Convergent 18F-labeling and evaluation of N-benzylphenethylamines as 5-HT2A receptor PET ligands

被引：10
作者：
Petersen, Ida Nymann [1 ]
Villadsen, Jonas [2 ,3 ]
Hansen, Hanne Demant [2 ,3 ]
Jensen, Anders A. [1 ]
Lehel, Szabolcs [4 ]
Gillings, Nic [4 ]
Herth, Matthias M. [1 ,4 ]
Knudsen, Gitte M. [2 ,3 ]
Kristensen, Jesper L. [1 ]
机构：
[1] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Univ Pk 2, DK-2100 Copenhagen O, Denmark
[2] Rigshosp, CIMBI, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
[3] Univ Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
[4] Rigshosp, Dept Clin Physiol Nucl Med & PET, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2016年 / 24卷 / 21期
关键词：
F-18-labeling; PET; Serotonin; 5-HT2A receptor agonist; EMISSION-TOMOGRAPHY; RADIOLIGAND; AGONISTS; RELEASE; DESIGN;
D O I：
10.1016/j.bmc.2016.08.056
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Positron emission tomography (PET) investigations of the 5-HT2A receptor (5-HT2AR) system can be used as a research tool in diseases such as depression, Alzheimer's disease and schizophrenia. We have previously developed a C-11-labeled agonist PET ligand ([C-11]Cimbi-36), and the aim of this study was to identify a F-18-labeled analogue of this PET-ligand. Thus, we developed a convergent radiochemical approach giving easy access to 5 different F-18-labeled ligands structurally related to Cimbi-36 from a common F-18-labeled intermediate. After intravenous injection, all ligands entered the pig brain. However, since within-scan intervention with ketanserin, a known orthosteric 5-HT2A receptor antagonist, did not result in significant blocking, the radioligands seem unsuitable for neuroimaging of the 5-HT2AR in vivo. (C) 2016 Elsevier Ltd. All rights reserved.
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收藏
页码：5353 / 5356
页数：4
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