^(18)F-胆碱类似物的制备及动物体内分布研究

Preparation of ^(18)F-choline analogue and its biodistribution in animals

目的 研制肿瘤显像剂18F标记胆碱类似物 2 18F 氟乙基 二甲基 2 氧乙基铵盐(FECH)。方法 通过两步反应制备FECH。18F-与乙二醇二对甲苯磺酸酯发生亲核取代反应 ,生成2 18F 氟代乙醇 2 对甲苯磺酸酯 ,后者与N ,N 二甲基乙醇胺反应制成FECH。测定FECH放化纯度及其正常小鼠与荷瘤裸鼠体内生物分布。结果 FECH放射化学产率为 2 5 % ,总放化合成时间为 80min ,放射化学纯度 >99%。FECH在小鼠体内血液清除快 ,肝、肾、膀胱和胰腺有高放射性摄取 ,脑、心肌、胃、肠道及骨骼放射性摄取较低。有较高的肿瘤 /血液、肿瘤 /脑、肿瘤 /心脏、肿瘤 /胃及肿瘤 /肌肉放射性比值。结论 18F FECH可望用于某些肿瘤的PET显像。

Objective To develop a 18 F labeled choline analogue, 2- 18 F-fluoroethyl-dimethyl-2-oxyethylammonium (FECH), a tumor imaging agent. Methods FECH was prepared via two steps. The nucleophilic displacement reaction of no-carrier-added 18 F-fluoride with 1,2-bis(tosyloxy)ethane gave the intermediate, 1- 18 F-fluoro-2-(tosyloxy)ethane. Then, coupling of 1- 18 F-fluoro-2-(tosyloxy)ethane with neat dimethylethano lamine gave FECH. Radiochemical purity and biodistributions in normal mice and nude mice bearing cancer cell were determined. Results FECH was synthesized in about 25% radiochemical yield with decay-correction and more than 99% radiochemical purity with a total radiosynthesis time of 80 min. Biodistributions of FECH in normal mice and nude mice were as follows: rapid blood clearance; high uptake in the liver, kidney, bladder and pancreas; low uptake in the brain, myocardium, stomach, intestine and bone; high tumor to blood, tumor to brain, tumor to heart, tumor to stomach, tumor to muscle radioactivity ratios were obtained. Conclusions A simple and practical synthesis protocoel for FECH is achieved. Biodistribution of FECH in mice is very similar to that of 11 C choline reported in literatures, FECH is promising to be an agent in diagnosis of tumors with PET imaging.