Her2 binders

Abstract

Imaging agents comprising an isolated polypeptide conjugated with a radionuclide and a chelator; wherein the isolated polypeptide binds specifically to HER2, or a variant thereof; and methods for preparing and using these imaging agents.

1 . An imaging agent composition comprising:
 an isolated polypeptide comprising SEQ. ID No 1, SEQ. ID No 2, or a conservative variant thereof, conjugated with a  99m Tc via a diaminedioxime chelator;   
       wherein the isolated polypeptide binds specifically to HER2, or a variant thereof. 
     
     
         2 . An imaging agent composition comprising:
 an isolated polypeptide comprising SEQ. ID No 1, SEQ. ID No 2, or a conservative variant thereof, conjugated with  67 Ga or  68 Ga via a NOTA chelator;   
       wherein the isolated polypeptide binds specifically to HER2, or a variant thereof. 
     
     
         3 . An imaging agent composition comprising:
 an isolated polypeptide comprising SEQ. ID No 1, SEQ. ID No 2, or a conservative variant thereof, conjugated with  18 F via a linker;   
       wherein the linker comprises a group derived from an aminoxy group, an azido group, or an alkyne group; and 
       wherein the isolated polypeptide binds specifically to HER2, or a variant thereof. 
     
     
         4 . The composition of  claim 1 , wherein the diaminedioxime chelator comprises Pn216, cPn216, Pn44, or derivatives thereof. 
     
     
         5 . The composition of  claim 3 , wherein the  18 F is attached to the isolated polypeptide via the aminoxy linker at (the) N-terminus of the isolated polypeptide. 
     
     
         6 . The composition of  claim 4 , wherein the  99m Tc is conjugated to the isolated polypeptide via the cPn216 chelator at (the) N-terminus of the isolated polypeptide. 
     
     
         7 . A method of imaging at least a portion of a subject comprising:
 administering the composition of  claim 1  to the subject, and   imaging the subject with a diagnostic device.   
     
     
         8 . The method of  claim 7 , further comprising the steps of:
 monitoring delivery of the composition of  claim 1  to the subject; and   diagnosing the subject with a HER2-associated disease condition.   
     
     
         9 . A method of imaging at least a portion of a subject comprising:
 administering the composition of  claim 2  to the subject, and   imaging the subject with a diagnostic device.   
     
     
         10 . The method of  claim 9 , further comprising the steps of:
 monitoring delivery of the composition of  claim 2  to the subject; and   diagnosing the subject with a HER2-associated disease condition.   
     
     
         11 . A method of imaging at least a portion of a subject comprising:
 administering the composition of  claim 3  to the subject, and   imaging the subject with a diagnostic device.   
     
     
         12 . The method of  claim 11 , further comprising the steps of:
 monitoring delivery of the composition of  claim 2  to the subject; and   diagnosing the subject with a HER2-associated disease condition.   
     
     
         13 . The method of  claim 12 , wherein the HER2-associated disease condition is breast cancer. 
     
     
         14 . The method of  claim 11 , wherein the diagnostic device employs an imaging method selected from the group consisting of MRI, PET, SPECT, radioimaging, and combinations thereof. 
     
     
         15 . A method for preparing a chelator conjugated polypeptide composition comprising:
 (i) providing an isolated polypeptide comprising SEQ. ID No 1 or SEQ. ID No 2, or a conservative variant thereof;   (ii) reacting a diaminedioxime chelator with the polypeptide to form the chelator conjugated polypeptide.   
     
     
         16 . The method of  claim 15 , wherein the diaminedioxime chelator is conjugated with  99m Tc. 
     
     
         17 . A method for preparing a  18 F conjugated polypeptide composition comprising:
 (i) providing an isolated polypeptide comprising SEQ. ID No. 1 or SEQ. ID No. 2 or a conservative variant thereof;   (ii) reacting the polypeptide with a linker wherein the linker comprises a group derived from an aminoxy group, an azido group, or an alkyne group; and   (iii) reacting the linker with a  18 F moiety to form the  18 F conjugated polypeptide.