Journal article

PET imaging of tumours with a Cu-64 labeled macrobicyclic cage amine ligand tethered to Tyr(3)-octreotate

Brett M Paterson, Peter Roselt, Delphine Denoyer, Carleen Cullinane, David Binns, Wayne Noonan, Charmaine M Jeffery, Roger I Price, Jonathan M White, Rodney J Hicks, Paul S Donnelly



The use of copper radioisotopes in cancer diagnosis and radionuclide therapy is possible using chelators that are capable of binding Cu(II) with sufficient stability in vivo to provide high tumour-to-background contrast. Here we report the design and synthesis of a new bifunctional chelator, 5-(8-methyl-3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid (MeCOSar), that forms copper complexes of exceptional stability by virtue of a cage amine (sarcophagine) ligand and a new conjugate referred to as SarTATE, obtained by the conjugation of MeCOSar to the tumour-targeting peptide Tyr(3)-octreotate. Radiolabeling of SarTATE with (64)Cu(II), a radioisotope suitable for pos..

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Funding Acknowledgements

This work was partially supported by the Australian Research Council (PSD). Dr Matt Harris (Clarity Pharmaceuticals) is thanked for his support. We thank John A. Karas (Bio21 Institute, University of Melbourne) for guidance on peptide synthesis, and Kerry Ardley and Susan Jackson (Peter MacCallum Division of Molecular Imaging, Melbourne) for their technical contributions. The A427-7 cells were a kind donation from Prof Buck E. Rogers (Washington University, St Louis, MO). Professor Rod Hicks is a recipient of a translational research grant from the Victorian Cancer Agency which supported the in vitro and in vivo testing of this agent.