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In Vivo Evaluation of α7 Nicotinic Acetylcholine Receptor Agonists [(11)C]A-582941 and [(11)C]A-844606 in Mice and Conscious Monkeys
BACKGROUND: The α7 nicotinic acetylcholine receptors (nAChRs) play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. The goal of this study was to evaluate the two carbon-11-labeled α7 nAChR agonists [(11)C]A-582941 and [(11)C]A...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813863/ https://www.ncbi.nlm.nih.gov/pubmed/20126539 http://dx.doi.org/10.1371/journal.pone.0008961 |
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author | Toyohara, Jun Ishiwata, Kiichi Sakata, Muneyuki Wu, Jin Nishiyama, Shingo Tsukada, Hideo Hashimoto, Kenji |
author_facet | Toyohara, Jun Ishiwata, Kiichi Sakata, Muneyuki Wu, Jin Nishiyama, Shingo Tsukada, Hideo Hashimoto, Kenji |
author_sort | Toyohara, Jun |
collection | PubMed |
description | BACKGROUND: The α7 nicotinic acetylcholine receptors (nAChRs) play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. The goal of this study was to evaluate the two carbon-11-labeled α7 nAChR agonists [(11)C]A-582941 and [(11)C]A-844606 for their potential as novel positron emission tomography (PET) tracers. METHODOLOGY/PRINCIPAL FINDINGS: The two tracers were synthesized by methylation of the corresponding desmethyl precursors using [(11)C]methyl triflate. Effects of receptor blockade in mice were determined by coinjection of either tracer along with a carrier or an excess amount of a selective α7 nAChR agonist (SSR180711). Metabolic stability was investigated using radio-HPLC. Dynamic PET scans were performed in conscious monkeys with/without SSR180711-treatment. [(11)C]A-582941 and [(11)C]A-844606 showed high uptake in the mouse brain. Most radioactive compounds in the brain were detected as an unchanged form. However, regional selectivity and selective receptor blockade were not clearly observed for either compound in the mouse brain. On the other hand, the total distribution volume of [(11)C]A-582941 and [(11)C]A-844606 was high in the hippocampus and thalamus but low in the cerebellum in the conscious monkey brain, and reduced by pretreatment with SSR180711. CONCLUSIONS/SIGNIFICANCE: A nonhuman primate study suggests that [(11)C]A-582941 and [(11)C]A-844606 would be potential PET ligands for imaging α7 nAChRs in the human brain. |
format | Text |
id | pubmed-2813863 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-28138632010-02-02 In Vivo Evaluation of α7 Nicotinic Acetylcholine Receptor Agonists [(11)C]A-582941 and [(11)C]A-844606 in Mice and Conscious Monkeys Toyohara, Jun Ishiwata, Kiichi Sakata, Muneyuki Wu, Jin Nishiyama, Shingo Tsukada, Hideo Hashimoto, Kenji PLoS One Research Article BACKGROUND: The α7 nicotinic acetylcholine receptors (nAChRs) play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. The goal of this study was to evaluate the two carbon-11-labeled α7 nAChR agonists [(11)C]A-582941 and [(11)C]A-844606 for their potential as novel positron emission tomography (PET) tracers. METHODOLOGY/PRINCIPAL FINDINGS: The two tracers were synthesized by methylation of the corresponding desmethyl precursors using [(11)C]methyl triflate. Effects of receptor blockade in mice were determined by coinjection of either tracer along with a carrier or an excess amount of a selective α7 nAChR agonist (SSR180711). Metabolic stability was investigated using radio-HPLC. Dynamic PET scans were performed in conscious monkeys with/without SSR180711-treatment. [(11)C]A-582941 and [(11)C]A-844606 showed high uptake in the mouse brain. Most radioactive compounds in the brain were detected as an unchanged form. However, regional selectivity and selective receptor blockade were not clearly observed for either compound in the mouse brain. On the other hand, the total distribution volume of [(11)C]A-582941 and [(11)C]A-844606 was high in the hippocampus and thalamus but low in the cerebellum in the conscious monkey brain, and reduced by pretreatment with SSR180711. CONCLUSIONS/SIGNIFICANCE: A nonhuman primate study suggests that [(11)C]A-582941 and [(11)C]A-844606 would be potential PET ligands for imaging α7 nAChRs in the human brain. Public Library of Science 2010-02-01 /pmc/articles/PMC2813863/ /pubmed/20126539 http://dx.doi.org/10.1371/journal.pone.0008961 Text en Toyohara et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Toyohara, Jun Ishiwata, Kiichi Sakata, Muneyuki Wu, Jin Nishiyama, Shingo Tsukada, Hideo Hashimoto, Kenji In Vivo Evaluation of α7 Nicotinic Acetylcholine Receptor Agonists [(11)C]A-582941 and [(11)C]A-844606 in Mice and Conscious Monkeys |
title |
In Vivo Evaluation of α7 Nicotinic Acetylcholine Receptor Agonists [(11)C]A-582941 and [(11)C]A-844606 in Mice and Conscious Monkeys |
title_full |
In Vivo Evaluation of α7 Nicotinic Acetylcholine Receptor Agonists [(11)C]A-582941 and [(11)C]A-844606 in Mice and Conscious Monkeys |
title_fullStr |
In Vivo Evaluation of α7 Nicotinic Acetylcholine Receptor Agonists [(11)C]A-582941 and [(11)C]A-844606 in Mice and Conscious Monkeys |
title_full_unstemmed |
In Vivo Evaluation of α7 Nicotinic Acetylcholine Receptor Agonists [(11)C]A-582941 and [(11)C]A-844606 in Mice and Conscious Monkeys |
title_short |
In Vivo Evaluation of α7 Nicotinic Acetylcholine Receptor Agonists [(11)C]A-582941 and [(11)C]A-844606 in Mice and Conscious Monkeys |
title_sort | in vivo evaluation of α7 nicotinic acetylcholine receptor agonists [(11)c]a-582941 and [(11)c]a-844606 in mice and conscious monkeys |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813863/ https://www.ncbi.nlm.nih.gov/pubmed/20126539 http://dx.doi.org/10.1371/journal.pone.0008961 |
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