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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

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.

OriginalsprogEngelsk
TidsskriftBioorganic & Medicinal Chemistry Letters
Vol/bind25
Udgave nummer5
Sider (fra-til)1053–1056
Antal sider14
ISSN0960-894X
DOI
StatusUdgivet - 20 jan. 2015

ID: 131104161