title: Brain kinetics of L-[beta-11C]dopa in humans studied by positron emission tomography.
abstract: The in vivo dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) labelled with 11C in the beta position has been used for positron emission tomography studies of L-DOPA utilization in the brain. The brain uptake and kinetics of L-[11C]DOPA-derived radioactivity were studied in healthy male volunteers, and the specific utilization, i.e. decarboxylation rate of L-[11C]DOPA in different brain areas, was quantified using a brain region devoid of specific L-[11C]DOPA utilization as reference. Total uptake of L-[11C]DOPA-derived radioactivity measured in the brain varied two- to three-fold between subjects, with highest radioactivity in the striatal region. Specific utilization of L-[11C]DOPA radioactivity in the striatal region and in the prefrontal cortex varied twofold between subjects. No specific utilization was observed in other regions of the brain. The uptake of radioactivity in the brain increased dose-dependently with the simultaneous administration of unlabelled L-DOPA up to 10 mg. On the other hand, a decrease in brain radioactivity uptake was measured after pretreatment with 1 mg/kg oral L-DOPA, indicating competition for transport across the blood-brain barrier. Benserazide 0.5 mg/kg orally increased somewhat the radioactivity uptake to the brain. None of these pharmacological perturbations demonstrated any clearcut effect on specific utilization of L-[11C]DOPA. Thus, 11C-labelled L-DOPA is introduced as an alternative to the well-established L-6-[18F]fluoro-DOPA methodology in clinical studies on brain L-DOPA uptake and dopamine synthesis.
authors.affiliation: Hospital Pharmacy, University Hospital, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Hartvig
authors.forename: H
authors.initials: H
authors.lastname: Agren
authors.forename: L
authors.initials: L
authors.lastname: Reibring
authors.forename: J
authors.initials: J
authors.lastname: Tedroff
authors.forename: P
authors.initials: P
authors.lastname: Bjurling
authors.forename: T
authors.initials: T
authors.lastname: Kihlberg
authors.forename: B
authors.initials: B
authors.lastname: Långström
mesh_terms: D000328:Adult; D001479:Basal Ganglia / Q000378:metabolism; D001545:Benserazide / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002421:Caudate Nucleus / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism; D005917:Globus Pallidus / Q000378:metabolism; D006801:Humans; D007980:Levodopa / Q000493:pharmacokinetics*; D008024:Ligands; D008297:Male; D008954:Models, Biological; D011699:Putamen / Q000378:metabolism; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D008024:Ligands; D007980:Levodopa; D001545:Benserazide