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  • 1
    ISSN: 1435-1463
    Schlagwort(e): (β-11C)-L-dopa ; 6-fluoro-(β-11C)-L-dopa ; positron emission tomography ; catechol-O-methyl transferase ; monkeys
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The regional brain kinetics of (β-11C)-L-dopa and 6-fluoro-(β-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 min1 for (β-11C)-L-dopa and 6-fluoro-(β-11C)-L-dopa, respectively. After pre-treatment 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 (β11C)-L-dopa, whereas an increase in rate was measured for 6-fluoro-(β-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-(β-11C)-L-dopa after blockade of COMT shows that the radiolabelled metabolites i.e. 6-fluoro-O-methyl-(β-11C)-L-dopa significantly contributes to background radioactivity.
    Materialart: Digitale Medien
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  • 2
    ISSN: 1435-1463
    Schlagwort(e): 5-Hydroxy-(β-11 C)-L-tryptophan ; monkey ; positron emission tomography ; enzyme inhibition ; decarboxylation rate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 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-(β-11C)-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-(β-11 C)-L-tryptophan in PET-studies of brain serotonin metabolism in health and disease.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1435-1463
    Schlagwort(e): 5-Hydroxy-L-(β-11 C)tryptophan ; L-(β-11 C)DOPA ; positron emission tomography ; aromatic amino acid decarboxylase ; monkeys
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The regional brain kinetics following 5-hydroxy-L-(β-11 C)tryptophan and L-(β-11 C)DOPA intravenous injection was measured in twelve Rhesus monkeys using positron emission tomography (PET). The radiolabelled compounds were also injected together with various doses of unlabelled 5-hydroxy-L-tryptophan or L-DOPA. The radioactivity accumulated in the striatal region and the rate of increased utilization with time was calculated using a graphical method with back of the brain as a reference region. The rate constants for decarboxylation were 0.0070 ± 0.0007 (S. D) and 0.0121±0.0010min−1 for 5-hydroxy-L-(β-11C)tryptophan and L-(β-11 C)DOPA, respectively. After concomitant injection with unlabelled 5-hydroxy-L-tryptophan, the rate constant of 5-hydroxy-L-(β-11 C)tryptophan decreased dose-dependently and a 50 percent reduction was seen with a dose of about 4mg/kg of unlabelled compound. A decreased utilization rate of L-(β-11 C)DOPA was seen only after simultaneous injection of 30 mg/kg of either L-DOPA or 5-hydroxy-L-tryptophan. This capacity limitation was most likely interpreted as different affinity of the striatal aromatic amino acid decarboxylase for L-DOPA and 5-hydroxy-L-tryptophan, respectively.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Journal of neural transmission 85 (1991), S. 11-17 
    ISSN: 1435-1463
    Schlagwort(e): Tomography ; monkey ; L-DOPA ; aromatic L-amino acid decarboxylase ; catechol-O-methyltransferase ; Parkinson's disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Positron emission tomography (PET) following intravenous administration of β-[11 C]-L-DOPA provides a method of assessing regional cerebral uptake and utilization of levodopa. Cerebral levodopa kinetics in the rhesus monkey were investigated after the inhibition of catechol-O-methyltransferase (COMT) with RO 40-7592, and after coadministration of the peripheral aromatic L-amino acid decarboxylase (AADC) inhibitors benserazide and carbidopa. Pretreatment with RO 40-7592 (10 mg/kg), benserazide (10 mg/kg) or carbidopa (3.5 mg/kg) did not change striatal k3, which mainly reflects the ability for the brain tissue to convert [11C]-L-DOPA to [11C]-dopamine, although the brain's uptake of radioactivity increased substantially after pretreatment with the AADC inhibitors. When benserazide was coadministered with RO 40-7592 (10 mg/kg) a dose-dependent decrease in striatal k3 was measured with an apparent ED50 of 3 mg/kg. No such effect was indicated after pretreatment with the combination of RO 40-7592 (10 mg/kg) and carbidopa (3.5 mg/kg). The possible negative interactions of coadministration with COMT inhibitors and predominantly peripherally acting AADC inhibitors must be considered when used in the therapy of Parkinson's disease.
    Materialart: Digitale Medien
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  • 5
    ISSN: 1435-1463
    Schlagwort(e): Amphetamine ; [11C] ; L-DOPA ; raclopride ; N-methylspiperone ; CBF ; PET ; monkeys
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Positron emission tomography (PET) was used in a multitracer protocol to evaluate D-amphetamine induced effects on dopamine biosynthesis rate and release in propofol anesthetized Rhesus monkeys.l-[β-11C]DOPA was used as biochemical probe to study the brain dopamine biosynthesis rate whilst dopamine release was followed by the binding displacement of the [11C]-radiolabelled dopamine receptor antagonists, raclopride and N-methylspiperone. Studies were performed with either a constant rate intravenous infusion of D-amphetamine aiming at plasma concentrations of 0.2 to 25 ng/ml or with intravenous bolus doses of 0.1 and 0.4 mg/ kg. Decreased binding of the dopamine receptor antagonists was measured in both modes of D-amphetamine administration but notably [11C]N-methylspiperone was less able to sense D-amphetamine induced release of dopamine. At plasma concentrations aimed above 1 ng/ml a levelling off of the binding of [11C]raclopride at 68 ± 8.1% of the baseline value indicated that displacement was only possible from a fraction of the binding sites. Amphetamine was observed to increase the rate constant forl-[β-11C]DOPA utilization in the brain. This was most likely due to an acutely induced subsensitivity of presynaptic dopamine receptors.l-[β-11C]DOPA and [11C]raclopride were found suitable to indicate changes in dopamine synthesis rate and release respectively using PET and can be used to mirror drug-induced changes of brain dopaminergic function.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1435-1463
    Schlagwort(e): PET ; anesthetics ; ketamine ; isoflurane ; dopamine D2 receptor ; monkey
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The effects of anesthesia on dopamine D2 receptor binding in the rhesus monkey brain were examined using positron emission tomography. The bindings of11C-N-methylspiperone (NMSP) and11C-raclopride (RAC) were measured under controlled ketamine or isoflurane anesthesia. The binding of11C-NMSP was significantly lower in the striatum anesthetized with isoflurane than with ketamine. There was a smaller change in the binding of11C-RAC than of11C-NMSP. These findings suggest that changes in11C-NMSP or11C-RAC binding induced by anesthetics were not due solely to changes in the competition of endogenous dopamine.
    Materialart: Digitale Medien
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