This is an archive of papers published by the staff and faculty of Fox Chase Cancer Center. For questions about content, please contact Talbot Research Library
Last updated on
George AJT , Jamar F , Tai MS , Heelan BT , Adams GP , McCartney JE , Houston LL , Weiner LM , Oppermann H , Peters AM , Huston JS
Radiometal Labeling of Recombinant Proteins by a Genetically- Engineered Minimal Chelation Site - Tc-99m Coordination by Single-Chain Fv Antibody Fusion Proteins through a C-Terminal Cysteinyl Peptide
Proceedings of the National Academy of Sciences of the United States of America. 1995 Aug 29;92(18) :8358-8362
AbstractWe describe a method to facilitate radioimaging with technetium-99m (Tc-99m) by genetic incorporation of a Tc-99m chelation site in recombinant single-chain Fv (sFv) antibody proteins, This method relies on fusion of the sFv C terminus with a Gly(4)Cys peptide that specifically coordinates Tc-99m, By using analogues of the 26-10 anti-digoxin sFv as our primary model, we find that addition of the chelate peptide, to form 26-10-1 sFv', does not alter the antigen-binding affinity of sFv, We have demonstrated nearly quantitative chelation of 0.5- 50 mCi of Tc-99m per mg of 26-10-1 sFv' (1 Ci = 37 GBq), These Tc-99m-labeled sFv' complexes are highly stable to challenge with saline buffers, plasma, or diethylenetriaminepentaacetic acid. We find that the Tc-99m-labeled 741F8-1 sFv', specific for the c-erbB-2 tumor-associated antigen, is effective in imaging human ovarian carcinoma in a scid mouse tumor xenograft model. This fusion chelate methodology should be applicable to diagnostic imaging with (TC)-T-99m and radioimmunotherapy with Re-186 or Re-188, and its use could extend beyond the sFv' to other engineered antibodies, recombinant proteins, and synthetic peptides.
NotesTimes Cited: 37 Article RR844 PROC NAT ACAD SCI USA