THE TRANSPORT OF L-6-FLUORODOPA AND ITS METABOLITES FROM BLOOD TO CEREBROSPINAL-FLUID AND BRAIN

The transport of L-6-fluorodopa and its major metabolites from the blo od to the brain, cerebrospinal fluid (CSF), and muscle was studied in carbidopa-pretreated cynomolgus monkeys. A bolus intravenous injection of F-18-L-6-fluorodopa was followed by serial positron emission tomog raphy scans and sampling of cisternal CSF and arterial blood. The rela tive concentrations of L-6-fluorodopa and its metabolites were determi ned in blood plasma and CSF by high-performance liquid chromatography. Raising the blood concentration of phenylalanine by intraperitoneal i njection markedly reduced the accumulation of tracer in the brain. Thi s indicates that L-6-fluorodopa and 3-O-methylfluorodopa, like native L-dopa and its O-methylated derivative, are transported at the brain c apillary by the large neutral amino acid carrier-mediated system, whic h is subject to saturation and competition by other large neutral amin o acids (such as phenylalanine) at physiological plasma concentrations . In contrast, administration of phenylalanine had no effect on the ac cumulation of tracer either in muscle, or as L-6-fluorodopa and 3-O-me thylfluorodopa, in CSF. This suggests that the transport of L-dopa and its derivatives at the blood-CSF barrier differs from the transport a t the blood-brain barrier and also that measurement of CSF L-dopa is n ot a good index of the transport and pharmacokinetics of L-dopa in the brain. However, the effect of phenylalanine administration in reducin g the concentration of fluorohomovanillic acid in the CSF suggests tha t the concentration of homovanillic acid in the CSF is an accurate ref lection of dopamine turnover in the brain.