Brain kinetics of 11 C-labelled L-tryptophan and 5-hydroxy-L-tryptophan in the rhesus monkey. A study using positron emission tomography.
5-Hydroxy-L-tryptophan labelled with 11 C is introduced as a tracer for the in vivo assessment of brain serotonin synthesis in the Rhesus monkey using positron emission tomography, PET. Increasing radioactivities were seen in the striatal area in contrast to that seen in other brain regions. Following 11 C-labelled L-tryptophan an even spread of brain radioactivity was seen. This selective increase most probably results from the decarboxylation of tracer and retention of formed products since no striatal increase of radioactivity was seen when 5-hydroxy-L-tryptophan labelled with 11 C in the carboxy-position was administered. Furthermore, pretreatment of the monkey with a centrally active decarboxylase inhibitor (NSD 1015, 10 mg/kg) did not lead to increased striatal radioactivities after the administration of 5-hydroxy-(beta-11 C)-L-tryptophan. The selective utilization of the radiotracer in the striatal area increased with a rate constant calculated to be 0.0055 +/- 0.0015 min-1 (n = 5) using the surrounding brain as reference area. A non-significant influence of radiolabelled metabolites to the rate constants measured was shown after pretreatment of the monkeys with selective and non-selective monoamine oxidase inhibitors, respectively. These results may give a basis for the use of the new tracer 5-hydroxy-(beta-11 C)-L-tryptophan in PET-studies of brain serotonin metabolism in health and disease.
Hartvig
P
P
Hospital Pharmacy, University Hospital, Uppsala, Sweden.
Lindner
K J
KJ
Tedroff
J
J
Andersson
Y
Y
Bjurling
P
P
Långström
B
B
D006916:5-Hydroxytryptophan / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D008253:Macaca mulatta; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D014055:Tomography, Emission-Computed; D014364:Tryptophan / Q000493:pharmacokinetics*
D002250:Carbon Radioisotopes; D006834:Hydrazines; D008996:Monoamine Oxidase Inhibitors; D014364:Tryptophan; C004297:3-hydroxybenzylhydrazine; D006916:5-Hydroxytryptophan