Fluorine-18-labelled NCQ 115, a selective dopamine D-2 receptor ligand. Preparation and positron emission tomography

Abstract

NCQ 115 (( + )-( R)-5-bromo- N-((1-(4-fluorobenzyl)-2-pyrrolidinyl)methyl)-2,3-dimethoxybenzamide) is a selective dopamine D-2 receptor antagonist. NCQ 115 has a fluorine in a synthetically suitable position in the parent compound and was therefore suggested as a potential 18F-labelled radioligand for positron emission tomography (PET). [ 18F]4-Fluorobenzyl iodide was prepared in a 3-step synthesis from [ 18F]fluoride. N-4-Fluorobenzylation of the corresponding secondary pyrrolidine precursor was performed in DMF followed by purification with semi-preparative HPLC. The total radiochemical yield (EOB and decay-corrected) was 15–20% with a total synthesis time of 90 min and a radiochemical purity >99%. The specific radioactivity at the end of synthesis (EOS) was about 1500 Ci/mmol (55.5 GBq/μmol). [ 18F]NCQ 115 was injected into a Cynomolgus monkey for PET examination of brain in vivo. There was a conspicuous uptake of radioactivity in the monkey striatum. A specific [ 18F]NCQ 115 binding reached a peak after about 60 min which indicates equilibrium.