Convergent [18]F-labeling and evaluation of N-benzyl-phenethylamines as 5-HT2A receptor PET ligands

Ida Nymann Petersen; Jonas Villadsen; Hanne Demant Hansen; Anders A Jensen; Szabolcs Lehel; Nic Gillings; Matthias M Herth; Gitte M Knudsen; Jesper L Kristensen

doi:10.1016/j.bmc.2016.08.056

Convergent [18]F-labeling and evaluation of N-benzyl-phenethylamines as 5-HT2A receptor PET ligands

Ida Nymann Petersen, Jonas Villadsen, Hanne Demant Hansen, Anders A Jensen, Szabolcs Lehel, Nic Gillings, Matthias M Herth, Gitte M Knudsen, Jesper L Kristensen

11 Citationer (Scopus)

Abstract

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 (11)C-labeled agonist PET ligand ([(11)C]Cimbi-36), and the aim of this study was to identify a (18)F-labeled analogue of this PET-ligand. Thus, we developed a convergent radiochemical approach giving easy access to 5 different (18)F-labeled ligands structurally related to Cimbi-36 from a common (18)F-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.

Originalsprog	Engelsk
Tidsskrift	Bioorganic & Medicinal Chemistry
Vol/bind	24
Sider (fra-til)	5353-5356
Antal sider	4
ISSN	0968-0896
DOI	https://doi.org/10.1016/j.bmc.2016.08.056
Status	Udgivet - 2016

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10.1016/j.bmc.2016.08.056

Citationsformater

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title = "Convergent [18]F-labeling and evaluation of N-benzyl-phenethylamines as 5-HT2A receptor PET ligands",

abstract = "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 (11)C-labeled agonist PET ligand ([(11)C]Cimbi-36), and the aim of this study was to identify a (18)F-labeled analogue of this PET-ligand. Thus, we developed a convergent radiochemical approach giving easy access to 5 different (18)F-labeled ligands structurally related to Cimbi-36 from a common (18)F-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.",

author = "Petersen, {Ida Nymann} and Jonas Villadsen and Hansen, {Hanne Demant} and Jensen, {Anders A} and Szabolcs Lehel and Nic Gillings and Herth, {Matthias M} and Knudsen, {Gitte M} and Kristensen, {Jesper L}",

year = "2016",

doi = "10.1016/j.bmc.2016.08.056",

language = "English",

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T1 - Convergent [18]F-labeling and evaluation of N-benzyl-phenethylamines as 5-HT2A receptor PET ligands

AU - Petersen, Ida Nymann

AU - Villadsen, Jonas

AU - Hansen, Hanne Demant

AU - Jensen, Anders A

AU - Lehel, Szabolcs

AU - Gillings, Nic

AU - Herth, Matthias M

AU - Knudsen, Gitte M

AU - Kristensen, Jesper L

PY - 2016

Y1 - 2016

N2 - 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 (11)C-labeled agonist PET ligand ([(11)C]Cimbi-36), and the aim of this study was to identify a (18)F-labeled analogue of this PET-ligand. Thus, we developed a convergent radiochemical approach giving easy access to 5 different (18)F-labeled ligands structurally related to Cimbi-36 from a common (18)F-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.

AB - 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 (11)C-labeled agonist PET ligand ([(11)C]Cimbi-36), and the aim of this study was to identify a (18)F-labeled analogue of this PET-ligand. Thus, we developed a convergent radiochemical approach giving easy access to 5 different (18)F-labeled ligands structurally related to Cimbi-36 from a common (18)F-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.

U2 - 10.1016/j.bmc.2016.08.056

DO - 10.1016/j.bmc.2016.08.056

M3 - Journal article

C2 - 27624522

SN - 0968-0896

VL - 24

SP - 5353

EP - 5356

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

ER -

Convergent [18]F-labeling and evaluation of N-benzyl-phenethylamines as 5-HT2A receptor PET ligands

Abstract

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