a peptide.  
     
     
         3 . The compound of  claim 1  wherein said ST receptor binding moiety is selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:3, SEQ ID NOS:5-54 and fragments and derivatives thereof.  
     
     
         4 . The compound of  claim 1  wherein said ST receptor binding moiety is selected from the group consisting of SEQ ID:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6 and SEQ ID NO:54.  
     
     
         5 . The compound of  claim 1  wherein said active moiety is a therapeutic agent.  
     
     
         6 . The compound of  claim 1  wherein said active moiety is selected from the group consisting of: methotrexate, doxorubicin, daunorubicin, cytosinarabinoside, etoposide, 5-4 fluorouracil, melphalan, chlorambucil, cis-platin, vindesine, mitomycin, bleomycin, purothionin, macromomycin, 1,4-benzoquinone derivatives, trenimon, ricin, ricin A chain,  Pseudomonas  exotoxin, diphtheria toxin,  Clostridium perfringens  phospholipases C, bovine pancreatic ribonuclease, pokeweek antiviral protein, abrin, abrin A chain, cobra venom factor, gelonin, saporin, modeccin, viscumin, volkensin, alkaline phosphatase, nitroimidazole, metronidazole and misonidazole.  
     
     
         7 . The compound of  claim 1  wherein: 
 a) said ST receptor binding moiety is selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:3, SEQ ID NOS:5-54 and fragments and derivatives thereof;    b) said an active moiety is selected from the group consisting of: methotrexate, doxorubicin, daunorubicin, cytosinarabinoside, etoposide, 5-4 fluorouracil, melphalan, chlorambucil, cis-platin, vindesine, mitomycin, bleomycin, purothionin, macromomycin, 1,4-benzoquinone derivatives, trenimon, ricin, ricin A chain,  Pseudomonas  exotoxin, diphtheria toxin,  Clostridium perfringens  phospholipases C, bovine pancreatic ribonuclease, pokeweed antiviral protein, abrin, abrin A chain, cobra venom factor, gelonin, saporin, modeccin, viscumin, volkensin, alkaline phosphatase, nitroimidazole, metronidazole and misonidazole.    
     
     
         8 . The compound of  claim 1  wherein said an active moiety is selected from the group consisting of: methotrexate, doxorubicin, daunorubicin, cytosinarabinoside, cis-platin, vindesine, mitomycin and bleomycin, alkaline phosphatase, ricin A chain,  Pseudomonas  exotoxin and diphtheria toxin.  
     
     
         9 . The compound of  claim 1  wherein: 
 a) said ST receptor binding moiety is selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6 and SEQ ID NO:54; and    b) said an active moiety is selected from the group consisting of: methotrexate, doxorubicin, daunorubicin, cytosinarabinoside, cis-platin, vindesine, mitomycin and bleomycin, alkaline phosphatase, ricin A chain,  Pseudomonas  exotoxin and diphtheria toxin.    
     
     
         10 . A pharmaceutical composition comprising: 
 a) a pharmaceutically acceptable carrier or diluent, and    b) a conjugate compound according to  claim 1 .    
     
     
         11 . A method of treating an individual suspected of suffering from metastasized colorectal cancer comprising the steps of administering to said individual a pharmaceutical composition according to  claim 10 .  
     
     
         12 . A pharmaceutical composition comprising: 
 a) a pharmaceutically acceptable carrier or diluent, and,    b) conjugated compound comprising: 
 i) a ST receptor binding moiety; and  
 ii) an active moiety wherein said active moiety is a radioactive agent and said conjugated compound is present in an amount effective for therapeutic or diagnostic use in humans suffering from colorectal cancer.  
   
     
     
         13 . The pharmaceutical composition of  claim 12  wherein said active moiety is selected from the group consisting of:  47 Sc,  67 Cu,  90 Y,  109 Pd,  123 I,  125 I,  131 I,  186 Re,  199 Au,  211 At,  212 Pb,  212 B,  32 P,  33 P,  77 Ge,  77 As,  103 Pb,  105 Rh,  111 Ag,  119 Sb,  121 Sn,  131 Cs,  143 Pr,  161 Tb,  177 Lu,  191 Os,  193M Pt and  197 Hg.  
     
     
         14 . The pharmaceutical composition of  claim 12  wherein said active moiety is selected from the group consisting of:  43 K,  52 Fe,  57 Co,  67 Cu,  67 Ga,  68 Ga,  77 Br,  81 Rb/ 81M Kr,  87M Sr,  99M Tc,  111 In,  113 In,  123 I,  125 I,  127 Cs,  129 Cs,  131 I,  132 I,  197 Hg,  203 Pb and  206 Bi.  
     
     
         15 . The pharmaceutical composition of  claim 12  wherein said ST receptor binding moiety is a peptide.  
     
     
         16 . The pharmaceutical composition of  claim 12  wherein said ST receptor binding moiety is selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:3, SEQ ID NOS:5-54 and fragments and derivatives thereof.  
     
     
         17 . The pharmaceutical composition of  claim 12  wherein said ST receptor binding moiety is selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6 and SEQ ID NO:54.  
     
     
         18 . The pharmaceutical composition of  claim 12  wherein said ST receptor binding moiety is selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6 and SEQ ID NO:54, and said active moiety is selected from the group consisting of:  47 Sc,  67 Cu,  90 Y,  109 Pd,  123 I,  125 I,  131 I,  186 Re,  188 Re,  199 Au,  211 At,  212 Pb,  212 B,  32 P and  33 P,  71 Ge,  77 As,  103 Pb,  105 Rh,  111 Ag,  119 Sb,  121 Sn,  131 Cs,  143 Pr,  161 Tb,  177 Lu,  191 Os,  193M Pt and  197 Hg.  
     
     
         19 . The pharmaceutical composition of  claim 12  wherein said ST receptor binding moiety is selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO.5, SEQ ID NO:6 and SEQ ID NO:54, and said active moiety is selected from the group consisting of  43 K,  53 Fe,  57 Co,  67 Cu,  67 Ga,  68 Ga,  77 Br,  81 Rb/ 81M Kr,  87M Sr,  99M Tc,  111 In,  123 I,  125 I,  127 Cs,  129 Cs,  131 I,  132 I,  197 Hg,  203 Pb and  206 Bi.  
     
     
         20 . A method of radioimaging metastasized colorectal cancer cells comprising the steps of administering to an individual a pharmaceutical composition comprising: 
 a) a pharmaceutically acceptable carrier or diluent, and    b) conjugated compound comprising: 
 i) a ST receptor binding moiety; and  
 ii) an active moiety;  
 wherein said active moiety is a radioactive agent and said conjugated compound is present in an amount effective for diagnostic use in humans suffering from colorectal cancer.  
   
     
     
         21 . A method of treating an individual suspected of suffering from metastasized colorectal cancer comprising the steps of administering to said individual a pharmaceutical composition comprising: 
 a) a pharmaceutically acceptable carrier or diluent, and,    b) conjugated compound comprising: 
 i) a ST receptor binding moiety; and  
 ii) an active moiety;  
 wherein said active moiety is a radiostable agent or radioactive agent and said conjugated compound is present in an amount effective for therapeutic or diagnostic use in humans suffering from colorectal cancer.  
   
     
     
         22 . A method of delivery of a nucleic acid molecule to intestinal tract cells of an individual comprising the steps of administering to said individual a pharmaceutical composition comprising: 
 a) a pharmaceutically acceptable carrier or diluent, and,    b) a composition comprising: 
 i) a ST receptor ligand; and  
 ii) a nucleic acid molecule.  
   
     
     
         23 . A method of treating an individual suspected of suffering from metastasized colorectal cancer comprising the steps of administering to said individual: 
 a) a conjugated compound comprising an ST receptor binding moiety and an enzyme; and    b) a prodrug which when processed by the enzyme is converted to a drug.    
     
     
         24 . The method of claims  23  wherein: 
 a) a conjugated compound comprises an ST receptor binding moiety and alkaline phosphatase; and    b) the prodrug is etoposidephosphate.    
     
     
         25 . The compound of  claim 1  wherein said active moiety is an enzyme.  
     
     
         26 . The compound of  claim 25  wherein said active moiety is alkaline phosphatase.