CAJ | 학술논문

目的测定潜在的多巴胺D4受体PET显像剂3-(4-~(18)F-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D_4受体显像的可能性.方法将溶于乙醇-生理盐水的~(18)F-FD/TP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~(18)F-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~(18)F-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 ~(18)F-FDTP在小牛血清中稳定性较好,37℃孵育120 min后放化纯仍保持在95%以上.~(18)F-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2 min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 ~(18)F-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.
목적 측정잠재적다파알D4수체PET현상제3-(4-~(18)F-불변기)-8,9-이갑양기-1,2,3,4-사경분병필남[3,4-c]필정-5-동(FDTP)재대서체내적생물분포화조단분포급평개기용우다파알D_4수체현상적가능성.방법 장용우을순-생리염수적~(18)F-FD/TP여소우혈청일기부육,통과측정방화순분석기체외은정성;통과대서미정맥주사~(18)F-FDTP후2,5,10,15,30,60화120min취혈액、감흥취적장기화뇌조직,측정질량화방사성계수,관찰~(18)F-FDTP재대서체내적생물분포화조단분포,용매극조직백분주사제량솔(%ID/g)표시.결과 ~(18)F-FDTP재소우혈청중은정성교호,37℃부육120 min후방화순잉보지재95%이상.~(18)F-FDTP능통과혈뇌병장진입뇌,병재문상체、하구뇌、액협피질、해마、소뇌등D4수체분포구역유교고적섭취솔,주약2 min후해마、하구뇌、문상체、액협피질、소뇌、뇌교적방사성분별체(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,단조단분포분별위(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.결론 ~(18)F-FDTP능통과대서혈뇌병장진입뇌,단기가능대뇌내제D4수체외적기타수체역유일정친화성.
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.