Journal article

Bifunctional Cu-64-labelled macrobicyclic cage amine isothiocyanates for immuno-positron emission tomography

Brett M Paterson, Gojko Buncic, Lachlan E McInnes, Peter Roselt, Carleen Cullinane, David S Binns, Charmaine M Jeffery, Roger I Price, Rodney J Hicks, Paul S Donnelly

Dalton Transactions | ROYAL SOC CHEMISTRY | Published : 2015


New macrobicyclic cage amine or "sarcophagine" (sar) bifunctional chelators have been synthesised that form copper complexes of exceptional in vivo stability and incorporate isothiocyanate (-NCS) functional groups for conjugation to an antibody. The chelators were synthesised from the methyl-capped complex [Mg(II)(CH3)(NH2)sar](2+). Coordination of Mg(II) within the cavity of the cage amine ligand protects the secondary amine atoms from reacting with the -NCS functional groups. Two different [Mg(II)(NCS-sar)](2+) derivatives were conjugated to the HER2/neu-targeting antibody trastuzumab and the progress of the reaction monitored by electrospray mass spectrometry. The Mg(II) ion was removed f..

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Funding Acknowledgements

This work was partially supported by the Australian Research Council (PSD). BMP acknowledges a Kaye Merlin Brutton Bequest from the University of Melbourne and a Victorian Postdoctoral Research Fellowship from the Victorian Government. We thank Wayne Noonan (Peter MacCallum Cancer Centre, Melbourne) for assistance with radiochemistry and Kerry Ardley, Rachael Walker and Susan Jackson (Research Division, Peter MacCallum Cancer Centre, Melbourne) for their technical contributions. Dr Matt Harris (Clarity Pharmaceuticals) is thanked for his support.