Stereoselective binding of 11 C‐labelled piquindone (Ro 22–1319) to dopamine‐D2 receptors in the living human brain

The stereoenantiomers of piquindone (Ro 22–1319), a new antipsychotic pyrroloisoquinoline derivative, were labelled with the positron‐emitting isotope 11 C. Only the (−)‐enantiomer inherits most of the biological activity of racemic piquindone. The compounds were examined by positron emission tomography (PET) for dopamine‐D2 receptor binding in the living brain of Cynomolgus monkeys and healthy human subjects. After i.v. administration of tracer doses the (−)‐enantiomer but not the (+)‐enantiomer was shown to accumulate markedly in the dopamine‐D2 receptor rich caudate/putamen in both species. After (−) 11 C piquindone injection, radioactivity in the human caudate/putamen, and the putamen/cerebellar activity ratio increased to about 2 during the hour when radioactivity could be followed. (−) 11 C piquindone binding in the monkey putamen was not easily displaceable by haloperidol. The results demonstrate that (−) but not (+)‐ 11 C piquindone has a high affinity for dopamine‐D2 receptors in the living human brain. The results are compatible with the view that clinical administration of piquindone produces a long‐lasting effect on central dopamine‐D2 receptors. (−) 11 C Piquindone is a useful ligand for visualization of dopamine‐D2 receptor binding by PET and for analysing relationships between antipsychotic effects of piquindone and blockade of specific binding sites in the brain of schizophrenic patients.