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The time course of metabolites in human plasma after 6-[18F]fluoro-l-m-tyrosine administration

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Abstract.

For the investigation of intracerebral dopamine metabolism, 6-[18F]fluoro-l-m-tyrosine (FmT) has been proposed as an alternative tracer that, unlike 6-[18F]fluoro-l-dopa, is not subjected to O-methylation. We have studied the time course of FmT and its labelled metabolites in plasma after intravenous injection into humans, employing a method that we have developed and validated to analyze labelled metabolites of FmT in plasma. The study population comprised 38 subjects, 14 of whom were taking an aromatic amino acid decarboxylase inhibitor (carbidopa), and obtained arterialized venous blood samples at various times after an intravenous injection of between 185 and 370 MBq of FmT. The major metabolite of FmT present in plasma was 6-[18F]fluoro-3-hydroxyphenylacetic acid. The time course of the fraction of radioactivity in plasma attributable to FmT was fitted well by the decay of two exponential functions. The fast component of the decay accounted for 40%–50% of the radioactivity and had a half-life of about 5 min. The slow component of the decay had a half-life of about 6 h in the subjects not taking carbidopa and 20 h in the patients taking carbidopa. When the total available FmT was calculated for each individual subject and expressed as a proportion of total radioactivity, this quantity did not differ significantly from that determined from the corresponding population mean. There was significantly more (15% on average) FmT available over the course of the 2-h experiment in the group pretreated with carbidopa. Our results demonstrate that the major metabolite in plasma after an intravenous injection of FmT is 6-[18F]fluoro-3-hydroxyphenylacetic acid. The clearance of FmT from plasma compares well with the clearance of intravenously administered levodopa. Carbidopa increases significantly the availability of FmT in plasma. These results verify, in a large number of human subjects, earlier analyses of FmT metabolism in other species. We validate a population-derived approach that can adequately describe the time course of FmT in plasma, alleviating the need for metabolite analysis.

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Received 2 March and in revised form 25 June 1999

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Wahl, L., Chen, J., Thompson, M. et al. The time course of metabolites in human plasma after 6-[18F]fluoro-l-m-tyrosine administration. Eur J Nucl Med 26, 1407–1412 (1999). https://doi.org/10.1007/s002590050472

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  • DOI: https://doi.org/10.1007/s002590050472

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