Synthesis and evaluation of radioligands for imaging brain nociceptin/orphanin FQ peptide (NOP) receptors with positron emission tomography.

ABSTRACT: Positron emission tomography (PET) coupled to an effective radioligand could provide an important tool for understanding possible links between neuropsychiatric disorders and brain NOP (nociceptin/orphanin FQ peptide) receptors. We sought to develop such a PET radioligand. High-affinity NOP ligands were synthesized based on a 3-(2'-fluoro-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran]-1-yl)-2(2-halobenzyl)-N-alkylpropanamide scaffold and from experimental screens in rats, with ex vivo LC-MS/MS measures, three ligands were identified for labeling with carbon-11 and evaluation with PET in monkey. Each ligand was labeled by (11)C-methylation of an N-desmethyl precursor and studied in monkey under baseline and NOP receptor-preblock conditions. The three radioligands, [(11)C](S)-10a-c,

SUBMITTER: Pike VW 

PROVIDER: S-EPMC3081360 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature