Convergent 18F-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 ¹⁸F-labeling and evaluation of N-benzyl-phenethylamines as 5-HT_2A receptor PET ligands

Bioorg Med Chem. 2016 Nov 1;24(21):5353-5356. doi: 10.1016/j.bmc.2016.08.056. Epub 2016 Aug 29.

Authors

Ida Nymann Petersen¹, Jonas Villadsen², Hanne Demant Hansen², Anders A Jensen¹, Szabolcs Lehel³, Nic Gillings³, Matthias M Herth⁴, Gitte M Knudsen², Jesper L Kristensen⁵

Affiliations

¹ Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 København Ø, Denmark.
² Center for Integrated Molecular Brain Imaging (CIMBI), Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
³ Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
⁴ Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 København Ø, Denmark; Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
⁵ Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 København Ø, Denmark. Electronic address: [email protected].

PMID: 27624522
DOI: 10.1016/j.bmc.2016.08.056

Abstract

Positron emission tomography (PET) investigations of the 5-HT_2A receptor (5-HT_2AR) system can be used as a research tool in diseases such as depression, Alzheimer's disease and schizophrenia. We have previously developed a ¹¹C-labeled agonist PET ligand ([¹¹C]Cimbi-36), and the aim of this study was to identify a ¹⁸F-labeled analogue of this PET-ligand. Thus, we developed a convergent radiochemical approach giving easy access to 5 different ¹⁸F-labeled ligands structurally related to Cimbi-36 from a common ¹⁸F-labeled intermediate. After intravenous injection, all ligands entered the pig brain. However, since within-scan intervention with ketanserin, a known orthosteric 5-HT_2A receptor antagonist, did not result in significant blocking, the radioligands seem unsuitable for neuroimaging of the 5-HT_2AR in vivo.

Keywords: (18)F-labeling; 5-HT(2A) receptor agonist; PET; Serotonin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzyl Compounds / chemical synthesis
Benzyl Compounds / chemistry
Benzyl Compounds / pharmacology*
Dose-Response Relationship, Drug
Ethylamines / chemical synthesis
Ethylamines / chemistry
Ethylamines / pharmacology*
Fluorine Radioisotopes
Humans
Ligands
Molecular Structure
Positron-Emission Tomography*
Radiopharmaceuticals / chemical synthesis
Radiopharmaceuticals / chemistry
Radiopharmaceuticals / pharmacology*
Receptor, Serotonin, 5-HT2A / metabolism*
Serotonin 5-HT2 Receptor Agonists / chemical synthesis
Serotonin 5-HT2 Receptor Agonists / chemistry
Serotonin 5-HT2 Receptor Agonists / pharmacology*
Structure-Activity Relationship

Substances

Benzyl Compounds
Ethylamines
Fluorine Radioisotopes
Ligands
N-benzyl-phenethylamine
Radiopharmaceuticals
Receptor, Serotonin, 5-HT2A
Serotonin 5-HT2 Receptor Agonists