(11)C-labeling and preliminary evaluation of vortioxetine as a PET radioligand.
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.
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.
Valdemar L
VL
Andersen
Center for Integrated Molecular Brain Imaging (CIMBI), Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Hanne D
HD
Hansen
Center for Integrated Molecular Brain Imaging (CIMBI), Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Matthias M
MM
Herth
Center for Integrated Molecular Brain Imaging (CIMBI), Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Gitte M
GM
Knudsen
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: jesper.kristensen@sund.ku.dk.
Jesper L
JL
Kristensen
D000818:Animals; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes; D007553:Isotope Labeling; D008024:Ligands; D010879:Piperazines / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D013440:Sulfides / Q000737:chemistry / Q000493:pharmacokinetics; D013552:Swine; D014018:Tissue Distribution; D000078784:Vortioxetine
D002250:Carbon Radioisotopes; D008024:Ligands; D010879:Piperazines; D019275:Radiopharmaceuticals; D013440:Sulfides; D000078784:Vortioxetine
Carbon-11; Cross-coupling; PET; Palladium; Vortioxetine