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The metabolism of fluorodopa Cumming, Paul
Abstract
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.
Item Metadata
| Title |
The metabolism of fluorodopa
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| Creator | |
| Publisher |
University of British Columbia
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| Date Issued |
1986
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| Description |
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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| Genre | |
| Type | |
| Language |
eng
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| Date Available |
2010-06-20
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| Provider |
Vancouver : University of British Columbia Library
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| Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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| DOI |
10.14288/1.0096689
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| URI | |
| Degree | |
| Program | |
| Affiliation | |
| Degree Grantor |
University of British Columbia
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| Campus | |
| Scholarly Level |
Graduate
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| Aggregated Source Repository |
DSpace
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For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.