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 measure the central dopaminergic function in many species, including humans and monkeys. For transport across the blood brain barrier (BBB), FDOPA competes with plasma large neutral amino acids (LNAA). In this article we evaluate the effects of normal physiological LNAA concentration 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 sabaeus, n = 19) were fasted overnight before FDOPA positron emission tomography scans. Blood samples were drawn for LNAA determination, metabolite analysis, and compartmental modeling. The estimated K1 and Ki were both negatively correlated with LNAA concentrations (r2 = 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 was reduced by 33%, for Ki by 40%). Experiments with amino acid loading on an additional six animals indicate that BBB transport can be described 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.
Stout
D B
DB
Department of Molecular and Medical Pharmacology, UCLA School of Medicine 90095-6948, USA.
Huang
S C
SC
Melega
W P
WP
Raleigh
M J
MJ
Phelps
M E
ME
Barrio
J R
JR
D000596:Amino Acids / Q000097:blood*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000097:blood; D000882:Haplorhini; D006801:Humans; D007700:Kinetics; D014055:Tomography, Emission-Computed
D000596:Amino Acids; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine