18 F-胆碱类似物的制备及动物体内分布研究

目的 研究肿瘤显像剂^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25％，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。

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

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.