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Enzyme mediated incorporation of zirconium-89 or copper-64 into a fragment antibody for same day imaging of epidermal growth factor receptor

Stacey E. Rudd, Jessica Van Zuylekom, Anna Raicevic, Lesley A. Pearce, Carleen Cullinane, Charlotte C. Williams, Timothy E. Adams, Rodney J. Hicks, Paul S. Donnelly

2021Chemical Science20 citationsDOIOpen Access PDF

Abstract

, were modified with a N-terminal glycine to enable them to act as substrates in sortase A mediated bioconjugation to the antibody fragment. Both fragments provided high-quality PET images of EGFR positive tumors in a mouse model at 3 hours post-injection, a significant advantage when compared to radiolabeled full antibodies that require several days between injection of the tracer and imaging. The use of enzymatic bioconjugation gives reproducible homogeneous products with the metal complexes selectively installed on the C-terminus of the antibody potentially simplifying regulatory approval.

Topics & Concepts

BioconjugationEpidermal growth factor receptorChemistryAntibodyPositron emission tomographyEpidermal growth factorEnzymeReceptorBiochemistryBiophysicsMolecular biologyMedicineNuclear medicineBiologyImmunologyBiochemical and Structural CharacterizationPeptidase Inhibition and AnalysisMonoclonal and Polyclonal Antibodies Research
Enzyme mediated incorporation of zirconium-89 or copper-64 into a fragment antibody for same day imaging of epidermal growth factor receptor | Litcius