Labeling and preliminary in vivo evaluation of the 5-HT7 receptor selective agonist [11C]E-55888

被引：11

作者：

Hansen, Hanne D. ^{[1
,2
]}

Andersen, Valdemar L. ^{[1
,2
,3
]}

Lehel, Szabolcs ^{[2
,4
]}

Magnussen, Janus H. ^{[1
,2
]}

Dyssegaard, Agnete ^{[1
,2
]}

Stroth, Nikolas ^{[5
,6
]}

Kristensen, Jesper L. ^{[3
]}

Knudsen, Gitte M. ^{[1
,2
]}

Herth, Matthias M. ^{[1
,2
,3
]}

机构：

[1] Rigshosp, Ctr Integrated Mol Brain Imaging, 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

[4] Rigshosp, PET & Cyclotron Unit, DK-2100 Copenhagen, Denmark

[5] Karolinska Inst, Dept Neurol & Clin Neurosci, Ctr Mol Med, S-17176 Stockholm, Sweden

[6] Karolinska Univ Hosp, S-17176 Stockholm, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 09期

关键词：

E-55888; PET; Carbon-11; 5-HT7; receptor; Agonist; RADIOLIGANDS; DESIGN;

D O I：

10.1016/j.bmcl.2015.03.039

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

E-55888 has been identified as a selective serotonin 7 (5-HT7) receptor agonist. In this study, we describe the synthesis, radiolabeling and in vivo evaluation of [C-11]E-55888 as a radioligand for positron emission tomography (PET) imaging. [C-11]E-55888 was obtained by N-methylation of an appropriate precursor using [C-11]MeOTf in acetone at 60 degrees C giving isolated quantities in the range of 1.7-2.4 GBq. Studies in Danish Landrace pigs demonstrated that [C-11]E-55888 has good brain uptake, however, the distribution in the brain tissue was dominated by non-specific binding, as binding could neither be displaced by the structurally different 5-HT7 receptor ligand SB-269970 nor by self-block with unlabeled E-55888. Based on these data, [C-11]E-55888 does not show promise as a PET radioligand for imaging the 5-HT7 receptor in vivo. (C) 2015 Elsevier Ltd. All rights reserved.

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页码：1901 / 1904

页数：4

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