TY - JOUR
T1 - Metabolism and blood-brain clearance of l-3,4-dihydroxy-[3H]phenylalanine ([3H]DOPA) and 6-[18F]fluoro-l-DOPA in the rat
AU - Cumming, Paul
AU - Ase, Ariel
AU - Diksic, Mirko
AU - Harrison, Joel
AU - Jolly, Dean
AU - Kuwabara, Hiroto
AU - Laliberté, Christine
AU - Gjedde, Albert
PY - 1995/9/28
Y1 - 1995/9/28
N2 - 6-[18F]fluoro-l-DOPA (FDOPA) has been used as a tracer for the cerebral activity of l-3,4-dihydroxyphenylalanine (DOPA)-decarboxylase in studies of positron emission tomography (PET). However, the substitution of fluorine on the aromatic ring may alter the disposition and metabolism of FDOPA from that of endogenous DOPA. In the present study, the kinetics of the peripheral metabolism and the facilitated unidirectional blood-brain clearance of [3H]DOPA and FDOPA were compared in Wistar rats pretreated with carbidopa. In arterial plasma, FDOPA was O-methylated with an apparent rate constant (0.031 min-1) 3-fold that of [3H]DOPA in the same rats. The O-methylated metabolite of FDOPA (OMe-FDOPA) was eliminated from plasma at a rate constant (0.018 min-1) 3-fold that of OMe-[3H]DOPA. The mean unidirectional blood-brain clearance of FDOPA (4.5 mL · hg-1 · min-1) in six brain regions was 60% higher than that of [3H]DOPA.
AB - 6-[18F]fluoro-l-DOPA (FDOPA) has been used as a tracer for the cerebral activity of l-3,4-dihydroxyphenylalanine (DOPA)-decarboxylase in studies of positron emission tomography (PET). However, the substitution of fluorine on the aromatic ring may alter the disposition and metabolism of FDOPA from that of endogenous DOPA. In the present study, the kinetics of the peripheral metabolism and the facilitated unidirectional blood-brain clearance of [3H]DOPA and FDOPA were compared in Wistar rats pretreated with carbidopa. In arterial plasma, FDOPA was O-methylated with an apparent rate constant (0.031 min-1) 3-fold that of [3H]DOPA in the same rats. The O-methylated metabolite of FDOPA (OMe-FDOPA) was eliminated from plasma at a rate constant (0.018 min-1) 3-fold that of OMe-[3H]DOPA. The mean unidirectional blood-brain clearance of FDOPA (4.5 mL · hg-1 · min-1) in six brain regions was 60% higher than that of [3H]DOPA.
KW - 6-fluoro-l-DOPA
KW - DOPA
KW - blood-brain permeability
KW - catechol-O-methyltransferase
KW - kinetics
KW - positron emission tomography
UR - http://www.scopus.com/inward/record.url?scp=0028875078&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028875078&partnerID=8YFLogxK
U2 - 10.1016/0006-2952(95)00216-M
DO - 10.1016/0006-2952(95)00216-M
M3 - Article
C2 - 7575677
AN - SCOPUS:0028875078
SN - 0006-2952
VL - 50
SP - 943
EP - 946
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 7
ER -