| Autor: |
Hungnes IN; King's College London, School of Biomedical Engineering and Imaging Sciences, 4th Floor Lambeth Wing, St Thomas' Hospital, London, UK. michelle.ma@kcl.ac.uk., Al-Salemee F; King's College London, School of Biomedical Engineering and Imaging Sciences, 4th Floor Lambeth Wing, St Thomas' Hospital, London, UK. michelle.ma@kcl.ac.uk., Gawne PJ; King's College London, School of Biomedical Engineering and Imaging Sciences, 4th Floor Lambeth Wing, St Thomas' Hospital, London, UK. michelle.ma@kcl.ac.uk., Eykyn T; King's College London, School of Biomedical Engineering and Imaging Sciences, 4th Floor Lambeth Wing, St Thomas' Hospital, London, UK. michelle.ma@kcl.ac.uk., Atkinson RA; King's College London, Randall Centre for Cell and Molecular Biophysics, and Centre for Biomolecular Spectroscopy, London, UK.; Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, Université Paul Sabatier, 31077 Toulouse, France., Terry SYA; King's College London, School of Biomedical Engineering and Imaging Sciences, 4th Floor Lambeth Wing, St Thomas' Hospital, London, UK. michelle.ma@kcl.ac.uk., Clarke F; King's College London, Centre for Inflammation Biology and Cancer Immunology, Faculty of Life Sciences and Medicine, London, UK., Blower PJ; King's College London, School of Biomedical Engineering and Imaging Sciences, 4th Floor Lambeth Wing, St Thomas' Hospital, London, UK. michelle.ma@kcl.ac.uk., Pringle PG; University of Bristol, School of Chemistry, Cantock's Close, Bristol, UK., Ma MT; King's College London, School of Biomedical Engineering and Imaging Sciences, 4th Floor Lambeth Wing, St Thomas' Hospital, London, UK. michelle.ma@kcl.ac.uk. |
| Abstrakt: |
Radiotracers labelled with technetium-99m ( 99m Tc) enable accessible diagnostic imaging of disease, provided that radiotracer preparation is simple. Whilst 99m Tc radiopharmaceuticals for imaging perfusion are routinely prepared from kits, and regularly used in healthcare, there are no 99m Tc-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 99m Tc-labelled radiotracers: its conjugates are simple to prepare and can be easily labelled with 99m Tc using one-step, kit-based protocols. Here, reaction of BMA with the α v β 3 -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 99m TcO 4 - to this kit, followed by heating, furnished the radiotracer [ 99m TcO 2 (DP-RGD) 2 ] + in consistently high radiochemical yields (>90%). The analogous [ReO 2 (DP-RGD) 2 ] + compound was prepared and characterised, revealing that both [ 99m TcO 2 (DP-RGD) 2 ] + and [ReO 2 (DP-RGD) 2 ] + consist of a mixture of cis and trans geometric isomers. Finally, [ 99m TcO 2 (DP-RGD) 2 ] + exhibited high metabolic stability, and selectively targeted α v β 3 -integrin receptors, enabling in vivo SPECT imaging of α v β 3 -integrin receptor expression in mice. |
