(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.

journal_name

Bioorg Med Chem Lett

authors

Andersen VL,Hansen HD,Herth MM,Dyssegaard A,Knudsen GM,Kristensen JL

doi

10.1016/j.bmcl.2015.01.017

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

1053-6

issue

5

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(15)00029-3

journal_volume

25

pub_type

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