Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Acta Neurologica Scandinavica |
| Vol/bind | 110 |
| Udgave nummer | 3 |
| Sider (fra-til) | 188-95 |
| Antal sider | 7 |
| ISSN | 0001-6314 |
| DOI | |
| Status | Udgivet - 2004 |
| Udgivet eksternt | Ja |
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I: Acta Neurologica Scandinavica, Bind 110, Nr. 3, 2004, s. 188-95.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Levodopa effect on [18F]fluorodopa influx to brain: normal volunteers and patients with Parkinson's disease.
AU - Kumakura, Y
AU - Danielsen, E H
AU - Reilhac, A
AU - Gjedde, A
AU - Cumming, P
PY - 2004
Y1 - 2004
N2 - 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 [(18)F]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 [(18)F]fluorodopa in cerebellum (, ml/g) of both patients and control subjects, without significantly altering the unidirectional blood-brain clearance (, ml/g/min) or the relative activity of DOPA decarboxylase (, min(-1)) in putamen. CONCLUSION: We conclude that levodopa treatment increases the distribution volume of [(18)F]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.
AB - 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 [(18)F]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 [(18)F]fluorodopa in cerebellum (, ml/g) of both patients and control subjects, without significantly altering the unidirectional blood-brain clearance (, ml/g/min) or the relative activity of DOPA decarboxylase (, min(-1)) in putamen. CONCLUSION: We conclude that levodopa treatment increases the distribution volume of [(18)F]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.
U2 - 10.1111/j.1600-0404.2004.00299.x
DO - 10.1111/j.1600-0404.2004.00299.x
M3 - Journal article
C2 - 15285777
SN - 0001-6314
VL - 110
SP - 188
EP - 195
JO - Acta Neurologica Scandinavica
JF - Acta Neurologica Scandinavica
IS - 3
ER -