title: Regional brain kinetics of 6-fluoro-(beta-11C)-L-dopa and (beta-11C)-L-dopa following COMT inhibition. A study in vivo using positron emission tomography.
abstract: The regional brain kinetics of (beta-11C)-L-dopa and 6-fluoro-(beta-11C)-L-dopa was measured in six Rhesus monkeys using positron emission tomography (PET). Radioactivity accumulated specifically in the striatal region and the increase in L-dopa-derived radioactivity utilization with time was calculated using surrounding brain as a reference area, this being devoid of dopaminergic activity. The rate constant for selective striatal utilization i.e. grossly decarboxylation was 0.0110 +/- 0.0007 (S.D) and 0.0057 +/- 0.0006 min-1 for (beta-11C)-L-dopa and 6-fluoro-(beta-11C)-L-dopa, respectively. After pretreatment of the monkeys with the peripherally and centrally active catecholamine-O-methyl transferase (COMT) inhibitor Ro 40-7592 10 mg/kg, the decarboxylation rate remained unchanged (0.0112 +/- 0.0015 min-1) for (beta-11C)-L-dopa, whereas an increase in rate was measured for 6-fluoro-(beta-11C)-L-dopa (0.0092 +/- 0.0015 min-1). Differences in the distribution of radiolabelled metabolites i.e. the corresponding O-methyl-L-dopa in the reference area is most probably the reason for the difference in calculated decarboxylation rate seen between the radiotracers. The higher decarboxylation rate measured for 6-fluoro-(beta-11C)-L-dopa after blockade of COMT shows that the radiolabelled metabolites i.e. 6-fluoro-O-methyl-(beta-11C)-L-dopa significantly contributes to background radioactivity.
authors.affiliation: Hospital Pharmacy, University Hospital, Uppsala, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Hartvig
authors.forename: K J
authors.initials: KJ
authors.lastname: Lindner
authors.forename: J
authors.initials: J
authors.lastname: Tedroff
authors.forename: P
authors.initials: P
authors.lastname: Bjurling
authors.forename: K
authors.initials: K
authors.lastname: Hörnfelt
authors.forename: B
authors.initials: B
authors.lastname: Långström
mesh_terms: D000818:Animals; D001577:Benzophenones / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006207:Half-Life; D008253:Macaca mulatta; D008750:Methyldopa / Q000493:pharmacokinetics; D009596:Nitrophenols; D000077867:Tolcapone; D014055:Tomography, Emission-Computed
chemical_list: D001577:Benzophenones; D002250:Carbon Radioisotopes; D065098:Catechol O-Methyltransferase Inhibitors; D009596:Nitrophenols; C043437:fluorodopa F 18; D008750:Methyldopa; D004295:Dihydroxyphenylalanine; D000077867:Tolcapone; D002394:Catechol O-Methyltransferase