Journal article

Macrobicyclic Cage Amine Ligands for Copper Radiopharmaceuticals: A Single Bivalent Cage Amine Containing Two Lys(3)-bombesin Targeting Peptides

Michelle T Ma, Margaret S Cooper, Rowena L Paul, Karen P Shaw, John A Karas, Denis Scanlon, Jonathan M White, Philip J Blower, Paul S Donnelly



The synthesis of new cage amine macrobicyclic ligands with pendent carboxylate functional groups designed for application in copper radiopharmaceuticals is described. Reaction of [Cu((NH(2))(2)sar)](2+) (sar = 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane) with either succinic or glutaric anhydride results in selective acylation of the primary amine atoms of [Cu((NH(2))(2)sar)](2+) to give derivatives with either one or two aliphatic carboxylate functional groups separated from the cage amine framework by either a four- or five-atom linker. The Cu(II) serves to protect the secondary amine nitrogen atoms from acylation, and can be removed to give the free ligands. The newly appended carboxylat..

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Funding Acknowledgements

The Australian Research Council is thanked for finacial support. M.T.M. acknowledges The Cancer Council Victoria for a Sydney Parker Smith Postdoctoral Cancer Research Fellowship, a Kaye Merlin Brutton Bequest and a Victoria Fellowship. R L.P. was supported by the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. M.S.C. and K.P.S. were supported by the KCL-UCL Comprehensive Cancer Imaging Centre, funded by Cancer Research U.K. & EPSRC, in association with the MRC and DoH (England).