Formulations and kits for radiotherapy and diagnostic imaging

Abstract

Aqueous formulations and kits of radiopharmaceutical compounds of general Formula (II) protected from radiolysis with stabilisers, such as L-methionine and gentisic acid, are disclosed, wherein the compounds are based on sarcophagine ligands coordinated to a radioisotope, such as 64-copper, and linked to a tetrazine group for reaction with tumour targeting antibodies having functional reactive groups such as trans-cyclooctene, processes of preparing said radioligand formulations, and uses thereof for radioimaging, diagnosing and treating cancer.

What is claimed is: 
     
         1 . A kit comprising a compound of Formula (II), or a pharmaceutically acceptable salt thereof, complexed with a Cu ion: 
       
         
           
           
               
               
           
         
       
       the kit comprising:
 a container comprising a compound of Formula (II), or a pharmaceutically acceptable salt thereof; 
 a container comprising a solution of a Cu ion; 
 a container comprising about 4% (v/v) to about 10% (v/v) ethanol and about 0.5% (v/v) to about 0.7% (w/v) sodium gentisate; and 
 a container comprising about 4% (v/v) to about 10% (v/v) ethanol and about 0.6% to about 1.2% (w/v) sodium chloride; and 
 instructions for preparing an aqueous formulation of a compound of Formula (II), or a salt thereof, complexed with a Cu ion, 
 wherein: 
 R 1  is H, optionally substituted alkyl or optionally substituted amino; and 
 R 2 , R 3  and R 4  are linker groups; and 
 R 5  is H, optionally substituted alkyl, optionally substituted aryl or optionally substituted heteroaryl. 
 
     
     
         2 . The kit according to  claim 1 , further including the addition of L-methionine, or a salt thereof. 
     
     
         3 . The kit according to  claim 1 , wherein the compound of Formula (II), or a salt thereof, is lyophilized. 
     
     
         4 . The kit according to  claim 1 , wherein R 1  is CH 3  or NH 2 . 
     
     
         5 . The kit according to  claim 1 , wherein R 2  comprises a benzylene group. 
     
     
         6 . The kit according to  claim 1 , wherein R 2  comprises an aminobenzylene group. 
     
     
         7 . The kit according to  claim 1 , wherein R 3  comprises a propylene group. 
     
     
         8 . The kit according to  claim 1 , wherein R 2  comprises a benzylene group and R 3  comprises a propylene group. 
     
     
         9 . The kit according to  claim 1 , wherein R 4  comprises a phenylene group. 
     
     
         10 . The kit according to  claim 1 , wherein the compound of Formula (II) is: 
       
         
           
           
               
               
           
         
       
     
     
         11 . The kit according to  claim 1 , wherein the compound of Formula (II) is: 
       
         
           
           
               
               
           
         
       
     
     
         12 . The kit according to  claim 1 , wherein the Cu ion is a radioisotope. 
     
     
         13 . The kit according to  claim 12 , wherein the Cu ion is a radioisotope selected from the group consisting of  60 Cu,  64 Cu and  67 Cu. 
     
     
         14 . The kit according to  claim 1 , wherein the kit further comprises a container of a compound that can bind to a tumour or cancer site and comprises a functional group that reacts with a tetrazine moiety of the compound of Formula (II).