Positron emission tomography imaging demonstrates correlation between behavioral recovery and correction of dopamine neurotransmission after gene therapy.

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dc.contributor.authorLeriche, Len_AU
dc.contributor.authorBjorklund, Ten_AU
dc.contributor.authorBreysse, Nen_AU
dc.contributor.authorBesret, Len_AU
dc.contributor.authorGrégoire, MCen_AU
dc.contributor.authorCarlsson, Ten_AU
dc.contributor.authorDollé, Fen_AU
dc.contributor.authorMandel, RJen_AU
dc.contributor.authorDéglon, Nen_AU
dc.contributor.authorHantraye, Pen_AU
dc.contributor.authorKirik, Den_AU
dc.date.accessioned2010-04-06T23:56:40Zen_AU
dc.date.accessioned2010-04-30T05:07:54Zen_AU
dc.date.available2010-04-06T23:56:40Zen_AU
dc.date.available2010-04-30T05:07:54Zen_AU
dc.date.issued2009-02-04en_AU
dc.date.statistics2009-02-04en_AU
dc.description.abstractIn vivo gene transfer using viral vectors is an emerging therapy for neurodegenerative diseases with a clinical impact recently demonstrated in Parkinson's disease patients. Recombinant adeno-associated viral (rAAV) vectors, in particular, provide an excellent tool for long-term expression of therapeutic genes in the brain. Here we used the [11C]raclopride [(S)-(–)-3,5-dichloro-N-((1-ethyl-2-pyrrolidinyl)methyl)-2-hydroxy-6-methoxybenzamide] micro-positron emission tomography (PET) technique to demonstrate that delivery of the tyrosine hydroxylase (TH) and GTP cyclohydrolase 1 (GCH1) enzymes using an rAAV5 vector normalizes the increased [11C]raclopride binding in hemiparkinsonian rats. Importantly, we show in vivo by microPET imaging and postmortem by classical binding assays performed in the very same animals that the changes in [11C]raclopride after viral vector-based enzyme replacement therapy is attributable to a decrease in the affinity of the tracer binding to the D2 receptors, providing evidence for reconstitution of a functional pool of endogenous dopamine in the striatum. Moreover, the extent of the normalization in this non-invasive imaging measure was highly correlated with the functional recovery in motor behavior. The PET imaging protocol used in this study is fully adaptable to humans and thus can serve as an in vivo imaging technique to follow TH + GCH1 gene therapy in PD patients and provide an additional objective measure to a potential clinical trial using rAAV vectors to deliver L-3,4-dihydroxyphenylanaline in the brain. © 2009, Society for Neuroscienceen_AU
dc.identifier.citationLeriche, L., Bjorklund, T., Breysse, N., Besret, L.,Grégoire , M. C., Carlsson, T., Dollé, F., Mandel, R. J., Déglon, N., Hantrayne, P., & Kirik, D. (2009). Positron emission tomography imaging demonstrates correlation between behavioral recovery and correction of dopamine neurotransmission after gene therapy. Journal of Neuroscience, 29(5), 1544-1553. doi:10.1523/JNEUROSCI.4491-08.2009en_AU
dc.identifier.govdoc1508en_AU
dc.identifier.issn0270-6474en_AU
dc.identifier.issue5en_AU
dc.identifier.journaltitleJournal of Neuroscienceen_AU
dc.identifier.pagination1544-1553en_AU
dc.identifier.urihttp://dx.doi.org/10.1523/JNEUROSCI.4491-08.2009en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/3071en_AU
dc.identifier.volume29en_AU
dc.language.isoenen_AU
dc.publisherSociety for Neuroscienceen_AU
dc.subjectPositron computed tomographyen_AU
dc.subjectDopamineen_AU
dc.subjectGene therapyen_AU
dc.subjectDiseasesen_AU
dc.subjectSimulationen_AU
dc.subjectCorrelationsen_AU
dc.titlePositron emission tomography imaging demonstrates correlation between behavioral recovery and correction of dopamine neurotransmission after gene therapy.en_AU
dc.typeJournal Articleen_AU
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