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

被引：15
作者：
Andersen, Valdemar L. [1 ,2 ,3 ]
Hansen, Hanne D. [1 ,2 ]
Herth, Matthias M. [1 ,2 ]
Knudsen, Gitte M. [1 ,2 ]
Kristensen, Jesper L. [1 ,2 ,3 ]
机构：
[1] Rigshosp, CIMBI, DK-2100 Copenhagen, Denmark
[2] Univ Copenhagen, DK-2100 Copenhagen, Denmark
[3] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, DK-2100 Copenhagen, Denmark
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 11期
关键词：
Cross-coupling; Vortioxetine; PET; Carbon-11; Palladium; POSITRON-EMISSION-TOMOGRAPHY; SEROTONIN TRANSPORTER; 5-HT3; RECEPTOR; HUMAN BRAIN; LU AA21004; ANTIDEPRESSANTS; LOCALIZATION; DEPRESSION; BINDING; METHYL;
D O I：
10.1016/j.bmcl.2014.04.044
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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 C-11-labeling of vortioxetine with [C-11] MeI using a Suzuki-protocol that allows for the presence of an unprotected amine. Preliminary evaluation of [C-11] 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. [C-11] 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. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2408 / 2411
页数：4
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