Details

Autor(en) / Beteiligte

• Roux, Amandine
• Gillet, Raphaël
• Huclier-Markai, Sandrine
• Ehret-Sabatier, Laurence
• Charbonnière, Loïc J
• Nonat, Aline M

Titel

Bifunctional bispidine derivatives for copper-64 labelling and positron emission tomographyElectronic supplementary information (ESI) available. See DOI: 10.1039/c6ob02712a

Erscheinungsjahr

2017-02

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The first radiolabelling studies of a bispidine (3,7-diazabicyclo[3.3.1]nonane) derivative substituted by a glycinate pendant arm ( L 1 ) with 64 Cu are reported. Labelling was fast and easily performed at room temperature and in a wide range of pH values. Under these conditions, radiochemical yields over 90% were achieved within 5 minutes at micromolar concentration of the ligand. A bifunctional analogue of L 1 ( L 2 ) has been obtained by introducing an l -lysine amino acid on the bispidine skeleton. Ligand L 2 demonstrates good radiolabelling capacities at room temperature and in water (pH 4 to pH 6). This new bispidine is a versatile platform which can easily react with NHS esters and can be subsequently coupled to a recognition unit in order to perform targeted Positron Emission Tomography (PET) imaging. As a proof of concept, two new bifunctional chelators (BFCs) with a biotin ( L 3 ) or a maleimide functional group ( L 4 ) have been synthesized. The biotinylated BFC is very valuable for pretargeting strategies using streptavidin-conjugated antibodies. The reactivity of the maleimide derivative L 4 has been studied with the model peptide GP120. Quantitative coupling has been achieved under physiological conditions, showing a good regioselectivity towards cysteine residues versus lysine amino acids. A bispidine cage coordinates 64 Cu 2+ rapidly and quantitatively at room temperature, and biotin and maleimide functions allow for targeted PET imaging.