title: Bifunctional bispidine derivatives for copper-64 labelling and positron emission tomography.
abstract: The first radiolabelling studies of a bispidine (3,7-diazabicyclo[3.3.1]nonane) derivative substituted by a glycinate pendant arm (L1) with64Cu 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 L1 (L2) has been obtained by introducing an l-lysine amino acid on the bispidine skeleton. Ligand L2 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 (L3) or a maleimide functional group (L4) have been synthesized. The biotinylated BFC is very valuable for pretargeting strategies using streptavidin-conjugated antibodies. The reactivity of the maleimide derivative L4 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.
authors.affiliation: Laboratoire d'Ingénierie Moléculaire Appliquée à l'Analyse, Université de Strasbourg, CNRS, IPHC UMR 7178, F-67000 Strasbourg, France. aline.nonat@unistra.fr l.charbonn@unistra.fr.
authors.forename: Amandine
authors.initials: A
authors.lastname: Roux
authors.affiliation: Laboratoire d'Ingénierie Moléculaire Appliquée à l'Analyse, Université de Strasbourg, CNRS, IPHC UMR 7178, F-67000 Strasbourg, France. aline.nonat@unistra.fr l.charbonn@unistra.fr.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Gillet
authors.affiliation: GIP Arronax, 1 rue Arronax, BP 10112, 44817 Saint-Herblain, France and Subatech Laboratory, UMR 6457, Ecole des Mines de Nantes, IN2P3/CNRS, Université de Nantes, 4 rue Alfred Kastler, 44300 Nantes, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Huclier-Markai
authors.affiliation: Laboratoire de Spectrométrie de Masse BioOrganique, Université de Strasbourg, CNRS, IPHC UMR 7178, F-67000 Strasbourg, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Ehret-Sabatier
authors.affiliation: Laboratoire d'Ingénierie Moléculaire Appliquée à l'Analyse, Université de Strasbourg, CNRS, IPHC UMR 7178, F-67000 Strasbourg, France. aline.nonat@unistra.fr l.charbonn@unistra.fr.
authors.forename: Loïc J
authors.initials: LJ
authors.lastname: Charbonnière
authors.affiliation: Laboratoire d'Ingénierie Moléculaire Appliquée à l'Analyse, Université de Strasbourg, CNRS, IPHC UMR 7178, F-67000 Strasbourg, France. aline.nonat@unistra.fr l.charbonn@unistra.fr.
authors.forename: Aline M
authors.identifier: http://orcid.org/0000-0003-0478-5039
authors.initials: AM
authors.lastname: Nonat