Journal article

The Ionic Charge of Copper-64 Complexes Conjugated to an Engineered Antibody Affects Biodistribution

Jason LJ Dearing, Brett M Paterson, Vamsidhar Akurathi, Soledad Betanzos-Lara, S Ted Treves, Stephan D Voss, Jonathan M White, James S Huston, Suzanne V Smith, Paul S Donnelly, Alan B Packard

BIOCONJUGATE CHEMISTRY | AMER CHEMICAL SOC | Published : 2015

Abstract

The development of biomolecules as imaging probes requires radiolabeling methods that do not significantly influence their biodistribution. Sarcophagine (Sar) chelators form extremely stable complexes with copper and are therefore a promising option for labeling proteins with (64)Cu. However, initial studies using the first-generation sarcophagine bifunctional chelator SarAr to label the engineered antibody fragment ch14.18-ΔCH2 (MW 120 kDa) with (64)Cu showed high tracer retention in the kidneys, presumably because the high local positive charge on the Cu(II)-SarAr moiety resulted in increased binding of the labeled protein to the negatively charged basal cells of the glomerulus. To test th..

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Awarded by National Institutes of Health


Awarded by National Cancer Institute


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

The authors express their gratitude to Erin Snay, Patricia Dunning, and Kathryn G. Commons, Ph.D., for technical assistance. The ch14.18-Delta C<INF>H</INF>2 antibody was provided by Rupert Handgretinger, M.D., Universitat Tubingen (Germany); the original protein and production cell line were developed and made available for use by Stephen Gillies, Ph.D., Provenance Biopharmaceuticals (Billerica, MA). This work was supported by National Institutes of Health grant 5K08CA093554 (to S.D.V.), by the Comunidad de Madrid (through the Madrid-MIT M+Vision Fellowship, to J.L.J.D.), the Children's Hospital Radiology Foundation, the Australian Research Council (to P.S.D.), and a Victoria Fellowship from the Victorian Government (to B.M.P.). Copper-64 was produced at Washington University School of Medicine (St. Louis, MO, USA) under the support of National Cancer Institute grant R24CA86307.