Radiosynthesis of N-[4-(4-fluorobenzyl)piperidin-1-yl]-N '-(2-[C-11]oxo-1,3-dihydrobenzimidazol-5-yl)oxamide, a NR2B-selective NMDA receptor antagonist

In order to perform in vivo imaging of the NR2B NMDA receptor system by positron emission tomography, a NR2B selective NMDA receptor antagonist has been labelled with carbon-11 (half-life: 20min). N-[4-(4-fluorobenzyl)piperidin-1-yl]-N'-(2-oxo-1,3-dihydrobenzimidazol-5-yl)oxamide has been described demonstrating high affinity and selectivity for the NR2B receptors (IC50 of 5nM in [H-3]Ro-25,6981 binding assay). The labelling precursor and the reference compound were synthesized by coupling the 4-(4-fluorobenzyl)piperidine with the corresponding oxalamic acid. The reaction of [C-11]phosgene with phenylenediamine precursor led the formation of the [C-11]benzimidazolone ring present on the ligand. The labelling occurred in THF or acetonitrile and the decay corrected radiochemical yield was 30-40% from the produced [C-11]methane. HPLC purification and formulation led to 2.6-3.7 GBq (70-100mCi) of radioligand within 30-35 min. The specific radioactivity was 72-127 GBq/mu mol (2-3.4 Ci/mu mol) at the end of synthesis.