(11)C-labeling and preliminary evaluation of vortioxetine as a PET radioligand

Valdemar L Andersen; Hanne D Hansen; Matthias M Herth; Gitte M Knudsen; Jesper L Kristensen

doi:10.1016/j.bmcl.2014.04.044

(11)C-labeling and preliminary evaluation of vortioxetine as a PET radioligand

Bioorg Med Chem Lett. 2014 Jun 1;24(11):2408-11. doi: 10.1016/j.bmcl.2014.04.044. Epub 2014 Apr 19.

Authors

Valdemar L Andersen¹, Hanne D Hansen², Matthias M Herth², Gitte M Knudsen², Jesper L Kristensen³

Affiliations

¹ Center for Integrated Molecular Brain Imaging (CIMBI), Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
² Center for Integrated Molecular Brain Imaging (CIMBI), Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
³ Center for Integrated Molecular Brain Imaging (CIMBI), Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. Electronic address: [email protected].

PMID: 24786133
DOI: 10.1016/j.bmcl.2014.04.044

Abstract

Vortioxetine is a new multi-modal drug against major depressive disorder with high affinity for a range of different serotonergic targets in the CNS. We report the (11)C-labeling of vortioxetine with [(11)C]MeI using a Suzuki-protocol that allows for the presence of an unprotected amine. Preliminary evaluation of [(11)C]vortioxetine in a Danish Landrace pig showed rapid brain uptake and brain distribution in accordance with the pharmacological profile, all though an unexpected high binding in cerebellum was also observed. [(11)C]vortioxetine displayed slow tracer kinetics with peak uptake after 60 min and with limited wash-out from the brain. Further studies are needed but this radioligand may prove to be a valuable tool in unraveling the clinical effects of vortioxetine.

Keywords: Carbon-11; Cross-coupling; PET; Palladium; Vortioxetine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / metabolism
Carbon Radioisotopes
Isotope Labeling
Ligands
Piperazines* / chemistry
Piperazines* / pharmacokinetics
Positron-Emission Tomography / methods*
Radiopharmaceuticals
Sulfides* / chemistry
Sulfides* / pharmacokinetics
Swine
Tissue Distribution
Vortioxetine

Substances

Carbon Radioisotopes
Ligands
Piperazines
Radiopharmaceuticals
Sulfides
Vortioxetine