Optimization and tissue distribution of [125I]iododomperidone as a radiotracer for D2-receptor imaging

Abstract

The aim of the present study is to use [125I]iododomperidone (125I-DOM) as a novel radioligand for dopamine D2-receptor (D2R) imaging. Therefore, a 12 h in vitro stable [125I]iododomperidone was synthesized with a maximum radiochemical yield (RCY) of 95.5% in subsistence of chloramine-T (CAT) as an oxidant. Furthermore, molecular operating environment (MOE) design was employed to assess the determination of the [125I]iododomperidone structure. The product structure was confirmed by employing cold iodination reaction using iodine-127. Moreover, the computational data which obtained from PreADMET software proved the increase of lipophilicity of [125I]iododomperidone over that of unlabeled one. In a trial to confirm the targeting ability of [125I]iododomperidone to D2R, docking study was performed and showed a successful binding of the labeled compound to the receptor. The biodistribution profile of [125I]iododomperidone in normal mice showed a rapid and high uptake of the brain (5.6 ± 0.2% ID/g organ) at 5 min post injection (p.i.). Consequently, [125I]iododomperidone will be a potential unprecedented D2R imaging agent for diagnosis of various neuropsychiatric disorders.