Quantification of cerebral nicotinic acetylcholine receptors by PET using 2-[18F]fluoro-A-85380 and the multiinjection approach

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dc.contributor.authorGallezot, JDen_AU
dc.contributor.authorBottlaender, MAen_AU
dc.contributor.authorDelforge, Jen_AU
dc.contributor.authorValette, Hen_AU
dc.contributor.authorSaba, Wen_AU
dc.contributor.authorDollé, Fen_AU
dc.contributor.authorCoulon, CMen_AU
dc.contributor.authorOttaviani, MPen_AU
dc.contributor.authorHinnen, Fen_AU
dc.contributor.authorSyrota, Aen_AU
dc.contributor.authorGrégoire, MCen_AU
dc.date.accessioned2014-03-23T23:33:57Zen_AU
dc.date.available2014-03-23T23:33:57Zen_AU
dc.date.issued2008-01-01en_AU
dc.date.statistics2014-03-24en_AU
dc.description.abstractThe multiinjection approach was used to study in vivo interactions between α4β2* nicotinic acetylcholine receptors and 2-[18F]fluoro-A-85380 in baboons. The ligand kinetics was modeled by the usual nonlinear compartment model composed of three compartments (arterial plasma, free and specifically bound ligand in tissue). Arterial blood samples were collected to generate a metabolite-corrected plasma input function. The experimental protocol, which consisted of three injections of labeled or unlabeled ligand, was aiming at identifying all parameters in one experiment. Various parameters, including B′max (the binding sites density) and KdVR (the apparent in vivo affinity of 2-[18F]fluoro-A-85380) could then be estimated in thalamus and in several receptor-poor regions. B′max estimate was 3.0±0.3 pmol/mL in thalamus, and ranged from 0.25 to 1.58 pmol/mL in extrathalamic regions. Although KdVR could be precisely estimated, the association and dissociation rate constants kon/VR and koff could not be identified separately. A second protocol was then used to estimate koff more precisely in the thalamus. Having estimated all model parameters, we performed simulations of 2-[18F]fluoro-A-85380 kinetics to test equilibrium hypotheses underlying simplified approaches. These showed that a pseudo-equilibrium is quickly reached between the free and bound compartments, a favorable situation to apply Logan graphical analysis. In contrast, the pseudo-equilibrium between the plasma and free compartments is only reached after several hours. The ratio of radioligand concentration in these two compartments then overestimates the true equilibrium value, an unfavorable situation to estimate distribution volumes from late images after a bolus injection. © 2008, Nature Publishing Group.en_AU
dc.identifier.citationGallezot, J. D., Bottlaender, M. A., Delforge, J., Valette, H., Saba, W., Dolle, F., Coulon, C. M., Ottaviani, M. P., Hinnen, F., Syrota, A. & Grégoire, M. C. (2008). Quantification of cerebral nicotinic acetylcholine receptors by PET using 2-[18F]fluoro-A-85380 and the multiinjection approach. Journal of Cerebral Blood Flow & Metabolism, 28, 172-189. doi:10.1038/sj.jcbfm.9600505en_AU
dc.identifier.govdoc4532en_AU
dc.identifier.issn0271-678Xen_AU
dc.identifier.journaltitleJournal of Cerebral Blood Flow & Metabolismen_AU
dc.identifier.pagination172-189en_AU
dc.identifier.urihttp://dx.doi.org/10.1038/sj.jcbfm.9600505en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/5277en_AU
dc.identifier.volume28en_AU
dc.language.isoenen_AU
dc.publisherNature Publishing Groupen_AU
dc.subjectCompartmentsen_AU
dc.subjectAcetylcholineen_AU
dc.subjectPositron computed tomographyen_AU
dc.subjectReceptorsen_AU
dc.subjectLigandsen_AU
dc.subjectRatsen_AU
dc.titleQuantification of cerebral nicotinic acetylcholine receptors by PET using 2-[18F]fluoro-A-85380 and the multiinjection approachen_AU
dc.typeJournal Articleen_AU
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