Near infrared imaging agent

Abstract

This invention relates to an in-vivo diagnostic method based on near infrared radiation (NIR radiation) that uses water-soluble dyes and their biomolecule adducts, each having specific photophysical and pharmaco-chemical properties, as a contrast medium for fluorescence and transillumination diagnostics in the NIR range, to new dyes and pharmaceuticals containing such dyes.

1 - 8 . (canceled)  
     
     
         9 . An in-vivo diagnostic based on near infrared radiation, using compounds of the general formula I  
         B L -(F-W n ) m   (I)  
       wherein 
 L represents a number from 0 to 6,  
 n represents a number from 0 to 10, and  
 m represents a number from 1 to 100;  
 B is a biological detecting unit having a molecular weight of up to 30,000 that bonds to specific cell populations or selectively to receptors, or accumulates in tissues or tumours, or generally stays in the blood, or is a macromolecule that bonds non-selectively;  
 F represents a dye showing maximum absorption in the range of 650 to 1200 nm;  
 as well as their physiologically tolerable salts, characterized in that F within the general formula I represents a cyanine dye of the general formula IIa  
                     
 wherein  
 r represents the numbers 0, 1 or 2, wherein, for r=2, the respective L 6  and L 7  groups that occur in duplicate may be the same or different, L 1  to L 7  are the same or different, each independently representing a CH or CR group,  
 where  
 R is a halogen atom, a hydroxy, carboxy, acetoxy, amino, nitro, cyano or sulfonic acid group or an alkyl, alkenyl, hydroxyalkyl, carboxyalkyl, alkoxy, alkoxycarbonyl, sulfoalkyl, alkylamino, dialkylamino or halogenalkyl group containing up to 6 carbon atoms, an aryl, alkylaryl, hydroxyaryl, carboxyaryl, sulfoaryl, arylamino, diarylamino, nitroaryl or halogenaryl group containing up to 9 carbon atoms, or where R represents a bond that bonds to another group R and forms a 4- to 6-member ring together with the interspersed groups L 1  to L 7 , or two of L 1  to L 7  that are linked via a —CO— group,  
 R 3  to R 12  are the same or different, each independently representing a hydrogen atom, a group B as defined above or W as defined below, or an alkyl or alkenyl group containing up to 6 carbon atoms or an aryl or aralkyl group optionally carrying an additional group W as defined below, or with 5- to 6-member rings that may be saturated, unsaturated or aromatic, and that may optionally carry an additional group R as defined above, annelled to each pair of adjacent residue R 3  to R 10  with due regard for the interspersed C atoms,  
 X and Y are the same or different, each independently representing an O, S, Se or Te or a —C(CH 3 ) 2 —, —CH═CH— or —CR 13 R 14 — group,  
 where R 13  and R 14  independently represent a hydrogen atom, a group B as defined above or W as defined below, or an alkyl or alkenyl group containing up to 6 carbon atoms or an aryl or aralkyl group containing up to 9 carbon atoms, the alkyl, alkenyl, aryl or aralkyl group optionally carrying an additional group W as defined below,  
 characterized in that W within the general formula I is a carboxy or sulfonic acid group or a carboxyalkyl group or an alkoxycarbonyl or alkoxyoxoalkyl group containing up to 12 carbon atoms, and characterized in that W takes the position of R 4  and R 8  and/or R 6  and R 10  and/or R 11   and R 12 .  
 
     
     
         10 . A method of in-vivo diagnosis of disease comprising administering at least one of the compounds of  claim 9  to tissues and detecting said compound by means of near infrared radiation.  
     
     
         11 . An agent for in-vivo diagnosis comprising at least one of the cyanine dyes according to  claim 9  together with common adjuvants, substrates and diluants.