Complex Compound and MRI Probe Made of Same

Abstract

Novel gadolinium complex compounds responsive to ions and compounds other than zinc ion, as well as MRI probes made of the compounds are disclosed. Since the gadolinium complex compounds of the present invention such as that represented by the following structural formula exhibit responsiveness to potassium ion, calcium ion, glucose or the like, by using the gadolinium complex compounds of the present invention as a MRI probe, the ion or compound in a living body can be detected and concentration distribution thereof may be determined.

1 . A gadolinium complex compound represented by the following Formula (1) or (2): 
       
         
           
           
               
               
           
         
       
       (wherein in Formulae (1) and (2), R 1  and R 2  are independently a group represented by any of the following Formulae (3), (4), (5), (6) and (7); R 3 , R 4 , R 5  and R 6  are independently —OH or a group represented by any of the following Formulae (3), (4), (5), (6) and (7) with the proviso that two of R 3 , R 4 , R 5  and R 6  are —OH and the other two of them are independently a group represented by any of the following Formulae (3), (4), (5), (6) and (7): 
       
         
           
           
               
               
           
         
       
       (wherein in Formulae (3), (4), (5), (6) and (7), X is an alkylene group (wherein one or more carbon atoms constituting the alkylene chain may be an oxygen atom(s), nitrogen atom(s), sulfur atom(s), silicon atom(s), phosphorus atom(s) or carbonyl group(s))
 m is 1 or 2; n is an integer of 1 to 8; 
 Y is a nitrogen atom, sulfur atom or ═CH—; 
 Z 1 , Z 2  and Z 3  are independently an oxygen atom, nitrogen atom or sulfur atom; 
 E 1 , E 2 , E 3 , E 4 , E 5 , E 6 , E 7 , E 8 , E 9 , E 10 , E 11  and E 12  are independently a hydrogen atom or an alkyl group (wherein one or more carbon atoms constituting the alkyl chain may be an oxygen atom(s), nitrogen atom(s), sulfur atom(s), silicon atom(s) or phosphorus atom(s)), wherein E 1 , E 2 , E 3  and E 4  may together form a benzene ring, E 5 , E 6 , E 7  and E 8  may together form a benzene ring, and E 9 , E 10 , E 11  and E 12  may together form a benzene ring; 
 “A”s are independently a hydrogen atom or fluorine atom; 
 W is —OCH 3 , a hydrogen atom or fluorine atom). 
 
     
     
         2 . The gadolinium complex compound according to  claim 1 , wherein in said Formulae (1) and (2), R 1  and R 2  are independently a group represented by said Formula (3) or (4); two of R 3 , R 4 , R 5  and R 6  are —OH and the other two of them are independently a group represented by said Formula (3) or (4). 
     
     
         3 . The gadolinium complex compound according to  claim 1 , wherein in said Formulae (1) and (2), R 1  and R 2  are independently a group represented by said Formula (4); two of R 3 , R 4 , R 5  and R 6  are —OH and the other two of them are independently a group represented by said Formula (4); in said Formula (4), E 1 , E 2 , E 3 , E 4 , E 5 , E 6 , E 7 , E 8 , E 9 , E 10 , E 11  and E 12  are hydrogen atoms; X is a C 1 -C 10  alkylene group (wherein one or more carbon atoms constituting the alkylene chain may be an oxygen atom(s), nitrogen atom(s), sulfur atom(s), silicon atom(s), phosphorus atom(s) or carbonyl group(s)); and wherein Z 1 , Z 2  and Z 3  are oxygen atoms. 
     
     
         4 . The gadolinium complex compound according to  claim 3 , wherein said group represented by said Formula (4) is a group represented by the following Formula (8) or (9): 
       
         
           
           
               
               
           
         
       
     
     
         5 . The gadolinium complex compound according to any one of  claims 2  to  4 , which is represented by said Formula (1). 
     
     
         6 . The gadolinium complex compound according to  claim 1 , wherein in said Formulae (1) and (2), R 1  and R 2  are independently a group represented by said Formula (5); two of R 3 , R 4 , R 5  and R 6  are —OH and the other two of them are independently a group represented by said Formula (5). 
     
     
         7 . The gadolinium complex compound according to  claim 6 , wherein in said Formula (5), X is a C 1 -C 10  alkylene group (wherein one or more carbon atoms constituting the alkylene chain may be an oxygen atom(s), nitrogen atom(s), sulfur atom(s), silicon atom(s), phosphorus atom(s) or carbonyl group(s)). 
     
     
         8 . The gadolinium complex compound according to  claim 7 , wherein said group represented by said Formula (5) is a group represented by the following Formula (10): 
       
         
           
           
               
               
           
         
       
     
     
         9 . The gadolinium complex compound according to any one of  claims 6  to  8 , which is represented by said Formula (1). 
     
     
         10 . The gadolinium complex compound according to  claim 1 , wherein in said Formulae (1) and (2), R 1  and R 2  are independently a group represented by said Formula (6) or (7); two of R 3 , R 4 , R 5  and R 6  are —OH and the other two of them are independently a group represented by said Formula (6) or (7). 
     
     
         11 . The gadolinium complex compound according to  claim 10 , wherein in said Formula (6) or (7), X is a C 1 -C 10  alkylene group (wherein one or more carbon atoms constituting the alkylene chain may be an oxygen atom(s), nitrogen atom(s), sulfur atom(s), silicon atom(s), phosphorus atom(s) or carbonyl group(s)). 
     
     
         12 . The gadolinium complex compound according to  claim 11 , wherein in said Formulae (1) and (2), R 1  and R 2  are independently a group represented by said Formula (7); two of R 3 , R 4 , R 5  and R 6  are —OH and the other two of them are independently a group represented by said Formula (7). 
     
     
         13 . The gadolinium complex compound according to  claim 12 , wherein said group represented by said Formula (7) is a group represented by the following Formula (11): 
       
         
           
           
               
               
           
         
       
       (wherein in Formula (11), p is an integer of 2 or 3). 
     
     
         14 . The gadolinium complex compound according to any one of  claims 10  to  13 , which is represented by said Formula (1). 
     
     
         15 . An MRI probe consisting essentially of said gadolinium complex compound according to any one of  claims 1  to  14 . 
     
     
         16 . A potassium ion-responsive MRI probe consisting essentially of said gadolinium complex compound according to any one of  claims 2  to  5 . 
     
     
         17 . A calcium ion-responsive MRI probe consisting essentially of said gadolinium complex compound according to any one of  claims 6  to  9 . 
     
     
         18 . A glucose-responsive MRI probe consisting essentially of said gadolinium complex compound according to any one of  claims 10  to  14 . 
     
     
         19 . Use of said gadolinium complex compound according to any one of  claims 1  to  14  for the production of an MRI probe. 
     
     
         20 . Use of said gadolinium complex compound according to any one of  claims 2  to  5  for the production of a potassium ion-responsive MRI probe. 
     
     
         21 . Use of said gadolinium complex compound according to any one of  claims 6  to  9  for the production of a calcium ion-responsive MRI probe. 
     
     
         22 . Use of said gadolinium complex compound according to any one of  claims 10  to  14  for the production of a glucose-responsive MRI probe. 
     
     
         23 . A method for measuring potassium ion, calcium ion or glucose in a living body, said method comprising administering said MRI probe according to  claim 15  to said living body. 
     
     
         24 . A method for measuring potassium ion in a living body, said method comprising administering said potassium ion-responsive MRI probe according to  claim 16  to said living body. 
     
     
         25 . A method for measuring calcium ion in a living body, said method comprising administering said calcium ion-responsive MRI probe according to  claim 17  to said living body. 
     
     
         26 . A method for measuring glucose ion in a living body, said method comprising administering said glucose-responsive MRI probe according to  claim 18  to said living body.