Near Infrared Fluorescent Contrast Agent And Method For Fluorescence Imaging

Abstract

A near infrared fluorescent contrast agent which is excellent in permeability in a living tissue and enables specific imaging of tumor and/or blood vessel, comprising a compound represented by formula (I) or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 7 , and R 8 represent a C 1 -C 10 alkyl group or the like; R 3 , R 4 , R 5 , R 6 , R 9 , R 10 , R 11 , and R 12 represent a hydrogen atom, a C 1 -C 6 alkyl group, an aryl group or the like; X 1 and X 2 represent a C 1 -C 15 alkyl group or an aryl group and X 1 and X 2 in total have 0 to 4 carboxyl groups; m 1 , m 2 , and m 3 represents 0 or 1; L 1 to L 7 independently represent a methine group; M represents a hydrogen atom, a metal, or a quaternary ammonium salt; and n represents an integer of 1 to 7 necessary for neutralizing charge.

1 - 11 . (canceled) 
   
   
       12 . A near infrared fluorescent contrast agent comprising a pharmaceutically acceptable injectable carrier for diagnostic imaging and a compound of the following formula or a pharmaceutically acceptable salt thereof: 
     
       
         
         
             
             
         
       
     
     wherein
 R 1 , R 2 , R 7 , and R 8  independently represent a substituted or unsubstituted C 1 -C 10  alkyl group or a substituted or unsubstituted aryl group; or 
 R 1  and R 2  and/or R 7  and R 8  bind to each other to form a ring; 
 R 3 , R 4 , R 5 , R 6 , R 9 , R 10 , R 11  and R 12  independently represent a hydrogen atom, a substituted or unsubstituted C 1 -C 6  alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a halogen atom, cyano group, carboxyl group, or sulfo group; or two of R 3 , R 4 , R 5 , R 6 , R 9 , R 10 , R 11  and R 12  bind to each other to form a ring; 
 X 2  represents a substituted or unsubstituted C 1 -C 15  alkyl group or a substituted or unsubstituted aryl group; 
 X 1  is a group represented by the following formula 
 
     
       
         
         
             
             
         
       
     
     wherein
 X 1  and X 2  in total have 2 or 4 carboxyl groups; 
 Y 1  and Y 2  independently represent a substituted or unsubstituted divalent linking group; 
 m 1  represents 0 or 1; 
 m 2  represents or 1; 
 m 3  represents 0 or 1; 
 L 1 , L 2 , L 3 , L 4 , L 5 , L 6 , and L 7  independently represent a substituted or unsubstituted methine group, provided that when two or more of the methine groups have substituents, the substituents bind to each other to form a ring; 
 M represents a hydrogen atom, a metal, or a quaternary ammonium salt; and 
 n represents an integer of 1 to 7 necessary for neutralizing charge. 
 
   
   
       13 . The near infrared fluorescent contrast agent according to  claim 12 , wherein each of m 1 , m 2 , and m 3  is 1. 
   
   
       14 . The near infrared fluorescent contrast agent according to  claim 12 , wherein X 1  and X 2  independently represent a group represented by the following formula: 
     
       
         
         
             
             
         
       
     
     wherein Y 1  and Y 2  independently represent a substituted or unsubstituted divalent bond. 
   
   
       15 . The near infrared fluorescent contrast agent according to  claim 12 , wherein at least one of R 3 , R 4 , R 5 , R 6 , R 9 , R 10 , R 11 , and R 12  is a substituted or unsubstituted aryl group or a substituted or unsubstituted heteroaryl group. 
   
   
       16 . The near infrared fluorescent contrast agent according to  claim 12 , wherein
 Y 1  represents —(CH 2 ) p CONH—,   p represents an integer of 1 to 4, and   Y 2  represents —(CH 2 )— or (CH 2 ) 2 —.   
   
   
       17 . The near infrared fluorescent contrast agent according to  claim 12 , wherein the pharmaceutically acceptable injectable carrier for diagnostic imaging is injectable distilled water. 
   
   
       18 . The near infrared fluorescent contrast agent according to  claim 12 , wherein the pharmaceutically acceptable injectable carrier for diagnostic imaging is physiological saline. 
   
   
       19 . The near infrared fluorescent contrast agent according to  claim 12 , wherein the pharmaceutically acceptable injectable carrier for diagnostic imaging is Ringer's solution. 
   
   
       20 . The near infrared fluorescent contrast agent according to  claim 12 , wherein at least one of R 3 , R 4 , R 5 , R 6 , R 9 , R 10 , R 11 , and R 12  is a substituted or unsubstituted aryl group. 
   
   
       21 . The near infrared fluorescent contrast agent according to  claim 12 , wherein at least one of R 3 , R 4 , R 5 , R 6 , R 9 , R 10 , R 11 , and R 12  is a substituted or unsubstituted heteroaryl group. 
   
   
       22 . The near infrared fluorescent contrast agent according to  claim 12 , wherein Y 1  represents —(CH 2 ) p CONH—. 
   
   
       23 . The near infrared fluorescent contrast agent according to  claim 12 , wherein p represents an integer of 1 to 4. 
   
   
       24 . The near infrared fluorescent contrast agent according to  claim 12 , wherein Y 2  represents —(CH 2 )— or (CH 2 ) 2 —. 
   
   
       25 . The near infrared fluorescent contrast agent according to  claim 14 , wherein each of m 1 , m 2 , and m 3  is 1. 
   
   
       26 . The near infrared fluorescent contrast agent according to  claim 16 , wherein each of m 1 , m 2 , and m 3  is 1.