Radiochemical labelling of the dopamine D-3 receptor ligand RGH-1756

The dopamine D-3 receptor is expressed in low density in limbic brain areas . The receptor subtype has been proposed as a target for novel antipsychoti c drugs, however no selective positron emission tomography (PET) ligand is to date available to study the receptor distribution in vivo. 1-(2-Methoxyp henyl)-4-{4-[4-(6-imidazo[2,1-b]-thiazolyl)phenoxy]butyl}piperazine (RGH-17 56) is a new methoxy-phenylpiperazine derivative that possesses high affini ty (K-i: 0.119 nM) and good selectivity for the human dopamine D-3 receptor . In an attempt to develop a PET radioligand for the visualisation of the d opamine D-3 receptor in human brain we synthesised carbon-11-labelled RGH-1 756. The radiolabelling was performed by reaction of the corresponding desm ethyl precursor 1-(2-hydroxyphenyl)-4-{4-[4-(6-imidazo[2,1-b]-thiazolyl)phe noxy]butyl}piperazine (04512626) with [C-11]methyl triflate in acetone and aqueous NaOH. The HPLC-determined incorporation yield was >90%. The total s ynthesis time was 35 min and the specific radioactivity at end of synthesis ranged from 66 to 132 GBq/mu mol.