Journal ArticleDOI
Brain kinetics of L-[beta-11C]dopa in humans studied by positron emission tomography.
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TLDR
11C-labelled L-DOPA is introduced as an alternative to the well-established L-6-[18 F]fluoro-Dopa methodology in clinical studies on brain L- DOPA uptake and dopamine synthesis, indicating competition for transport across the blood-brain barrier.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.read more
Citations
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Journal ArticleDOI
Increased dopamine synthesis rate in medial prefrontal cortex and striatum in schizophrenia indicated by L-(β-11C) DOPA and PET
Leif Lindström,O. Gefvert,Gisela E. Hagberg,T. Lundberg,Mats Bergström,Per Hartvig,Bengt Långström +6 more
TL;DR: The results indicate that the synthesis of dopamine is elevated within the striatum and parts of medial prefrontal cortex in schizophrenia.
Journal Article
PET evaluation of the dopamine system of the human brain.
Nora D. Volkow,Joanna S. Fowler,Samuel J. Gatley,J. Logan,G.J. Wang,Yu-Shin Ding,Stephen L. Dewey +6 more
TL;DR: This paper summarizes the different tracers and experimental strategies developed to evaluate the various elements of the dopamine system in the human brain with PET and their applications to clinical research.
Journal ArticleDOI
A Test of the Transdiagnostic Dopamine Hypothesis of Psychosis Using Positron Emission Tomographic Imaging in Bipolar Affective Disorder and Schizophrenia
Sameer Jauhar,Sameer Jauhar,Matthew M. Nour,Matthew M. Nour,Mattia Veronese,Maria Rogdaki,Ilaria Bonoldi,Ilaria Bonoldi,Matilda Azis,Federico Turkheimer,Philip McGuire,Philip McGuire,Allan H. Young,Oliver D. Howes,Oliver D. Howes,Oliver D. Howes +15 more
TL;DR: Findings are consistent with a transdiagnostic role for dopamine dysfunction in the pathoetiology of psychosis and suggest dopamine synthesis capacity as a potential novel drug target for bipolar disorder and schizophrenia.
Journal ArticleDOI
PET Studies of Cerebral Levodopa Metabolism: A Review of Clinical Findings and Modeling Approaches
Yoshitaka Kumakura,Paul Cumming +1 more
TL;DR: Using a constrained compartmental model, FDOPA-PET recordings can be used to calculate the relative activity of the enzyme DOPA decarboxylase in living brain, and an index of steady-state trapping of fluorodopamine in synaptic vesicles is obtained.
Journal ArticleDOI
The test-retest reliability of 18F-DOPA PET in assessing striatal and extrastriatal presynaptic dopaminergic function.
Alice Egerton,Arsime Demjaha,Arsime Demjaha,Philip McGuire,Mitul A. Mehta,Mitul A. Mehta,Oliver D. Howes,Oliver D. Howes +7 more
TL;DR: The utility of 18F-DOPA PET in assessing dopaminergic function in the striatum and select extrastriatal areas is confirmed but the limitations in using this approach to measure dopamine function in low uptake extrastiatal brain areas are highlighted.
References
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Journal ArticleDOI
Calculation of cerebral glucose phosphorylation from brain uptake of glucose analogs in vivo: A re-examination
TL;DR: The 2-deoxyglucose (2-DG) method of functional neuroanatomical mapping25 was re-examined in order to obtain physical descriptions of the transfer constants K1 and k2 and estimate the changes of the 'lumped constant' with the condition of the experimental animals.
Journal ArticleDOI
Brain dopamine metabolism in patients with Parkinson's disease measured with positron emission tomography.
Klaus L. Leenders,A J Palmer,Niall Quinn,J C Clark,G. Firnau,E.S. Garnett,Claude Nahmias,Terry Jones,C. D. Marsden +8 more
TL;DR: The capacity of the striatum to retain tracer was severely impaired in patients compared to controls and this may reflect a reduction of striatal dopamine storage in Parkinson's disease.