Dopamine transporter binding is unaffected by L-DOPA administration in normal and MPTP-treated monkeys.

<h4>Background</h4>Radiotracer imaging of the presynaptic nigrostriatal dopaminergic system is used to assess disease progression in Parkinson's disease (PD) and may provide a useful adjunct to clinical assessment during therapeutic trials of potential neuroprotective agents. Severa...

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Autores principales:	Pierre-Olivier Fernagut, Qin Li, Sandra Dovero, Piu Chan, Tao Wu, Paula Ravenscroft, Michael Hill, Zhenwen Chen, Erwan Bezard
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ffb09a1705c5481e978752dcd7fed588
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spelling	oai:doaj.org-article:ffb09a1705c5481e978752dcd7fed5882021-11-18T07:36:39ZDopamine transporter binding is unaffected by L-DOPA administration in normal and MPTP-treated monkeys.1932-620310.1371/journal.pone.0014053https://doaj.org/article/ffb09a1705c5481e978752dcd7fed5882010-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21124922/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Radiotracer imaging of the presynaptic nigrostriatal dopaminergic system is used to assess disease progression in Parkinson's disease (PD) and may provide a useful adjunct to clinical assessment during therapeutic trials of potential neuroprotective agents. Several clinical trials comparing dopamine agonists to L-DOPA or early vs. late L-DOPA have revealed differences between clinical assessment and imaging of the presynaptic dopaminergic system, hence questioning the comparability of these measures as neuroprotection outcome variables. Thus, results of these studies may have been affected by factors other than the primary biological process investigated.<h4>Methodology/principal findings</h4>We tested the possibility that L-DOPA might interfere with DAT binding. Post-mortem DAT binding was conducted in normal and MPTP-treated macaque monkeys that were administered L-DOPA, acutely or chronically. In parallel, DAT SPECT was conducted in MPTP-treated animals that were administered chronic L-DOPA. [99mTc]TRODAT-1 SPECT binding was similarly reduced in all MPTP monkeys regardless of L-DOPA treatment. L-DOPA had no significant effect on post-mortem DAT binding either in saline or in MPTP-lesioned animals.<h4>Conclusions/significance</h4>These data indicate that L-DOPA does not induce modifications of DAT expression detectable by SPECT of by DAT binding autoradiography, suggesting that differences between clinical assessment and radiotracer imaging in clinical trials may not be specifically related to L-DOPA treatment.Pierre-Olivier FernagutQin LiSandra DoveroPiu ChanTao WuPaula RavenscroftMichael HillZhenwen ChenErwan BezardPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 11, p e14053 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pierre-Olivier Fernagut Qin Li Sandra Dovero Piu Chan Tao Wu Paula Ravenscroft Michael Hill Zhenwen Chen Erwan Bezard Dopamine transporter binding is unaffected by L-DOPA administration in normal and MPTP-treated monkeys.
description	<h4>Background</h4>Radiotracer imaging of the presynaptic nigrostriatal dopaminergic system is used to assess disease progression in Parkinson's disease (PD) and may provide a useful adjunct to clinical assessment during therapeutic trials of potential neuroprotective agents. Several clinical trials comparing dopamine agonists to L-DOPA or early vs. late L-DOPA have revealed differences between clinical assessment and imaging of the presynaptic dopaminergic system, hence questioning the comparability of these measures as neuroprotection outcome variables. Thus, results of these studies may have been affected by factors other than the primary biological process investigated.<h4>Methodology/principal findings</h4>We tested the possibility that L-DOPA might interfere with DAT binding. Post-mortem DAT binding was conducted in normal and MPTP-treated macaque monkeys that were administered L-DOPA, acutely or chronically. In parallel, DAT SPECT was conducted in MPTP-treated animals that were administered chronic L-DOPA. [99mTc]TRODAT-1 SPECT binding was similarly reduced in all MPTP monkeys regardless of L-DOPA treatment. L-DOPA had no significant effect on post-mortem DAT binding either in saline or in MPTP-lesioned animals.<h4>Conclusions/significance</h4>These data indicate that L-DOPA does not induce modifications of DAT expression detectable by SPECT of by DAT binding autoradiography, suggesting that differences between clinical assessment and radiotracer imaging in clinical trials may not be specifically related to L-DOPA treatment.
format	article
author	Pierre-Olivier Fernagut Qin Li Sandra Dovero Piu Chan Tao Wu Paula Ravenscroft Michael Hill Zhenwen Chen Erwan Bezard
author_facet	Pierre-Olivier Fernagut Qin Li Sandra Dovero Piu Chan Tao Wu Paula Ravenscroft Michael Hill Zhenwen Chen Erwan Bezard
author_sort	Pierre-Olivier Fernagut
title	Dopamine transporter binding is unaffected by L-DOPA administration in normal and MPTP-treated monkeys.
title_short	Dopamine transporter binding is unaffected by L-DOPA administration in normal and MPTP-treated monkeys.
title_full	Dopamine transporter binding is unaffected by L-DOPA administration in normal and MPTP-treated monkeys.
title_fullStr	Dopamine transporter binding is unaffected by L-DOPA administration in normal and MPTP-treated monkeys.
title_full_unstemmed	Dopamine transporter binding is unaffected by L-DOPA administration in normal and MPTP-treated monkeys.
title_sort	dopamine transporter binding is unaffected by l-dopa administration in normal and mptp-treated monkeys.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/ffb09a1705c5481e978752dcd7fed588
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Dopamine transporter binding is unaffected by L-DOPA administration in normal and MPTP-treated monkeys.

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