UBC Theses and Dissertations
The metabolism of fluorodopa Cumming, Paul
Experiments were conducted to characterize the metabolism of ¹⁸F-6-fluorodopa (¹⁸F-D0PA), a compound used as a tracer for the study of dopamine metabolism in human subjects by means of positron emission tomography (PET). Analysis of plasma from carbidopa pretreated humans, monkeys and rats showed that ¹⁸F-D0PA disappeared rapidly and that the principal plasma metabolite was 0-methyl-¹⁸F-D0PA. The kinetics of both ¹⁸F-D0PA and total ¹⁸F disappearance in the three species were found to be biexponential. In human subjects, some components of plasma ¹⁸F-D0PA metabolism were found to be age dependent. Inhibition of catechol-0-methyltransferase (COMT) with U-0521 increased greatly the persistance of ¹⁸F-D0PA in plasma of the rat. Cerebral tissues of the male hooded rat were analyzed by high preformance liquid chromatography at various times after ¹⁸F-D0PA administration. Me-¹⁸F-D0PA was found to accumulate rapidly in striatum, cortex and cerebellum. Striatum differed from other tissues in that radioactivity levels were maintained at a fairly constant level for two hours, during which time radioactivity washed out of other brain regions. This radiocontrast was found to be due to the formation of ¹⁸F-fluorodopamine and subsequent metabolites in striatum. Inhibition of COMT with U-0521 increased the amount of ¹⁸F-fluorodopamine in striatum by 50% over a 90 minutes period, but this only produced a marginal increase in radiocontrast because of the remaining background activity due to Me-¹⁸F-D0PA. The kinetics of the decarboxylation of 6-¹⁸F-D0PA were determined in vitro to be very similar to literature values reported for L-DOPA. In contrast, 2-¹⁸F-fluorodopa was a poor substrate for the decarboxylase.
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