Levodopa effect on [18F]fluorodopa influx to brain: Normal volunteers and patients with Parkinson's disease

Y. Kumakura, E. H. Danielsen, A. Reilhac, A. Gjedde, P. Cumming

Research output: Contribution to journalArticle

Abstract

Objectives - Levodopa is the immediate precursor of dopamine and the substrate for DOPA decarboxylase, an enzyme subject to regulation in living brain. To test whether this regulation changes in disease, we used Positron Emission Tomography (PET) with parametric mapping to measure the effect of levodopa on the net clearance of [18F]fluorodopa to brain (K, ml/g/min). Methods - Five patients with early Parkinson's disease with pause of medication for 3 days and six age-matched healthy volunteers were studied in a baseline condition and after levodopa challenge. Results - Levodopa (200 mg as Sinemet) increased the magnitude of the net clearance K in the left and right putamen of the healthy volunteers by 11 % relative to the baseline condition. In contrast, resumption of medication with levodopa did not significantly alter the magnitude of K in putamen of the Parkinson's disease patients. Compartmental analysis was used to probe the physiological basis of the activation of K: levodopa treatment increased by 15% the apparent distribution volume of [ 18F]fluorodopa in cerebellum (VeD, ml/g) of both patients and control subjects, without significantly altering the unidirectional blood-brain clearance (K1D, ml/g/min) or the relative activity of DOPA decarboxylase (k3D, min -1) in putamen. Conclusion - We conclude that levodopa treatment increases the distribution volume of [18F]fluorodopa in brain, increasing its availability for utilization in dopamine terminals. We speculate that levodopa act as a direct beta-adrenergic agonist at receptors regulating the permeability of the blood-brain barrier to levodopa. However, the PET analytical method was without sufficient power to detect the consequent increase in magnitude of K in brain of only five Parkinson's disease subjects.

Original languageEnglish (US)
Pages (from-to)188-195
Number of pages8
JournalActa Neurologica Scandinavica
Volume110
Issue number3
DOIs
StatePublished - Sep 2004
Externally publishedYes

Fingerprint

Levodopa
Parkinson Disease
Healthy Volunteers
Brain
Putamen
Carboxy-Lyases
Positron-Emission Tomography
Dopamine
fluorodopa F 18
Adrenergic beta-Agonists
Blood-Brain Barrier
Cerebellum
Permeability
Enzymes
Therapeutics

Keywords

  • [F]fluorodopa
  • Compartmental analysis
  • Levodopa
  • Paridnson's disease
  • Positron emission tomography

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Levodopa effect on [18F]fluorodopa influx to brain : Normal volunteers and patients with Parkinson's disease. / Kumakura, Y.; Danielsen, E. H.; Reilhac, A.; Gjedde, A.; Cumming, P.

In: Acta Neurologica Scandinavica, Vol. 110, No. 3, 09.2004, p. 188-195.

Research output: Contribution to journalArticle

Kumakura, Y. ; Danielsen, E. H. ; Reilhac, A. ; Gjedde, A. ; Cumming, P. / Levodopa effect on [18F]fluorodopa influx to brain : Normal volunteers and patients with Parkinson's disease. In: Acta Neurologica Scandinavica. 2004 ; Vol. 110, No. 3. pp. 188-195.
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