【摘要】 研发多巴胺D4受体显像剂,采用"一锅两步法"制备了一种潜在的多巴胺D4受体PET显像剂3-(4-[18F]氟苄基)-8,9-二甲氧-基1,2,3,4-四氢苯并吡喃[3,4-c]吡啶-5-酮(18F-FDTP),并用高效液相色谱法进行了分离纯化。其合成时间为105 min,放射化学产率为19.8%(衰变校正),纯化后放射化学纯度大于97%,比活度大于6.3×104PBq/mol。通过体外受体竞争结合分析,测定FDTP对多巴胺D4受体的亲和常数为8.1 nmol/L,对D2,D3受体的亲和常数分别大于5800,3000 nmol/L;通过分配实验,测得其脂水分配系数为0.85。初步的体外研究显示,18F-FDTP有希望用于D4受体显像,但还需经进一步试验证实。更多还原

【Abstract】 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-[18F]fluorobenzyl)-8,9-dimethoxy-1,2,3,4-tetrahydrochromeno[3,4-c] pyridin-5-one(18F-FDTP) was reportedly prepared from 18F-through a two-step one-pot method.Fluorine-18 was introduced to trimethylammoniumbenzaldehyde 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-tetrahydrochromeno[3,4-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 Ki of FDTP for D4.2 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 Ki 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.更多还原