Cyclam-Based Chelators Bearing Phosphonated Pyridine Pendants for Cu-PET Imaging: Synthesis, Physicochemical Studies, Radiolabeling, and Bioimaging.
Fiche publication
Date publication
janvier 2021
Journal
Inorganic chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHARBONNIERE Loïc, Dr ELHABIRI Mourad
Tous les auteurs :
Knighton RC, Troadec T, Mazan V, Le Saëc P, Marionneau-Lambot S, Le Bihan T, Saffon-Merceron N, Le Bris N, Chérel M, Faivre-Chauvet A, Elhabiri M, Charbonnière LJ, Tripier R
Lien Pubmed
Résumé
Herein we present the preparation of two novel cyclam-based macrocycles ( and ), bearing phosphonate-appended pyridine side arms for the coordination of copper(II) ions in the context of Cu PET imaging. The two ligands have been prepared through conventional protection-alkylation sequences on cyclam, and their coordination properties have been thoroughly investigated. The corresponding copper complexes have been fully characterized in the solid state (X-ray diffraction analysis) and in solution (EPR and UV-vis spectroscopies). Potentiometric studies combined with spectrometry have also allowed us to determine their thermodynamic stability constants, confirming their high affinity for copper(II) cations. The kinetic inertness of the complexes has been verified by acid-assisted dissociation experiments, enabling their use in Cu-PET imaging in mice for the first time. Indeed, the two ligands could be quantitatively radiolabeled under mild conditions, and the resulting Cu complexes have demonstrated excellent stability in serum. PET imaging demonstrated a set of features emerging from the combination of picolinates and phosphonate units: high stability , fast clearance from the body via renal elimination, and most interestingly, very low fixation in the liver. This is in contrast with what was observed for monopicolinate cyclam (), which had a non-negligible accumulation in the liver, owing probably to its different charge and lipophilicity. These results thus pave the way for the use of such phosphonated pyridine chelators for Cu-PET imaging.
Référence
Inorg Chem. 2021 Jan 26;: