Radiopharmaceutical and methods

Abstract

The radiopharmaceutical 177Lu-PSMA I&T is provided, including in high purities with extended shelf life. Further provided are methods of synthesis of 177Lu-PSMA I&T and pharmaceutical compositions and methods of treatment that comprise 177Lu-PSMA I&T.

1 - 70 . (canceled) 
     
     
         71 . A pharmaceutical composition comprising:
 (a) a complex of lutetium-177 and EuK-Sub-kf-iodo-y-DOTAGA;   (b) one or more ascorbate compounds.   
     
     
         72 . The composition of  claim 71  wherein the composition is free of a gentisate adduct impurity. 
     
     
         73 . The composition of  claim 71  wherein the composition comprises one or more gentisate compounds. 
     
     
         74 . The composition of  claim 71  wherein the composition is an aqueous formulation. 
     
     
         75 . The composition of  claim 71  wherein the complex of lutetium-177 and EuK-Sub-kf-iodo-y-DOTAGA comprises in optical excess the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         76 . The composition of  claim 71  wherein the complex of lutetium-177 and EuK-Sub-kf-iodo-y-DOTAGA comprises in optical excess the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         77 . A pharmaceutical composition comprising:
 (a) a complex of lutetium-177 and EuK-Sub-kf-iodo-y-DOTAGA;   (b) one or more stabilizer compounds,   wherein the composition at least substantially free of a gentisate acid adduct impurity.   
     
     
         78 . A method for treating a patient suffering from cancer, comprising:
 a) admixing 1) lutetium-177, 2) EuK-Sub-kf-iodo-y-DOTAGA in the substantial or complete absence of a gentisate compound, and 3) one or more stabilizer compounds;   b) heating the admixed 1) lutetium-177 and 2) EuK-Sub-kf-iodo-y-DOTAGA in the substantial or complete absence of a gentisate compound, wherein a complex of lutetium-177 and EuK-Sub-kf-iodo-y-DOTAGA is formed in the absence of a gentisate compound; and   c) administering the complex of lutetium-177 and EuK-Sub-kf-iodo-y-DOTAGA to the patient.   
     
     
         79 . The method of  claim 78  wherein the subject is suffering from prostate cancer. 
     
     
         80 . The method of  claim 78  wherein 1) lutetium-177, 2) EuK-Sub-kf-iodo-y-DOTAGA and 3) one or more stabilizer compounds are admixed in the absence of a gentisate compound. 
     
     
         81 . The method of  claim 78  wherein 1) lutetium-177, 2) EuK-Sub-kf-iodo-y-DOTAGA and 3) one or more stabilizer compounds are heated in the absence of a gentisate compound. 
     
     
         82 . The method of  claim 78  wherein one or more ascorbate compounds are admixed with 1) lutetium-177 and 2) EuK-Sub-kf-iodo-y-DOTAGA. 
     
     
         83 . The method of  claim 78  further comprising adding one or more ascorbate compounds to the complex of lutetium-177 and EuK-Sub-kf-iodo-y-DOTAGA. 
     
     
         84 . The method of  claim 83  wherein the one more gentisate compounds are added while or after heating is reduced or terminated. 
     
     
         85 . The method of  claim 78  further comprising adding one or more gentisate compounds to the complex of lutetium-177 and EuK-Sub-kf-iodo-y-DOTAGA. 
     
     
         86 . The method of  claim 83  further comprising adding one or more gentisate compounds to the complex of lutetium-177 and EuK-Sub-kf-iodo-y-DOTAGA. 
     
     
         87 . The method of  claim 85  wherein the one more gentisate compounds are added while or after heating is reduced or terminated. 
     
     
         88 . The method of  claim 86  wherein the one more gentisate compounds are added while or after heating is reduced or terminated. 
     
     
         89 . The method of  claim 80  wherein the complex of lutetium-177 and EuK-Sub-kf-iodo-y-DOTAGA does not contain an impurity having a relative retention time of approximately of 9 to 12 minutes by high-performance liquid chromatography. 
     
     
         90 . A complex of lutetium-177 and EuK-Sub-kf-iodo-y-DOTAGA obtainable by a method comprising:
 a) admixing 1) lutetium-177, 2) EuK-Sub-kf-iodo-y-DOTAGA in the substantial or complete absence of a gentisate compound, and 3) one or more stabilizer compounds; and   b) heating the admixed 1) lutetium-177 and 2) EuK-Sub-kf-iodo-y-DOTAGA in the substantial or complete absence of a gentisate compound, wherein a complex of lutetium-177 and EuK-Sub-kf-iodo-y-DOTAGA is formed in the absence of a gentisate compound.   
     
     
         91 . A pharmaceutical composition comprising a complex of  claim 90 . 
     
     
         92 . The pharmaceutical composition of  claim 91  wherein the complex comprising the following compound in optical excess: 
       
         
           
           
               
               
           
         
       
     
     
         93 . The pharmaceutical composition of  claim 91  wherein the complex comprising the following compound in optical excess: 
       
         
           
           
               
               
           
         
       
     
     
         94 . The pharmaceutical composition of  claim 91  wherein the composition comprises one or more stabilizer compounds. 
     
     
         95 . The pharmaceutical composition of  claim 91  wherein the composition comprises one or more ascorbate compounds. 
     
     
         96 . The pharmaceutical composition of  claim 95  wherein the composition comprises one or more gentisate compounds. 
     
     
         97 . The pharmaceutical composition of  claim 91  wherein the composition is free of a gentisate adduct impurity. 
     
     
         98 . A method of treating a subject suffering from cancer, comprising administering to the subject an effective amount of a composition of  claim 91 . 
     
     
         99 . The method of  claim 99  wherein the subject is suffering from prostate cancer.