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One-step, kit-based radiopharmaceuticals for molecular SPECT imaging: a versatile diphosphine chelator for 99mTc radiolabelling of peptides.
- Source :
- Dalton Transactions: An International Journal of Inorganic Chemistry; 11/28/2021, Vol. 50 Issue 44, p16156-16165, 10p
- Publication Year :
- 2021
-
Abstract
- Radiotracers labelled with technetium-99m (<superscript>99m</superscript>Tc) enable accessible diagnostic imaging of disease, provided that radiotracer preparation is simple. Whilst <superscript>99m</superscript>Tc radiopharmaceuticals for imaging perfusion are routinely prepared from kits, and regularly used in healthcare, there are no <superscript>99m</superscript>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 <superscript>99m</superscript>Tc-labelled radiotracers: its conjugates are simple to prepare and can be easily labelled with <superscript>99m</superscript>Tc using one-step, kit-based protocols. Here, reaction of BMA with the α<subscript>v</subscript>β<subscript>3</subscript>-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 <superscript>99m</superscript>TcO<subscript>4</subscript><superscript>−</superscript> to this kit, followed by heating, furnished the radiotracer [<superscript>99m</superscript>TcO<subscript>2</subscript>(DP-RGD)<subscript>2</subscript>]<superscript>+</superscript> in consistently high radiochemical yields (>90%). The analogous [ReO<subscript>2</subscript>(DP-RGD)<subscript>2</subscript>]<superscript>+</superscript> compound was prepared and characterised, revealing that both [<superscript>99m</superscript>TcO<subscript>2</subscript>(DP-RGD)<subscript>2</subscript>]<superscript>+</superscript> and [ReO<subscript>2</subscript>(DP-RGD)<subscript>2</subscript>]<superscript>+</superscript> consist of a mixture of cis and trans geometric isomers. Finally, [<superscript>99m</superscript>TcO<subscript>2</subscript>(DP-RGD)<subscript>2</subscript>]<superscript>+</superscript> exhibited high metabolic stability, and selectively targeted α<subscript>v</subscript>β<subscript>3</subscript>-integrin receptors, enabling in vivo SPECT imaging of α<subscript>v</subscript>β<subscript>3</subscript>-integrin receptor expression in mice. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14779226
- Volume :
- 50
- Issue :
- 44
- Database :
- Complementary Index
- Journal :
- Dalton Transactions: An International Journal of Inorganic Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 153628620
- Full Text :
- https://doi.org/10.1039/d1dt03177e