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Radioligand binding analysis of α(2) adrenoceptors with [(11)C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding
We describe a novel method of kinetic analysis of radioligand binding to neuroreceptors in brain in vivo, here applied to noradrenaline receptors in rat brain. The method uses positron emission tomography (PET) of [(11)C]yohimbine binding in brain to quantify the density and affinity of α(2) adrenoc...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700124/ https://www.ncbi.nlm.nih.gov/pubmed/29167492 http://dx.doi.org/10.1038/s41598-017-16020-1 |
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author | Phan, Jenny-Ann Landau, Anne M. Jakobsen, Steen Wong, Dean F. Gjedde, Albert |
author_facet | Phan, Jenny-Ann Landau, Anne M. Jakobsen, Steen Wong, Dean F. Gjedde, Albert |
author_sort | Phan, Jenny-Ann |
collection | PubMed |
description | We describe a novel method of kinetic analysis of radioligand binding to neuroreceptors in brain in vivo, here applied to noradrenaline receptors in rat brain. The method uses positron emission tomography (PET) of [(11)C]yohimbine binding in brain to quantify the density and affinity of α(2) adrenoceptors under condition of changing radioligand binding to plasma proteins. We obtained dynamic PET recordings from brain of Spraque Dawley rats at baseline, followed by pharmacological challenge with unlabeled yohimbine (0.3 mg/kg). The challenge with unlabeled ligand failed to diminish radioligand accumulation in brain tissue, due to the blocking of radioligand binding to plasma proteins that elevated the free fractions of the radioligand in plasma. We devised a method that graphically resolved the masking of unlabeled ligand binding by the increase of radioligand free fractions in plasma. The Extended Inhibition Plot introduced here yielded an estimate of the volume of distribution of non-displaceable ligand in brain tissue that increased with the increase of the free fraction of the radioligand in plasma. The resulting binding potentials of the radioligand declined by 50–60% in the presence of unlabeled ligand. The kinetic unmasking of inhibited binding reflected in the increase of the reference volume of distribution yielded estimates of receptor saturation consistent with the binding of unlabeled ligand. |
format | Online Article Text |
id | pubmed-5700124 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57001242017-11-30 Radioligand binding analysis of α(2) adrenoceptors with [(11)C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding Phan, Jenny-Ann Landau, Anne M. Jakobsen, Steen Wong, Dean F. Gjedde, Albert Sci Rep Article We describe a novel method of kinetic analysis of radioligand binding to neuroreceptors in brain in vivo, here applied to noradrenaline receptors in rat brain. The method uses positron emission tomography (PET) of [(11)C]yohimbine binding in brain to quantify the density and affinity of α(2) adrenoceptors under condition of changing radioligand binding to plasma proteins. We obtained dynamic PET recordings from brain of Spraque Dawley rats at baseline, followed by pharmacological challenge with unlabeled yohimbine (0.3 mg/kg). The challenge with unlabeled ligand failed to diminish radioligand accumulation in brain tissue, due to the blocking of radioligand binding to plasma proteins that elevated the free fractions of the radioligand in plasma. We devised a method that graphically resolved the masking of unlabeled ligand binding by the increase of radioligand free fractions in plasma. The Extended Inhibition Plot introduced here yielded an estimate of the volume of distribution of non-displaceable ligand in brain tissue that increased with the increase of the free fraction of the radioligand in plasma. The resulting binding potentials of the radioligand declined by 50–60% in the presence of unlabeled ligand. The kinetic unmasking of inhibited binding reflected in the increase of the reference volume of distribution yielded estimates of receptor saturation consistent with the binding of unlabeled ligand. Nature Publishing Group UK 2017-11-22 /pmc/articles/PMC5700124/ /pubmed/29167492 http://dx.doi.org/10.1038/s41598-017-16020-1 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Phan, Jenny-Ann Landau, Anne M. Jakobsen, Steen Wong, Dean F. Gjedde, Albert Radioligand binding analysis of α(2) adrenoceptors with [(11)C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding |
title | Radioligand binding analysis of α(2) adrenoceptors with [(11)C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding |
title_full | Radioligand binding analysis of α(2) adrenoceptors with [(11)C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding |
title_fullStr | Radioligand binding analysis of α(2) adrenoceptors with [(11)C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding |
title_full_unstemmed | Radioligand binding analysis of α(2) adrenoceptors with [(11)C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding |
title_short | Radioligand binding analysis of α(2) adrenoceptors with [(11)C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding |
title_sort | radioligand binding analysis of α(2) adrenoceptors with [(11)c]yohimbine in brain in vivo: extended inhibition plot correction for plasma protein binding |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700124/ https://www.ncbi.nlm.nih.gov/pubmed/29167492 http://dx.doi.org/10.1038/s41598-017-16020-1 |
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