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

For the investigation of intracerebral dopamine metabolism, 6-[F-18]fluoro- L-m-tyrosine (FmT) has ;been proposed as an alternative tracer that, unlike 6-[F-18]fluoro-L-dopa, is not subjected to O-methylation. We have studied the time course of FmT and its labelled metabolites in plasma after intrave nous injection into humans, employing a method that we have developed and v alidated to analyze labelled metabolites of FmT in plasma. The study popula tion comprised 38 subjects, 14 of whom were taking an aromatic amino acid d ecarboxylase 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-[F-18]f luoro-3-hydroxyphenylacetic acid. The time course of the fraction of radioa ctivity in plasma attributable to FmT was fitted well by the decay of two e xponential 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 componen t of the decay had a half-life of about 6 h in the subjects not taking carb idopa and 20 h in the patients taking carbidopa. When the total available F mT was calculated for each individual subject and expressed as a proportion of total radioactivity, this quantity did not differ significantly from th at determined from the corresponding population mean. There was significant ly more (15% on average) FmT available over the course of the 2-h experimen t in the group pretreated with carbidopa. Our results demonstrate that the major metabolite in plasma after an intravenous injection of FmT is 6-[F-18 ]fluoro-3-hydroxyphenylacetic acid. The clearance of FmT from plasma compar es well with the clearance of intravenously administered levodopa, Carbidop a increases significantly the availability of FmT in plasma. These results verify, in a large number of human subjects, earlier analyses of FmT metabo lism in other species. We validate a population-derived approach that can a dequately describe the time course of FmT in plasma, alleviating the need f or metabolite analysis.