Method for the diagnosis and treatment of inflammation

Abstract

PCT No. PCT/US87/00079 Sec. 371 Date Nov. 13, 1987 Sec. 102(e) Date Nov. 13, 1987 PCT Filed Jan. 12, 1987 PCT Pub. No. WO87/04351 PCT Pub. Date Jul. 30, 1987.The invention relates to a method of detecting an inflammation site in an individual by administering to the individual a diagnostically effective amount of detectably labeled immunoglobulin or fragment thereof, wherein the immunoglobulin substantially accumulates at the site when the site is inflamed.

What is new and is desired to be covered by letters patent is: 
     
       1. A method of detecting an inflammation site in vivo in an individual which comprises: (a) administering to said individual a diagnostically effective amount of .[.a.]. .Iadd.an .Iaddend.agent wherein said agent .[.consists essentially of.]. .Iadd.comprises .Iaddend.a detachably labeled immunoglobulin or .[.a.]. .Iadd.an Fc .Iaddend.fragment .Iadd.or subfragment .Iaddend.thereof, and said immunoglobulin.Iadd., or Fc fragment or subfragment thereof, .Iaddend.substantially accumulates at said site when said site is inflamed .Iadd.and said agent has no substantial epitopic specificity for said inflamed site.[.,.]..Iadd.; .Iaddend.and   (b) detecting said .[.detectably labeled immunoglobulin.]. .Iadd.agent.Iaddend..   
     
     
       2. The method of claim 1 wherein said .[.immunoglobulin.]. .Iadd.agent .Iaddend.does not accumulate at said site when said site is not inflamed. 
     
     
       3. The method of claim 1 wherein said .[.immunoglobulin.]. .Iadd.agent .Iaddend.is .[.monoclonally derived.]. .Iadd.one or more detectably labeled monoclonal antibodies. .Iaddend. 
     
     
       4. The method of claim 1 wherein said .[.immunoglobulin.]. .Iadd.agent .Iaddend.is .[.polyclonally derived.]. .Iadd.detectably labeled, pooled, human immunoglobulin.Iaddend.. 
     
     
       5. The method as in any one of claims 1-4, wherein said detectable label is a radioactive isotope. 
     
     
       6. The method of claim 5, wherein said isotope is selected from the group consisting of  99m  Tc,  123  I,  131  I,  111  In,  97  Ru,  67  Cu,  67  Ga,  68  Ga,  72  As,  89  Zr, and  201  Tl. 
     
     
       7. The method as in any one of claims 1-4, wherein said detectable label is a paramagnetic label. 
     
     
       8. The method of claim 7, wherein said paramagnetic label is selected from the group consisting of  157  Gd,  55  Mn,  162  Dy,  52  Cr, and  56  Fe. 
     
     
       9. The method of claim 7, wherein said detecting is by magnetic resonance imaging or positron emission tomography. 
     
     
       10. The method of claim 1, wherein said administration is parenteral. 
     
     
       11. The method of claim 10, wherein said parenteral administration is by intradermal, subcutaneous, intramuscular, intraperitoneal, or intravenous injection. 
     
     
       12. The method of claim 10, wherein said administration is by gradual perfusion. 
     
     
       13. The method of claim 12, wherein said gradual perfusion is by intravenous or peristaltic means. 
     
     
       14. A method of detecting the underlying cause of an inflammatory response in vivo in an individual which comprises: (a) administering to said individual a diagnostically effective amount of .Iadd.a first agent, wherein said first agent comprises .Iaddend.a detectably labeled.Iadd., non-specific .Iaddend.immunoglobulin or .[.a.]. .Iadd.an Fc .Iaddend.fragment .Iadd.or subfragment .Iaddend.thereof, .Iadd.and .Iaddend.wherein said immunoglobulin .Iadd.or Fc fragment or subfragment .Iaddend.substantially accumulates at said site when said site is inflamed;   (b) imaging said individual to detect the presence of a site of inflammation;   (c) based on the presence of a site of inflammation as demonstrated by step (b), further administering to said individual a diagnostically effective amount of a detectably labeled specific antibody or a fragment thereof, wherein said detectably labeled specific antibody .Iadd.or fragment thereof .Iaddend.can .Iadd.specifically .Iaddend.bind to the underlying cause of the inflammatory response; and   (d) imaging said individual to detect the presence of the detectable labeled specific antibody or fragment thereof bound to the underlying cause of the inflammation at the site of the inflammation.   
     
     
       15. The method of claim 14 which further comprises: treating the underlying cause of the inflammatory response therapeutically with an appropriate agent. 
     
     
       16. The method of claim 15, wherein said treating utilizes a therapeutically labeled antibody specific for said underlying cause of the inflammatory response, bound to said agent. 
     
     
       17. The method of claim 14, wherein said specific antibody is .[.monoclonally derived.]. .Iadd.a monoclonal antibody.Iaddend.. 
     
     
       18. The method of claim 15, wherein said specific antibody is .[.polyclonally derived.]. .Iadd.a polyclonal antibody.Iaddend.. 
     
     
       19. The method as in any one of claims 15-16, wherein said agent is a drug. 
     
     
       20. The method as in any one of claims 15-16, wherein said agent is a lectin. 
     
     
       21. The method of claim 20, wherein said lectin is the alpha-chain of ricin. 
     
     
       22. The method as in any one of claims 15-16, wherein said agent is a toxin. 
     
     
       23. The method of claim 22, wherein said toxin is diphtheria toxin. 
     
     
       24. The method as in any one of claims 15-16, wherein said agent is a radioactive isotope. 
     
     
       25. The method of claim 24, wherein said radioactive isotope is selected from the group consisting of  125  I,  131  I,  90  Y,  67  Cu,  217  Bi,  211  At,  212  Pb,  47  Sc, or  109  Pd. 
     
     
       26. The method as in any one of claims 15-16, wherein said agent is an antimicrobial. 
     
     
       27. The method of claim 26, wherein said antimicrobial is selected from the group consisting of an anti-bacterial, an anti-fungal, an anti-viral, and an anti-parasitic. 
     
     
       28. The method of claim 1 or 14, wherein said individual is a human. 
     
     
       29. The method of claim 1 or 14, wherein said inflammation is a result of a microbial infection, a viral infection, a trauma, an autoimmune process, or a tumor. .Iadd. 
     
     
       30.  A method of detecting an inflammation site in vivo in an individual which comprises: (a) administering to said individual a diagnostically effective amount of an agent wherein said agent comprises a detachably labeled immunoglobulin or an Fc fragment or subfragment thereof, and said immunoglobulin, or Fc fragment or subfragment thereof, substantially accumulates at said site when said site is inflamed wherein said accumulation is substantially independent of the epitopic specificity of the immunoglobulin; and   (b) detecting said agent..Iaddend. .Iadd.   
     
     
       31.  The method of claim 30, wherein said agent is one or more detectably labeled monclonal antibodies..Iaddend. .Iadd.32. The method of claim 3, wherein said one or more detectably labeled monoclonal antibodies are murine monoclonal antibodies..Iaddend. .Iadd.33. The method of claim 17, wherein said monoclonal antibody is a murine monoclonal antibody..Iaddend. .Iadd.34. The method of claim 31, wherein said monoclonal antibody is a murine monoclonal antibody..Iaddend.