Radiochemical Synthesis and Receptor Binding Assay of ¹⁸F-FDTP as a Putative Dopamine D₄ Receptor Imaging Agent

Imaging of dopamine D₄ receptor with specific radioligand has been of increasing interest in recent years. Herein, a putative dopamine D₄ receptor tracer, 3-(4-¹⁸Ffluorobenzyl)-8, 9-dimethoxy-1, 2, 3, 4-tetrahydrochromeno3, 4-c pyridin-5-one (¹⁸F-FDTP) was reportedly prepared from ¹⁸F^- through a two-step one-pot method. Fluorine-18 was introduced to trimethylammoniumbenzaldehyde triflate by a nucleophilic halogen displacement on it. The fluorine-18 labeled intermediate was then reductively aminated with 8, 9-dimethoxy-1, 2, 3, 4-tetrahydrochromeno3, 4-c pyridine-5-one to form the target molecule. The radiochemical synthesis of ¹⁸F-FDTP take about 105 min with a total radiochemical yield of 19.8% (decaycorrected). Its radiochemical purity is greater than 97% after purification via HPLC and its specific activity is greater than 6.3×10⁴ PBq/mol. Through in vitroreceptor binding assay, the K_i of FDTP for D_4.2 receptor is determined to be 8.1 nmol/L, and for D₃, D₂ to be greater than 3 000, 5 800 nmol/L, respectively. The receptor binding experimental results exposed that FDTP demonstrated nanomolar K_i value for binding to the D₄ receptor with several hundredfold selectivities towards dopamine D₂ and D₃ receptors. The lipophilicity of it is determined to be 0.85. In conclusion, ¹⁸F-FDTP is radiochemically synthesized and its preliminary in vitrostudies indicate that ¹⁸F-FDTP shows promise as a potential imaging agent for dopamine D₄ receptor and further studies, such as in vivodistribution and PET imaging studies, are needed to evaluate the new tracer. 