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

页码：2408 / 2411

页数：4