多巴胺D4受体PET显像剂^18F—FDTP的生物学研究

目的测定潜在的多巴胺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（FDTP）在大鼠体内的生物分布和阻断分布及评价其用于多巴胺D4受体显像的可能性。方法将溶于乙醇-生理盐水的^18F—FDTP与小牛血清一起孵育，通过测定放化纯分析其体外稳定性；通过大鼠尾静脉注射^18F—FDTP后2，5，10，15，30，60和120min取血液、感兴趣的脏器和脑组织，测定质量和放射性计数，观察^18F—FDTP在大鼠体内的生物分布和阻断分布，用每克组织百分注射剂量率（％ID／g）表示。结果^18F—FDTP在小牛血清中稳定性较好，37℃孵育120min后放化纯仍保持在95％以上。^18F-FDTP能通过血脑屏障进入脑，并在纹状体、下丘脑、额叶皮质、海马、小脑等D4受体分布区域有较高的摄取率，注药2min后海马、下丘脑、纹状体、额叶皮质、小脑、脑桥的放射性分别达（0．42±0．03）、（0．46±0．05）、（0．54±0．04）、（0．39±0．04）、（0．45±0．06）、（0．35±0．04）％ID／g，但阻断分布分别为（0．36±0．05）、（0．33±0．05）、（0．55±0．05）、（0．30±0．07）、（0．34±0．07）、（0．32±0．04）％ID／g。结论^18F-FDTP能通过大鼠血脑屏障进入脑，但其可能对脑内除D4受体外的其他受体亦有一定亲和性。

Biological evaluation of ~(18)F-FDTP as a potential dopamine D_4 receptor PET imaging agent

Objective To evaluate the feasibility of 3-(4-~(18)F-fluorobenzyl)-8,9-dimethoxy-1,2,3,4-tetrahydrochromeno 3,4-c]pyridin-5-one ( is F-FDTP) as a potential dopamine D4 receptor PET imaging agent.Methods ~(18)F-FDTP solution in ethanol-physiological saline was incubated with calf serum to test its in vitro stability through the determination of radiochemical purity.Normal rats were injected intravenously with ~(18)F-FDTP and then sacrificed at 2,5,10,15,30,60 and 120 min after anesthesia.Blood,organs and brain tissue samples were collected.All samples were weighed and measured for radioactivity.The uptake of samples was expressed as percentage activity of injection dose per gram of tissue ( % ID/g).Results The stability of ~(18)F-FDTP was satisfactory and its radiochemical purity was above 95% after incubation 120 min at 37℃ in calf serum.The biodistribution showed that ~(18)F-FDTP could penetrate through the blood-brain barrier and selectively accumulate in striatum,hypothalamus,frontal certex,hippocampus,cerebellum,where the D_4 receptor was reportedly located.The radioactivities in hippocampus,hypothalamus,striatum,frontal cortex,cerebellum,pons were (0.42±0.03),(0.46±0.05),(0.54±0.04),(0.39±0.04),(0.45±0.06),(0.35±0.04) %ID/g,respectively,2 min post injection.And there was difference between the normal biodistribution results and the blocking experimental results:(0.36 ±0.05),( 0.33±0.05 ),(0.55±0.05 ),(0.30±0.07 ),(0.34±0.07 ) and (0.32±0.04) % ID/g in hippocampus,hypothalamus,striatum,frontal cortex,cerebellum and pons,respectively.Conclusions ~(18)F-FDTP can penetrate through the blood-brain barrier and selectively accumulate in striatum,hypothalamus,frontal cortex,hippocampus,cerebellum,where the D_4 receptor was known to concentrate.These preliminary results suggest that ~(18)F-FDTP is a potential dopamine D_4 receptor imaging agent and further studies are needed.