DEVELOPMENT OF RADIOPHARMACEUTICALS BASED ON THE BIOCHEMICAL FUNCTIONS OF ASCORBIC ACID

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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.