Synthesis and preliminary evaluation of a carbon-11-labelled agonist of the alpha 7 nicotinic acetylcholine receptor

The lead compound of a new series of azabicyclic carbamates described by As tra Laboratories as ligands for the alpha7 nicotinic acetylcholine receptor subtype, namely N-(4-bromophenyl)carbamic acid quinuclidin-3-yl ester, has been labelled with carbon-11 using no-carrier-added [C-11]phosgene and the isocyanate pathway. Typically, 25-35 mCi (0.92-1.29 GBq) of the tracer was obtained within 30 min of radiosynthesis (HPLC purification included) with specific radioactivities ranging from 500 to 800 mCi/mu mol (18.5-29.6 GBq /mu mol). Biodistribution studies demonstrated a relatively good brain upta ke of the compound (0.8-1.2% I.D./g tissue in various brain regions), but w ithout preferential concentration in brain regions rich in alpha7-subtype n icotinic receptor (e.g. hippocampus, pons and colliculi). No specific bindi ng could be demonstrated in pre-saturation studies performed with both the cold compound and nicotine. Therefore, this ligand is not suitable for furt her exploration in PET imaging. Copyright (C) 2001 John Wiley & Sons, Ltd.