Synthesis of [123I]-3-(4-iodobenzyl)-1,2,3,4-tetrahydro-8-hydroxychromeno[3,4-c]pyridin-5-one, a potential dopamine D4 ligand for SPECT studies

Schizophrenia is a devastating mental disorder characterized by relapsing psychotic episodes accompanied with emotional, professional and social decline. The classical dopamine hypothesis of schizophrenia postulates that hyperactivity of dopaminergic neurotransmission is responsible for the positive symptoms of the disorder, more exactly hyperactivity of the dopamine D2-like receptors. One of these receptors is the D4 receptor which is thought to be involved in the motor side-effects caused antipsychotics. However, research into the specific role of this receptor has been hampered by the lack of specific ligands. Therefore, a new 123I-labelled compound was developed which may allow in vivo visualization of the D4 receptor by SPECT. [123I]-3-(4-iodobenzyl)-1,2,3,4-tetrahydro-8-hydroxychromeno[3,4-c]pyridin-5-one was prepared by electrophillic aromatic substitution of the tributylstannyl derivative. The radiochemical yield was 68±3% (n=5) and the specific activity was >2.96 Ci/µmol. Copyright © 2005 John Wiley & Sons, Ltd.