Synthesis, radiosynthesis and preliminary in vivo evaluation of [~(123)I]-(4-fluorophenyl) {l-[2-(2-iodophenyl)ethyl]piperidin-4-yl}methanone, a potential 5-HT_2A-antagonist for SPECT brain imaging

摘要

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-fruorophenyl) {l-[2-(2-iodopheny-l)ethyl]piperidin-4-yl}methanone, the synthesis of its precursor, (4-fluorophenyl) {l-[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/(mu)mol. 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.