Diphosphine Bioconjugates via Pt(0)-Catalyzed Hydrophosphination. A Versatile Chelator Platform for Technetium-99m and Rhenium-188 Radiolabeling of Biomolecules

Rachel E Nuttall, Truc Thuy Pham, Ailis C Chadwick, Ingebjørg N Hungnes, George Firth, Martin A Heckenast, Hazel A Sparkes, M Carmen Galan*, Michelle T Ma*, Paul G Pringle*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)


The ability to append targeting biomolecules to chelators that efficiently coordinate to the diagnostic imaging radionuclide, 99mTc, and the therapeutic radionuclide, 188Re, can potentially enable receptor-targeted "theranostic" treatment of disease. Here we show that Pt(0)-catalyzed hydrophosphination reactions are well-suited to the derivatization of diphosphines with biomolecular moieties enabling the efficient synthesis of ligands of the type Ph 2PCH 2CH 2P(CH 2CH 2-Glc) 2 ( L, where Glc = a glucose moiety) using the readily accessible Ph 2PCH 2CH 2PH 2 and acryl derivatives. It is shown that hydrophosphination of an acrylate derivative of a deprotected glucose can be carried out in aqueous media. Furthermore, the resulting glucose-chelator conjugates can be radiolabeled with either 99mTc(V) or 188Re(V) in high radiochemical yields (>95%), to furnish separable mixtures of cis- and trans-[M(O) 2 L 2] + (M = Tc, Re). Single photon emission computed tomography (SPECT) imaging and ex vivo biodistribution in healthy mice show that each isomer possesses favorable pharmacokinetic properties, with rapid clearance from blood circulation via a renal pathway. Both cis-[ 99mTc(O) 2 L 2] + and trans-[ 99mTc(O) 2 L 2] + exhibit high stability in serum. This new class of functionalized diphosphine chelators has the potential to provide access to receptor-targeted dual diagnostic/therapeutic pairs of radiopharmaceutical agents, for molecular 99mTc SPECT imaging and 188Re systemic radiotherapy.

Original languageEnglish
Pages (from-to)20582-20592
Number of pages11
JournalInorganic Chemistry
Issue number50
Early online date31 Jan 2023
Publication statusE-pub ahead of print - 31 Jan 2023

Bibliographical note

Funding Information:
This research was supported by a Cancer Research UK Career Establishment Award (C63178/A24959), the EPSRC programme for Next Generation Molecular Imaging and Therapy with Radionuclides (EP/S032789/1, “MITHRAS”), Rosetrees Trust (M685, M606), the Wellcome Multiuser Equipment Radioanalytical Facility funded by Wellcome Trust (212885/Z/18/Z), the Centre for Medical Engineering funded by the Wellcome Trust and the Engineering and Physical Sciences Research Council (EPSRC) (WT088641/Z/09/Z), the European Research Council grant number ERC–COG:648239, and the Bristol Chemical Synthesis Centre for Doctoral Training, funded by EPSRC (EP/L015366/1), and the University of Bristol, for a PhD studentship (to R.E.N.).We would like to thank Dr Paul J. Gates of the University of Bristol, UK for determining the mass spectra of the technetium complexes.

Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.

Structured keywords

  • BCS and TECS CDTs


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