6-^(18)F-多巴的制备及其大鼠体内分布研究

Preparation of 6-~ (18)F-DOPA and its biodistribution in rats

目的 制备PET显像剂 6 18F 多巴 ( 6 18F DOPA)并研究其在大鼠体内的生物分布。方法 使用小型回旋加速器生产18F离子 ,经亲核取代、手性相转移催化烷基化等 4步反应 ,合成得到无载体的 6 18F DOPA。 2 4只SD大鼠分为 6组 ,每只经尾静脉注射 1 .1 1MBq 6 18F DOPA ,经 5,30 ,6 0 ,90 ,1 2 0和 1 50min后分别处死 ,解剖 ,取有关组织、脏器称重并测定放射性计数。结果 6 18F DOPA合成的放化产率为 3.8%～ 7.5% (衰变校正后 ) ,合成时间 1 0 0min ,放化纯度大于 99%。大鼠体内生物分布显示纹状体内有明显的放射性浓集 ,而大脑、皮质、小脑中放射性较低 ;纹状体 /小脑放射性比值在 6 0min达 5.9;其他组织器官中的放射性快速清除 ,无明显浓集。结论 建立的 6 18F DOPA合成方法有效可靠 ,6 18F DOPA主要分布在纹状体内。

Objective To prepare the important PET tracer, 6-~ 18F-DOPA and to study its biodistribution in rats. Methods No-carrier-added ~ 18F was produced by a mini cyclotron and used as the radiolabeling reagent. 6-~ 18F-DOPA was successfully prepared after four reactions (nucleophilic substitution, reductive iodination, chiral phase-transfer catalysis and hydrolysis). Twenty-four rats were divided into 6 groups of four rats and each rat was injected iv with 1.11 MBq of 6-~ 18F-DOPA. At 5, 30, 60, 90, 120 and 150 min after injection, rats of the correspondant group were killed respectively, and radioactivity of various parts of the brain and different organs was counted. Results The radiochemical yield of this synthesis was 3.8%～7.5% with a synthesis time of 100 min and a high radiochemical purity(>99%). Biodistribution study in rats showed obvious concentration of radioactivity in the striatum and hippocampus and low distribution in cerebrum, cortex and cerebellum. The ratio of the radioactivity of striatum to cerebellum reached a peak value at 60 min. The clearance of this radiopharmaceutical from blood and other organs was fast (most of the radioactivity was cleared within 30 min). Conclusions The synthesis method is efficient; the accumulation of 6-~ 18F-DOPA in striatum is proved and that is the basis of its application in PET.