A dual radiolabelling approach for tracking metal complexes: investigating the speciation of copper bis(thiosemicarbazonates) in vitro and in vivo

Metallomics : Integrated Biometal Science
Rebekka HuetingJ R Dilworth

Abstract

Copper(II)bis(thiosemicarbazonato) complexes such as [(64)Cu]Cu-ATSM continue to be investigated for positron emission tomography (PET) imaging of tumour hypoxia. However, the currently proposed mechanisms for the mode of action of these complexes are unable to account fully for their observed biological behaviour. In order to examine the roles of the copper metal and the ligand, we designed a pair of (123)I/(64)Cu-copper bis(thiosemicarbazonates), radiolabelled at either the metal or at the ligand. In vitro cellular retention studies of the orthogonal pair demonstrate for the first time that retention under hypoxia involves dissociation of the copper bis(thiosemicarbazone) complex, consistent with the previously suggested mechanism of reductive trapping of copper. In contrast, in vivo biodistribution and dynamic PET/SPECT imaging of the orthogonally labelled complexes underline our previous findings for [(64)Cu]Cu-ATSM and [(64)Cu]Cu-acetate, providing further support for the important contribution of copper metabolism in the in vivo hypoxia selectivity of Cu-ATSM. This dual radiolabelling approach may find applications for determining the speciation of other metal complexes in vitro and in vivo.

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Citations

Nov 20, 2015·Dalton Transactions : an International Journal of Inorganic Chemistry·Israt S AlamSofia I Pascu
May 7, 2016·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Fernando Cortezon-TamaritSofia I Pascu
Oct 18, 2019·Chembiochem : a European Journal of Chemical Biology·Mathieu L LepageDavid M Perrin
Aug 8, 2015·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Bruno L OliveiraPeter Caravan

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