Positron emission tomographic studies on aromatic L-amino acid decarboxylase activity in vivo for L-dopa and 5-hydroxy-L-tryptophan in the monkey brain.
The regional brain kinetics following 5-hydroxy-L-(beta-11 C)tryptophan and L-(beta-11 C)DOPA intravenous injection was measured in twelve Rhesus monkeys using positron emission tomography (PET). The radiolabelled compounds were also injected together with various doses of unlabelled 5-hydroxy-L-tryptophan or D-DOPA. The radioactivity accumulated in the striatal region and the rate of increased utilization with time was calculated using a graphical method with back of the brain as a reference region. The rate constants for decarboxylation were 0.0070 +/- 0.0007 (S. D) and 0.0121 +/- 0.0010 min-1 for 5-hydroxy-L-(beta-11 C)tryptophan and L-(beta-11 C)DOPA, respectively. After concomitant injection with unlabelled 5-hydroxy-L-tryptophan, the rate constant of 5-hydroxy-L-(beta-11 C)tryptophan decreased dose-dependently and a 50 percent reduction was seen with a dose of about 4 mg/kg of unlabelled compound. A decreased utilization rate of L-(beta-11 C)DOPA was seen only after simultaneous injection of 30 mg/kg of either L-DOPA or 5-hydroxy-L-tryptophan. This capacity limitation was most likely interpreted as different affinity of the striatal aromatic amino acid decarboxylase for L-DOPA and 5-hydroxy-L-tryptophan, respectively.
Hartvig
P
P
Hospital Pharmacy, University Hospital, Uppsala, Sweden.
Tedroff
J
J
Lindner
K J
KJ
Bjurling
P
P
Chang
C W
CW
Tsukada
H
H
Watanabe
Y
Y
Långström
B
B
D006916:5-Hydroxytryptophan / Q000378:metabolism* / Q000493:pharmacokinetics; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging* / Q000201:enzymology*; D005260:Female; D007980:Levodopa / Q000378:metabolism* / Q000493:pharmacokinetics; D008253:Macaca mulatta; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism; D014055:Tomography, Emission-Computed
D007980:Levodopa; D006916:5-Hydroxytryptophan; D001142:Aromatic-L-Amino-Acid Decarboxylases