Synthesis and biological evaluation of 18 F-labelled dopamine D 3 receptor selective ligands

The dopamine D receptor (D R) is highly expressed in the limbic regions of the brain and closely related to a variety of neurological disorders including Parkinson's disease, schizophrenia and drug-seeking behavior. In vivo imaging of D R with radio-labelled tracers and positron emission tomography (PET) has become a powerful technique in related disorders. In this study, we synthesized three novel aromatically F-labelled phenylpiperazine-like D R selective radioactive ligands ([ F]5b, [ F]8b and [ F]11b) and developed a simple, rapid and efficient F-labelling method by condition optimization. Radiosynthesis of [ F]5b, [ F]8b and [ F]11b was achieved by F-fluorination from nitroarene precursors. Final radiochemical purities of [ F]5b, [ F]8b and [ F]11b solution were > 99% and remained good stability (> 98% for up to 6 h) in PBS and FBS. PET imaging and cellular binding studies revealed that [ F]8b had a higher D R affinity than [ F]5b and [ F]11b. Autoradiography and biodistribution studies of the brain showed that [ F]8b had medium intensity specific accumulation in the striatum and cortex. Meanwhile, the low skeletal uptake of [ F]8b revealed a good in vivo stability with negligible defluorination. These results indicated that [ F]8b might be a potential F-labelled D R PET imaging agent.