Brain kinetics of L-[?-11 C]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.

Stimulation of dopa decarboxylase activity in striatum of healthy human brain secondary to NMDA receptor antagonism with a low dose of amantadine

“…Tissue slope-intercept plots for FDOPA (Hartvig et al, 1991;Hoshi et al, 1993) were plotted for the four telencephalic ROIs. In the calculation of ordinate values, the radioactivity concentrations in CB were subtracted from those in each ROI to correct for the presence of non-specific background tissue radioactivity -i.e.…”

6-[18F]fluoro-l-DOPA Metabolism in Living Human Brain: A Comparison of Six Analytical Methods

“…Brooks et al (1990a,b), who used FDOPA, found the plot to be linear between 30 and 90 min of real time. Hartvig et al (1991), who used L-[!3_ 11 C]DOPA, found the plot to be linear after 5 min of "integral time." In this study, we found the plot more linear between 30 and 90 min (the 30-90-min analysis) than between 5 and 90 min (the 5-90-min analysis) because the slope declined during the early phase of the study and reached an asymptote around 30 min (Fig.…”

PET Studies of Cerebral Levodopa Metabolism: A Review of Clinical Findings and Modeling Approaches

“…4). Whatever it may be called, the slope of the reference tissue graphic analysis implicitly assumes that the fraction of FDOPA in the reference tissue remains constant over time (Hartvig and others 1991), whereas it is known that within 30 minutes after FDOPA injection, OMFD becomes the predominant Healthy subjects 0.0041 ± 0.0012 0.0037 ± 0.0015 Schizophrenia 0.0080 ± 0.0038 0.0063 ± 0.0029…”