Synthesis, radiosynthesis and preliminary in vivo evaluation of [ 123 I]‐(4‐fluorophenyl) {1‐[2‐(2‐iodophenyl)ethyl]piperidin‐4‐yl}methanone, a potential 5‐HT 2A ‐antagonist for SPECT brain imaging

Many people suffer from psychiatric illnesses like depression and anorexia. Relevant to these diseases is amongst others a malfunctioning of brain 5‐HT 2A ‐receptors. To allow in vivo quantification of these receptors with Single Photon Emission Computerized Tomography (SPECT), a radiolabelled ligand with high 5‐HT 2A affinity is needed. This work reports the radiosynthesis of [ 123 I]‐(4‐fluorophenyl) {1‐[2‐(2‐iodophenyl)ethyl]piperidin‐4‐yl}methanone, the synthesis of its precursor, (4‐fluorophenyl) {1‐[2‐(2‐bromophenyl)ethyl]piperidin‐4‐yl}methanone, and the preliminary in vivo evaluation of the tracer. The precursor was synthesized with a total yield of 40%. Radiolabelling was performed using a halogen exchange reaction and the yield was 70%. Radiochemical purity was >95%, and specific activity was at least 2.4 Ci/µmol. Log P was measured to be 2.52. The tracer showed uptake in mice brain (3.5% I.D./g tissue at 3 min post injection) and therefore will be evaluated further by regional brain biodistribution and displacement studies in rabbits. Copyright © 2004 John Wiley & Sons, Ltd.