Synthesis and biological evaluation of positron emission tomography radiotracers targeting serotonin 4 receptors in brain: [18F]MNI-698 and [18F]MNI-699

被引：17

作者：

Caille, Fabien

Morley, Thomas J.

Tavares, Adriana Alexandre S.

Papin, Caroline

Twardy, Nicole M.

Alagille, David

Lee, H. Sharon

Baldwin, Ronald M.

Seibyl, John P.

Barret, Olivier

Tamagnan, Gilles D. ^{[1
]}

机构：

[1] Mol NeuroImaging LLC, New Haven, CT 06510 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 23期

关键词：

PET imaging; 5-HT4; Serotonin receptors; Fluorine-18; Alzheimer's disease; POSTMORTEM HUMAN BRAIN; 5-HT4; RECEPTORS; GUINEA-PIG; IN-VIVO; SELECTIVE RADIOLIGAND; HIGHLY POTENT; BINDING; ANTAGONIST; SB-207710; LIGAND;

D O I：

10.1016/j.bmcl.2013.09.097

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Two new benzodioxane derivatives were synthesized as candidates to image the serotonin 4 receptors by positron emission tomography (PET) and radiolabeled with fluorine-18 via a two-step procedure. Competition binding assays demonstrated that MNI-698 and MNI-699 had sub-nanomolar binding affinities against rat striatal 5-HT4 receptors (Ki of 0.20 and 0.07 nM, respectively). PET imaging in rhesus monkey showed that the regional brain distribution of [F-18] MNI-698 and [F-18] MNI-699 were consistent with the known densities of 5-HT4 in brain. [F-18] MNI-698 and [F-18] MNI-699 are among the first fluorine-18 radiotracers developed for imaging the 5-HT4 receptors in vivo and are currently under preclinical investigation in primates for future human use. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：6243 / 6247

页数：5

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