Kinetics of in vitro decarboxylation and the in vivo metabolism of 2-¹⁸F- and 6-¹⁸F-fluoroDOPA in the hooded rat

Abstract

The metabolisms of l-18F-2-fluoro-DOPA (l-2-18F-DOPA) and l-18F-6-fluoro-DOPA (l-6-18 F-DOPA) were compared in vitro and in vivo in the carbidopa-pretreated male hooded rat. In vivo, the sole metabolites in plasma were O-methylated derivatives. The peripheral formation of the O-methylated derivative of l-2-18F-DOPA was approximately twice as great as that for the 6-isomer. Animals were killed at 10 and 60 min after administration of the 18F-DOPAs, and samples of striatum and vermis were analyzed by HPLC. l-2-18F-DOPA passed less readily into brain than did l-6-18F-DOPA. Whereas significant amounts of 6-18F-fluorodopamine and metabolites were formed in the striatum, no decarboxylated derivatives of l-2-18F-DOPA were found. Determination of the Michaelis-Menten kinetic constants for aromatic amino acid decarboxylase (AADC, EC 4.1.1.26) indicated that the Km for l-2-18F-DOPA (982 ± 115 μM) was considerably higher than that for l-6-18F-DOPA (101 ± 22 μM). The low substrate affinity for AADC and the relatively more rapid rate of O-methylation in the periphery account for the lack of formation of 2-18F-fluorodopamine in vivo. The ratio of total radioactivity between striatum and other brain regions is related to the decarboxylation of radiolabeled tracer and the relative persistence of the decarboxylated derivatives in the striatum. Since l-2-18F-DOPA is not decarboxylated in rat striatum, it is not a promising agent for the study of cerebral DOPA metabolism in humans by means of positron emission tomography. © 1988.