DEVELOPMENT OF RADIOPHARMACEUTICALS BASED ON THE BIOCHEMICAL FUNCTIONS OF ASCORBIC ACID

用[^<18>F]-氟离子亲核置换环硫酸盐，以15%的放射化学产率，一锅法合成了6-脱氧-6-[^<18>F]氟- l -抗坏血酸（^<18>F- dfa）。对F-DFA≤18 b>的大鼠进行的组织分布研究显示，已知l -抗坏血酸浓度较高的肾上腺、肾脏和肝脏器官对放射性的吸收较高。在静脉注射后10 - 120分钟，观察到脑内活动的缓慢和低吸收。^<18 b> F-DFA在3-甲基胆碱诱导的纤维肉瘤小鼠和移植的RG-C6脑肿瘤大鼠体内的行为表明其在肿瘤中的蓄积能力。比较正常大鼠和抗坏血酸缺乏ODS大鼠体内^<18>F-DFA的组织积累情况表明，大鼠体内内源性抗坏血酸不影响^<18>F-DFA的体内行为。采用脑缺血模型研究^<18 b>的F-DFA在脑内的分布。采用切断椎动脉后用微血管钳闭塞颈动脉20 min的方法诱导大鼠全身缺血。在缺血期结束后第5天，观察到注射^<18 b> F-DFA后，大脑皮层、下丘脑和杏仁核的放射性摄取增加。提示^<18 b>的F-DFA可能在脑缺血后神经损伤的修复机制中起重要作用。因此，基于l -抗坏血酸在正电子发射断层扫描中的生化功能，^<18 b> F-DFA似乎具有作为脑放射性药物的巨大潜力。

A one-pot synthesis of 6-deoxy-6-[^<18>F]fluoro-L-ascorbic acid (^<18>F-DFA) has been developed via nucleophilic displacement of a cyclic sulfate with [^<18>F]- fluoride ion in 15% radiochemical yield. Tissue distribution studies with ^<18>F-DFA in rats showed high uptake of radioactivity in the adrenals, kidneys and liver-organs known to have high concentration of L-ascorbic acid. The slow and low uptake of activity in the brain was observed between 10 and 120 min after i.v. injection. In vivo behavior of ^<18>F-DFA in mice bearing 3- methylcholanthrene-induced fibrosarcoma, and in rats bearing transplanted RG-C6 tumor in brain demonstrated its ability to accumulate in the tumors. Comparison of tissue accumulation of ^<18>F-DFA in normal rats and ascorbic acid deficient ODS rats indicated that endogenous ascorbic acid in rats does not affect the in vivo behavior of ^<18>F-DFA.Regional brain distribution of ^<18>F-DFA was investigated by using in vivo model of cerebral ischemia. Global ischemia was induced in rats by cutting arteiae vertebralis, and then occluding carotid arteries with a microvascular clamp for 20 min. Increased uptake of radioactivity in the cerebral cortex, hypothalamus and amygdala followed by injection of ^<18>F-DFA was observed at 5 days after the termination of the ischemic period. This finding suggests that ^<18>F-DFA may play an important role in repair mechanism of neural injury after cerebral ischemia. Thus, ^<18>F-DFA seemingly has a great potential as a brain radiopharmaceutical based on the biochemical functions of L-ascorbic acid for positron emission tomography.