title: (211)At-labeled agents for alpha-immunotherapy: On the in vivo stability of astatine-agent bonds.
abstract: The application of (211)At to targeted cancer therapy is currently hindered by the rapid deastatination that occurs in vivo. As the deastatination mechanism is unknown, we tackled this issue from the viewpoint of the intrinsic properties of At-involving chemical bonds. An apparent correlation has been evidenced between in vivo stability of (211)At-labeled compounds and the At-R (R = C, B) bond enthalpies obtained from relativistic quantum mechanical calculations. Furthermore, we highlight important differences in the nature of the At-C and At-B bonds of interest, e.g. the opposite signs of the effective astatine charges, which implies different stabilities with respect to the biological medium. Beyond their practical use for rationalizing the labeling protocols used for (211)At, the proposed computational approach can readily be used to investigate bioactive molecules labeled with other heavy radionuclides.
authors.affiliation: CEISAM, CNRS UMR 6230, Université de Nantes, 2 Rue de la Houssinière, BP 92208, F-44322 Nantes Cedex 3, France.
authors.forename: Tahra
authors.initials: T
authors.lastname: Ayed
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, UMR 7616, Laboratoire de Chimie Théorique, F-75005 Paris, France; CNRS UMR 7616, Laboratoire de Chimie Théorique, F-75005 Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Pilmé
authors.affiliation: CEISAM, CNRS UMR 6230, Université de Nantes, 2 Rue de la Houssinière, BP 92208, F-44322 Nantes Cedex 3, France; SUBATECH, CNRS UMR 6457, IN2P3/EMN Nantes/Université de Nantes, 4 rue A. Kastler, F-44307 Nantes Cedex 3, France.
authors.forename: David
authors.initials: D
authors.lastname: Tézé
authors.affiliation: CEISAM, CNRS UMR 6230, Université de Nantes, 2 Rue de la Houssinière, BP 92208, F-44322 Nantes Cedex 3, France.
authors.forename: Fadel
authors.initials: F
authors.lastname: Bassal
authors.affiliation: GIP ARRONAX, 1 rue Aronnax, F-44817 Saint Herblain, France; Centre de Recherche en Cancérologie de Nantes-Angers, Inserm U892, CNRS UMR 6299, Université de Nantes, Institut de Recherche en Santé de l'Université de Nantes, 8 quai Moncousu, F-44007 Nantes Cedex 1, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Barbet
authors.affiliation: Centre de Recherche en Cancérologie de Nantes-Angers, Inserm U892, CNRS UMR 6299, Université de Nantes, Institut de Recherche en Santé de l'Université de Nantes, 8 quai Moncousu, F-44007 Nantes Cedex 1, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Chérel
authors.affiliation: SUBATECH, CNRS UMR 6457, IN2P3/EMN Nantes/Université de Nantes, 4 rue A. Kastler, F-44307 Nantes Cedex 3, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Champion
authors.affiliation: SUBATECH, CNRS UMR 6457, IN2P3/EMN Nantes/Université de Nantes, 4 rue A. Kastler, F-44307 Nantes Cedex 3, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Maurice
authors.affiliation: SUBATECH, CNRS UMR 6457, IN2P3/EMN Nantes/Université de Nantes, 4 rue A. Kastler, F-44307 Nantes Cedex 3, France. Electronic address: montavon@subatech.in2p3.fr.
authors.forename: Gilles
authors.initials: G
authors.lastname: Montavon
authors.affiliation: CEISAM, CNRS UMR 6230, Université de Nantes, 2 Rue de la Houssinière, BP 92208, F-44322 Nantes Cedex 3, France. Electronic address: nicolas.galland@univ-nantes.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Galland
mesh_terms: D001246:Astatine / Q000737:chemistry* / Q000627:therapeutic use*; D004355:Drug Stability; D007167:Immunotherapy / Q000379:methods*; D007553:Isotope Labeling; D008958:Models, Molecular; D008968:Molecular Conformation
chemical_list: D001246:Astatine
keywords: Astatine; Bond enthalpy; Density functional theory; In vivo stability; Targeted radionuclide therapy