Journal article
Enzyme mediated incorporation of zirconium-89 or copper-64 into a fragment antibody for same day imaging of epidermal growth factor receptor
SE Rudd, JK Van Zuylekom, A Raicevic, LA Pearce, C Cullinane, CC Williams, TE Adams, RJ Hicks, PS Donnelly
Chemical Science | ROYAL SOC CHEMISTRY | Published : 2021
DOI: 10.1039/d1sc01422f
Abstract
Identification of tumors which over-express Epidermal Growth Factor Receptor (EGFR) is important in selecting patients for anti-EGFR therapies. Enzymatic bioconjugation was used to introduce positron-emitting radionuclides (89Zr,64Cu) into an anti-EGFR antibody fragment for Positron Emission Tomography (PET) imaging the same day as injection. A monovalent antibody fragment with high affinity for EGFR was engineered to include a sequence that is recognized by the transpeptidase sortase A. Two different metal chelators, one for89ZrIVand one for64CuII, were modified with a N-terminal glycine to enable them to act as substrates in sortase A mediated bioconjugation to the antibody fragment. Both ..
View full abstractGrants
Funding Acknowledgements
Funding from the Australian Research Council and the National Health and Medical Research Council. The G8 PET/CT scanner was purchased with the support of a grant from the Australian Cancer Research Foundation. We thank the Mass Spectrometry and Proteomics Facility at Bio21 Institute, University of Melbourne. We also thank Professor Roger I. Price, Dr Ali Asad and Thien Dinh for provision of <SUP>89</SUP>Zr/<SUP>64</SUP>Cu. Susan Jackson and Rachael Walker for expert technical assistance with mouse models, Stewart Nuttall for pET28a-FLAG vector, Stephan Eckert and Laura Castelli for help with vector cloning, the Fermentation Team (National Biologics Facility) for scale-up cell culture and transfections, Jo Caine for help with protein purification, and Dr Mark Richardson for assistance with figures. The National Biologics Facility is supported by Therapeutic Innovation Australia through the National Collaborative Research Infrastructure Strategy.