Matrix metalloproteinase inhibitors

Abstract

Thus the present invention describes diagnostic agents comprising a diagnostic metal and a compound, wherein the compound comprises: 1-10 targeting moieties; a chelator; and 0-1 linking groups between the targeting moiety and chelator; wherein the targeting moiety is a matrix metalloproteinase inhibitor; and wherein the chelator is capable of conjugating to the diagnostic metal. The present invention also provides novel compositions of the compounds of the invention, kits, and their uses in diagnosis of diseases associated with MMPs.

1 - 103 . (canceled)  
     
     
         104 . A method of detecting, imaging or monitoring congestive heart failure in a patient, comprising the steps of: 
 administering a diagnostic agent to the patient; and    acquiring an image of a site of concentration of the diagnostic agent in the patient by a diagnostic imaging technique;    wherein the diagnostic agent comprises a matrix metalloproteinase inhibitor and an imaging moiety conjugated to said matrix metalloproteinase inhibitor; and    wherein said imaging moiety is a gamma ray radioisotope, a positron emitting radioisotope, a magnetic resonance imaging contrast agent, an x-ray contrast agent, or an ultrasound contrast agent.    
     
     
         105 . A method of detecting, imaging or monitoring congestive heart failure in a patient according to  claim 104 , 
 wherein the diagnostic agent comprises an imaging moiety and a compound of the formula:      (Q) d -(L n ) x″ -K    or a pharmaceutically acceptable salt thereof;    wherein    Q is a matrix metalloproteinase inhibitor;    L n  is an optional linking group;    K is a chelator or a surfactant capable of forming an echogenic gas filled lipid sphere or microbubble;    d is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and    x″ is 0 or 1.    
     
     
         106 . A method of detecting, imaging or monitoring congestive heart failure in a patient according to  claim 105 , 
 wherein d is 1, 2, 3, 4, or 5.    
     
     
         107 . A method of detecting, imaging or monitoring congestive heart failure in a patient according to  claim 105 , 
 wherein d is 1, 2, or 3.    
     
     
         108 . A method of detecting, imaging or monitoring congestive heart failure in a patient according to  claim 105 , 
 wherein d is 1 or 2.    
     
     
         109 . A method of detecting, imaging or monitoring congestive heart failure in a patient according to  claim 105 , 
 wherein d is 1.    
     
     
         110 . A method of detecting, imaging or monitoring congestive heart failure in a patient according to  claim 105 , 
 wherein x″ is 0.    
     
     
         111 . A method of detecting, imaging or monitoring congestive heart failure in a patient according to  claim 105 , 
 wherein x″ is 1.    
     
     
         112 . A method according to  claim 104 , 
 wherein said imaging moiety is a paramagnetic metal, a ferromagnetic metal, a gamma-emitting radioisotope, positron-emitting radioisotope, or an x-ray absorber.    
     
     
         113 . A method according to  claim 104 , 
 wherein said imaging moiety is  99m Tc,  95 Tc,  111 In,  62 Cu,  64 Cu,  67 Ga, or  68 Ga.    
     
     
         114 . A method according to  claim 104 , 
 wherein said imaging moiety is  99     m   Tc.    
     
     
         115 . A method according to  claim 104 , 
 wherein said imaging moiety is  111 In.    
     
     
         116 . A method according to  claim 104 , 
 wherein said imaging moiety is Gd(III), Dy(III), Fe(III), or Mn(II).    
     
     
         117 . A method according to  claim 104 , 
 wherein said imaging moiety is Re, Sm, Ho, Lu, Pm, Y, Bi, Pd, Gd, La, Au, Au, Yb, Dy, Cu, Rh, Ag, and Ir.    
     
     
         118 . A method according to  claim 104 , 
 wherein said imaging moiety is a perfluorocarbon gas or sulfur hexafluoride.    
     
     
         119 . A method according to  claim 118 , 
 wherein said perfluorocarbon gas is perfluoromethane, perfluoroethane, perfluoropropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, or perfluorohexane.