Pharmacological treatment with L-DOPA may reduce striatal dopamine transporter binding in in vivo imaging studies

S. Nikolaus; C. Antke; H. Hautzel; H.-W. Mueller

doi:10.3413/Nukmed-0764-15-08

Nuklearmedizin - NuclearMedicine, Inhaltsverzeichnis

Nuklearmedizin 2016; 55(01): 21-28
DOI: 10.3413/Nukmed-0764-15-08

Review

Schattauer GmbH

Pharmacological treatment with L-DOPA may reduce striatal dopamine transporter binding in in vivo imaging studies

Pharmakologische Behandlung mit L-DOPA kann die striatale Dopamintransporterbindung in In-vivo- Bildgebungsstudien reduzieren

S. Nikolaus

¹Clinic of Nuclear Medicine, University Hospital Düsseldorf, Germany

,

C. Antke

¹Clinic of Nuclear Medicine, University Hospital Düsseldorf, Germany

,

H. Hautzel

¹Clinic of Nuclear Medicine, University Hospital Düsseldorf, Germany

,

H.-W. Mueller

¹Clinic of Nuclear Medicine, University Hospital Düsseldorf, Germany

› Institutsangaben

Abstract

Summary

Numerous neurologic and psychiatric conditions are treated with pharmacological compounds, which lead to an increase of synaptic dopamine (DA) levels. One example is the DA precursor L-3,4-dihydroxyphenylalanine (L-DOPA), which is converted to DA in the presynaptic terminal. If the increase of DA concentrations in the synaptic cleft leads to competition with exogenous radioligands for presynaptic binding sites, this may have implications for DA transporter (DAT) imaging studies in patients under DAergic medication.

This paper gives an overview on those findings, which, so far, have been obtained on DAT binding in human Parkinson’s disease after treatment with L-DOPA. Findings, moreover, are related to results obtained on rats, mice or non-human primates. Results indicate that DAT imaging may be reduced in the striata of healthy animals, in the unlesioned striata of animal models of unilateral Parkinson’s disease and in less severly impaired striata of Parkinsonian patients, if animal or human subjects are under acute or subchronic treatment with L-DOPA. If also striatal DAT binding is susceptible to alterations of synaptic DA levels, this may allow to quantify DA reuptake in analogy to DA release by assessing the competition between endogenous DA and the administered exogenous DAT radioligand.

Zusammenfassung

Viele neurologische und psychiatrische Erkrankungen werden mit Medikamenten behandelt, die die synaptischen Dopamin(DA)-Konzentration erhöhen. Ein Beispiel ist das DA-Vorläufermolekül L-3,4-Dihydroxyphenyl alanin (L-DOPA), das in der präsynaptischen Endigung zu DA umgesetzt wird. Falls der Anstieg der synaptischen DA-Konzentration zu einer Kompetiton mit exogenen Radioliganden um die präsynaptischen Bindungsstellen führt, kann dies Implikationen für die Dopamintransporter(DAT)-Bildgebung bei Patienten unter DAerger Medikation haben.

Diese Arbeit gibt einen Überblick über die DAT-Befunde, die bislang an Parkinson-Patienten nach Behandlung mit L-DOPA vorliegen. Diese Resultate werden in Beziehung zu den Befunden an Mäusen, Ratten und nichthumanen Primaten gesetzt. Die Ergebnisse zeigen, dass die DAT-Bindung in den Striata gesunder Tiere, in den unlädierten Striata von Hemiparkinsonmodellen und in den weniger schwer geschädigten Striata von Parkinson-patienten reduziert sein kann, wenn Menschen oder Tiere unter akuter oder subchronischer Behandlung mit L-DOPA stehen. Falls die striatale DAT-Bindung für Änderungen der synaptischen DA-Konzentrationen empfindlich ist, erlaubt dies die Quantifizierung der DA-Wiederaufnahme in Analogie zur DA-Freisetzung durch die Messung der Kompetittion zwischen endogenem DA und dem verabreichten exogenen DAT-Radioliganden.

Keywords

Dopamine - L-DOPA - dopamine transporter - dopamine reuptake - Parkinson’s disease

Schlüsselwörter

Dopamin - L-DOPA - Dopamintransporter - Dopamin- Wiederaufnahme - M. Parkinson

Volltext

Referenzen

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