On the Rate of Decarboxylation of Dopa to Dopamine in Living Mammalian Brain<sup>a</sup>

Cumming, Paul; Deep, Paul; Rousset, Olivier; Evans, Alan C.; Gjedde, Albert

doi:10.1111/j.1749-6632.1997.tb48637.x

Cited by 13 publications

(14 citation statements)

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“…3). The dopaminergic ligands available can be used to assess synthesis capacity, receptor density as well as dynamic endogenous release of dopamine (Farde et al , 1987; Volkow et al , 1994; Cumming et al , 1997). These have been applied widely in Parkinson’s disease and other neurodegenerative conditions (Tai and Pavese, 2013), but have been used surprisingly little in TBI.…”

Section: Stratifying Patient Treatment Based On Catecholaminergic Funmentioning

confidence: 99%

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Catecholamines and cognition after traumatic brain injury

Jenkins

Mehta

Sharp

2016

Brain

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Section: Stratifying Patient Treatment Based On Catecholaminergic Funmentioning

confidence: 99%

“…18 F-DOPA can be used to assess dopamine synthesis in the presynaptic terminal (Cumming et al , 1997). In Parkinson’s disease, reductions in this tracer in the caudate correlate with impairments in neuropsychological performance (Bruck et al , 2001).…”

Section: Stratifying Patient Treatment Based On Catecholaminergic Funmentioning

confidence: 99%

Catecholamines and cognition after traumatic brain injury

Jenkins

Mehta

Sharp

2016

Brain

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“…The ratio of [ 18 F]fluorohomovanillic acid to [ 18 F]fluorodopamine was much higher in striatum of monkeys on the side of MPTP lesions, suggesting increased dopamine turnover in residual dopamine fibres (Melega et al, 1991b). The metabolism of labelled dopamine formed may also be accelerated in sporadic Parkinson's disease Table VI), perhaps due to compromised vesicular storage (Deep et al, 1997a). This phenomenon would tend to influence results obtained with linear methods assuming irreversible trapping of tracer in brain.…”

Section: Clinical Studies Of Movement Disorders and Normal Agingmentioning

confidence: 99%

“…We now review the state of development of compartmental metabolic models for [ 18 F]fluorodopa and other labelled substrates for dopa decarboxylase, with special emphasis on current controversies and on applications of these methods for clinical studies. Part of this study has been reported in conference proceedings (Cumming et al, 1997a).…”

Section: Introductionmentioning

confidence: 99%

Compartmental analysis of dopa decarboxylation in living brain from dynamic positron emission tomograms

Cumming

Gjedde

1998

Synapse

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102

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The trapping of decarboxylation products of radiolabelled dopa analogs in living human brain occurs as a function of the activity of dopa decarboxylase. This enzyme is now understood to regulate, with tyrosine hydroxylase, cerebral dopamine synthesis. Influx into brain of dopa decarboxylase substrates such as 6-[18F]fluorodopa and beta-[11C]dopa measured by positron emission tomography can be analyzed by solution of linear differential equations, assuming irreversible trapping of the decarboxylated products in brain. The isolation of specific physiological steps in the pathway for catecholamine synthesis requires compartmental modelling of the observed dynamic time-activity curves in plasma and in brain. The several approaches to the compartmental modelling of the kinetics of labelled substrates of dopa decarboxylase are now systematically and critically reviewed. Labelled catechols are extensively metabolized by hepatic catechol-O-methyltransferase yielding brain-penetrating metabolites. The assumption of a fixed blood-brain permeability ratio for O-methyl-6-[18F]fluorodopa or O-methyl-beta-[11C]dopa to the parent compounds eliminates several parameters from compartmental models. However, catechol-O-methyltransferase activity within brain remains a possible factor in underestimation of cerebral dopa decarboxylase activity. The O-methylation of labelled catechols is blocked with specific enzyme inhibitors, but dopa decarboxylase substrates derived from m-tyrosine may supplant the catechol tracers. The elimination from brain of decarboxylated tracer metabolites can be neglected without great prejudice to the estimation of dopa decarboxylase activity when tracer circulation is less than 60 minutes. However, elimination of dopamine metabolites from brain occurs at a rate close to that observed previously for metabolites of glucose labelled in the 6-position. This phenomenon can cause systematic underestimation of the rate of dopa decarboxylation in brain. The spillover of radioactivity due to the limited spatial resolution of tomographs also results in underestimation of dopa decarboxylase activity, but correction for partial volume effects is now possible. Estimates of dopa decarboxylase activity in human brain are increased several-fold by this correction. Abnormally low influx of dopa decarboxylase tracers in the basal ganglia is characteristic of Parkinson's disease and other movement disorders. Consistent with postmortem results, the impaired retention of labelled dopa is more pronounced in the putamen than in the caudate nucleus of patients with Parkinson's disease; this heterogeneity persists after correction for spillover. Current in vivo assays of dopa decarboxylase activity fail to discriminate clinically distinct stages in the progression of Parkinson's disease and are, by themselves, insufficient for differential diagnosis of Parkinson's disease and other subcortical movement disorders. However, potential new avenues for therapeutics can be tested by quantifying the rate of metabolism of exogenous dopa i...

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“…As DOPA is the precursor of the neurotransmitter dopamine, the extent of accumulation of [ 18 F]F-DOPA in the brain reflects the functional integrity of the presynaptic dopaminergic synthesis [5] and visualizes the activity of aromatic amino acid decarboxylase (AADC), which converts [ 18 F]F-DOPA to 18 F-dopamine. Likewise, the [ 18 F]F-DOPA uptake can also be relevant for determining the effects of treatment of the underlying pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

6-[¹⁸F]Fluoro-L-DOPA: A Well-Established Neurotracer with Expanding Application Spectrum and Strongly Improved Radiosyntheses

Pretze

Wängler

2014

BioMed Research International

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For many years, the main application of [18F]F-DOPA has been the PET imaging of neuropsychiatric diseases, movement disorders, and brain malignancies. Recent findings however point to very favorable results of this tracer for the imaging of other malignant diseases such as neuroendocrine tumors, pheochromocytoma, and pancreatic adenocarcinoma expanding its application spectrum. With the application of this tracer in neuroendocrine tumor imaging, improved radiosyntheses have been developed. Among these, the no-carrier-added nucleophilic introduction of fluorine-18, especially, has gained increasing attention as it gives [18F]F-DOPA in higher specific activities and shorter reaction times by less intricate synthesis protocols. The nucleophilic syntheses which were developed recently are able to provide [18F]F-DOPA by automated syntheses in very high specific activities, radiochemical yields, and enantiomeric purities. This review summarizes the developments in the field of [18F]F-DOPA syntheses using electrophilic synthesis pathways as well as recent developments of nucleophilic syntheses of [18F]F-DOPA and compares the different synthesis strategies regarding the accessibility and applicability of the products for human in vivo PET tumor imaging.

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On the Rate of Decarboxylation of Dopa to Dopamine in Living Mammalian Brain^a

Cited by 13 publications

References 129 publications

Catecholamines and cognition after traumatic brain injury

Catecholamines and cognition after traumatic brain injury

Compartmental analysis of dopa decarboxylation in living brain from dynamic positron emission tomograms

6-[¹⁸F]Fluoro-L-DOPA: A Well-Established Neurotracer with Expanding Application Spectrum and Strongly Improved Radiosyntheses

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On the Rate of Decarboxylation of Dopa to Dopamine in Living Mammalian Braina

Cited by 13 publications

References 129 publications

Catecholamines and cognition after traumatic brain injury

Catecholamines and cognition after traumatic brain injury

Compartmental analysis of dopa decarboxylation in living brain from dynamic positron emission tomograms

6-[18F]Fluoro-L-DOPA: A Well-Established Neurotracer with Expanding Application Spectrum and Strongly Improved Radiosyntheses

Contact Info

Product

Resources

About

On the Rate of Decarboxylation of Dopa to Dopamine in Living Mammalian Brain^a

6-[¹⁸F]Fluoro-L-DOPA: A Well-Established Neurotracer with Expanding Application Spectrum and Strongly Improved Radiosyntheses