(11)C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand

Valdemar L Andersen; Hanne D Hansen; Matthias M Herth; Agnete Dyssegaard; Gitte M Knudsen; Jesper Langgaard Kristensen

doi:10.1016/j.bmcl.2015.01.017

(11)C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand

Valdemar L Andersen, Hanne D Hansen, Matthias M Herth, Agnete Dyssegaard, Gitte M Knudsen, Jesper Langgaard Kristensen

8 Citations (Scopus)

Abstract

Pimavanserin is a selective serotonin 2A receptor (5-HT2AR) inverse agonist that has shown promise for treatment of psychotic symptoms in patients with Parkinson's disease. Here, we detail the (11)C-labeling and subsequently evaluate pimavanserin as a PET-radioligand in pigs. [(11)C]Pimavanserin was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60°C giving radiochemical yields in the range of 1-1.7GBq (n=4). In Danish Landrace pigs the radio ligand readily entered the brain and displayed binding in the cortex in accordance with the distribution of 5-HT2ARs. However, this binding could not be blocked by either ketanserin or pimavanserin itself, indicating high nonspecific binding. The lack of displacement by the 5-HT2R antagonist and binding in the thalamus suggests that [(11)C]pimavanserin is not selective for the 5-HT2AR in pigs.

Original language	English
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	25
Issue number	5
Pages (from-to)	1053–1056
Number of pages	14
ISSN	0960-894X
DOIs	https://doi.org/10.1016/j.bmcl.2015.01.017
Publication status	Published - 1 Mar 2015

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title = "(11)C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand",

abstract = "Pimavanserin is a selective serotonin 2A receptor (5-HT2AR) inverse agonist that has shown promise for treatment of psychotic symptoms in patients with Parkinson's disease. Here, we detail the (11)C-labeling and subsequently evaluate pimavanserin as a PET-radioligand in pigs. [(11)C]Pimavanserin was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60°C giving radiochemical yields in the range of 1-1.7GBq (n=4). In Danish Landrace pigs the radio ligand readily entered the brain and displayed binding in the cortex in accordance with the distribution of 5-HT2ARs. However, this binding could not be blocked by either ketanserin or pimavanserin itself, indicating high nonspecific binding. The lack of displacement by the 5-HT2R antagonist and binding in the thalamus suggests that [(11)C]pimavanserin is not selective for the 5-HT2AR in pigs.",

author = "Andersen, {Valdemar L} and Hansen, {Hanne D} and Herth, {Matthias M} and Agnete Dyssegaard and Knudsen, {Gitte M} and Kristensen, {Jesper Langgaard}",

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T1 - (11)C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand

AU - Andersen, Valdemar L

AU - Hansen, Hanne D

AU - Herth, Matthias M

AU - Dyssegaard, Agnete

AU - Knudsen, Gitte M

AU - Kristensen, Jesper Langgaard

PY - 2015/3/1

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N2 - Pimavanserin is a selective serotonin 2A receptor (5-HT2AR) inverse agonist that has shown promise for treatment of psychotic symptoms in patients with Parkinson's disease. Here, we detail the (11)C-labeling and subsequently evaluate pimavanserin as a PET-radioligand in pigs. [(11)C]Pimavanserin was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60°C giving radiochemical yields in the range of 1-1.7GBq (n=4). In Danish Landrace pigs the radio ligand readily entered the brain and displayed binding in the cortex in accordance with the distribution of 5-HT2ARs. However, this binding could not be blocked by either ketanserin or pimavanserin itself, indicating high nonspecific binding. The lack of displacement by the 5-HT2R antagonist and binding in the thalamus suggests that [(11)C]pimavanserin is not selective for the 5-HT2AR in pigs.

AB - Pimavanserin is a selective serotonin 2A receptor (5-HT2AR) inverse agonist that has shown promise for treatment of psychotic symptoms in patients with Parkinson's disease. Here, we detail the (11)C-labeling and subsequently evaluate pimavanserin as a PET-radioligand in pigs. [(11)C]Pimavanserin was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60°C giving radiochemical yields in the range of 1-1.7GBq (n=4). In Danish Landrace pigs the radio ligand readily entered the brain and displayed binding in the cortex in accordance with the distribution of 5-HT2ARs. However, this binding could not be blocked by either ketanserin or pimavanserin itself, indicating high nonspecific binding. The lack of displacement by the 5-HT2R antagonist and binding in the thalamus suggests that [(11)C]pimavanserin is not selective for the 5-HT2AR in pigs.

U2 - 10.1016/j.bmcl.2015.01.017

DO - 10.1016/j.bmcl.2015.01.017

M3 - Journal article

C2 - 25655720

SN - 0960-894X

VL - 25

SP - 1053

EP - 1056

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 5

ER -

(11)C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand

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