EFFECTS OF LARGE NEUTRAL AMINO-ACID-CONCENTRATIONS ON 6-[F-18]FLUORO-L-DOPA KINETICS

6-[F-18]Fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) has been used to m easure the central dopaminergic function in many species, including hu mans and monkeys. For transport across the blood brain barrier (BBB), FDOPA competes with plasma large neutral amino acids (LNAA). In this a rticle we evaluate the effects of normal physiological LNAA concentrat ion variation on BBB transport (K1) and the FDOPA uptake measurement, Ki. We also investigate a method for reducing the dependency of FDOPA quantitation on LNAA. Adult vervet monkeys (Cercopithecus aethiops sab aeus, n = 19) were fasted overnight before FDOPA positron emission tom ography scans. Blood samples were drawn for LNAA determination, metabo lite analysis, and compartmental modeling. The estimated K1 and Ki wer e both negatively correlated with LNAA concentrations (r(2) = 0.51 and 0.62, respectively). Using an adjustment to K1 and Ki based on these correlations, the LNAA dependency was reduced (SD of the data for K1 w as reduced by 33%, for Ki by 40%). Experiments with amino acid loading on an additional six animals indicate that BBB transport can be descr ibed using Michaelis-Menten kinetics. Results show a clear dependence of FDOPA uptake on plasma LNAA concentrations, which can be removed to increase the precision of FDOPA quantitation.