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One-step, kit-based radiopharmaceuticals for molecular SPECT imaging: a versatile diphosphine chelator for 99mTc radiolabelling of peptides

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Pages (from-to)16156-16165
Number of pages10
JournalDalton Transactions
Issue number44
Early online date15 Oct 2021
Accepted/In press15 Oct 2021
E-pub ahead of print15 Oct 2021
Published28 Nov 2021

Bibliographical note

Funding Information: This research was supported by a Cancer Research UK Career Establishment Award (C63178/A24959), King’s College London & Imperial College London EPSRC Centre for Doctoral Training in Medical Imaging (EP/L015226/1), 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), and the Centre for Medical Engineering funded by the Wellcome Trust and the Engineering and Physical Sciences Research Council (WT088641/Z/09/Z), and the King’s College London Centre for Biomolecular Spectroscopy funded by Wellcome Trust (202762/Z/16/Z) and British Heart Foundation (IG/16/2/32273). Publisher Copyright: © 2021 The Royal Society of Chemistry.

King's Authors


Radiotracers labelled with technetium-99m (99mTc) enable accessible diagnostic imaging of disease, provided that radiotracer preparation is simple. Whilst 99mTc radiopharmaceuticals for imaging perfusion are routinely prepared from kits, and regularly used in healthcare, there are no 99mTc-labelled receptor-targeted radiopharmaceuticals in widespread clinical use. This is in part due to the multistep radiosyntheses required for the latter. We demonstrate that the diphosphine, 2,3-bis(diphenylphosphino)maleic anhydride (BMA), is an excellent platform for preparation of kit-based, receptor-targeted 99mTc-labelled radiotracers: its conjugates are simple to prepare and can be easily labelled with 99mTc using one-step, kit-based protocols. Here, reaction of BMA with the αvβ3-integrin receptor targeted cyclic peptide, Arg-Gly-Asp-DPhe-Lys (RGD), provided the first diphosphine-peptide conjugate, DP-RGD. DP-RGD was incorporated into a “kit”, and addition of a saline solution containing 99mTcO4- to this kit, followed by heating, furnished the radiotracer [99mTcO2(DP-RGD)2]+ in consistently high radiochemical yields (> 90%). The analogous [ReO2(DP-RGD)2]+ compound was prepared and characterised, revealing that both [99mTcO2(DP-RGD)2]+ and [ReO2(DP-RGD)2]+ consist of a mixture of cis and trans geometric isomers. Finally, [99mTcO2(DP-RGD)2]+ exhibited high metabolic stability, and selectively targeted αvβ3-integrin receptors, enabling in vivo SPECT imaging of αvβ3-integrin receptor expression in mice.

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