Technetium-dipyridine complexes, and methods of use thereof

Abstract

One aspect of the invention relates to novel complexes of technetium (Tc) with various heteroaromatic ligands, e.g., pyridyl and imidazolyl ligands, and their use in radiopharmaceuticals for a variety of clinical diagnostic and therapeutic applications. Another aspect of the invention relates to novel pyridyl ligands that form a portion of the aforementioned complexes. Methods for the preparation of the technetium complexes are also described. Another aspect of the invention relates to novel pyridyl ligands based on derivatized lysine, alanine and bis-amino acids for conjugation to small peptides by solid phase synthetic methods. Additionally, the invention relates to methods for imaging regions of a mammal using the complexes of the invention.

1 - 56 . (canceled) 
     
     
         57 . A compound represented by C: 
       
         
           
           
               
               
           
         
       
       wherein:
 L and L′ represent independently for each occurrence 2-methylenepyridyl, methylenecarboxylate, alkyl, aryl, or aralkyl; 
 at least one of L or L′ is methylenecarboxylate or 2-methylenepyridyl, and wherein the 2-methylenepyridyl is unsubstituted on the pyridyl ring or is substituted on the pyridyl ring with 1 to 4 instances of R′; 
 R′ is selected independently for each occurrence from the group consisting of halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, acyl, acyloxy, acylamino, silyloxy, amino, nitro, sulfhydryl, alkylthio, imino, amido, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, selenoalkyl, ketone, aldehyde, ester, heteroalkyl, cyano, guanidine, amidine, acetal, ketal, amine oxide, aryl, heteroaryl, aralkyl, heteroaralkyl, azido, aziridine, carbamoyl, epoxide, hydroxamic acid, imide, oxime, sulfonamide, thioamide, thiocarbamate, urea, thiourea, and —(CH 2 ) d —R 80 ; 
 R 80  represents independently for each occurrence carboxaldehyde, carboxylate, carboxamido, alkoxycarbonyl, aryloxycarbonyl, ammonium, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocyclyl, polycyclyl, amino acid, peptide, saccharide, ribonucleic acid, or (deoxy)ribonucleic acid; 
 d is an integer in the range 0 to 12 inclusive; 
 m is an integer in the range 0 to 6 inclusive; and 
 n is an integer in the range 0 to 6 inclusive. 
 
     
     
         58 . The compound of  claim 57 , wherein said compound IS complexed with a radionuclide. 
     
     
         59 . The compound of  claim 57 , wherein said compound is complexed with a radionuclide, wherein said radionuclide is technetium or rhenium. 
     
     
         60 . The compound of  claim 57 , wherein L is methylenecarboxylate; and L′ is alkyl. 
     
     
         61 . The compound of  claim 57 , wherein L is 2-methylenepyridyl; and L′ is alkyl. 
     
     
         62 . The compound of  claim 57 , wherein L is alkyl; and L′ is 2-methylene pyridyl. 
     
     
         63 . A formulation, comprising a compound according to  claim 57 ; and a pharmaceutically acceptable excipient. 
     
     
         64 . A method of imaging a region in a patient, comprising:
 administering to a patient a diagnostically effective amount of a compound of  claim 57 .; and   obtaining an image of said region of said patient.   
     
     
         65 . The method of  claim 64 , wherein said region of said patient is the head or thorax. 
     
     
         66 . A method of preparing a peptide conjugate incorporating a compound of  claim 57 , wherein the peptide conjugate is prepared using solid phase synthetic techniques.