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  1. 原著論文

Synthesis and characterization of 11C-labeled benzyl amidine derivatives as PET radioligands for GluN2B subunit of the NMDA receptors

https://repo.qst.go.jp/records/49349
https://repo.qst.go.jp/records/49349
f9e37d90-5e92-4e6b-8fc1-8e2330eaa9da
Item type 学術雑誌論文 / Journal Article(1)
公開日 2018-11-19
タイトル
タイトル Synthesis and characterization of 11C-labeled benzyl amidine derivatives as PET radioligands for GluN2B subunit of the NMDA receptors
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_6501
資源タイプ journal article
アクセス権
アクセス権 metadata only access
アクセス権URI http://purl.org/coar/access_right/c_14cb
著者 Fuchigami, Takeshi

× Fuchigami, Takeshi

WEKO 864945

Fuchigami, Takeshi

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Fujimoto, Noriko

× Fujimoto, Noriko

WEKO 864946

Fujimoto, Noriko

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Haradahira, Terushi

× Haradahira, Terushi

WEKO 864947

Haradahira, Terushi

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Nojiri, Yumiko

× Nojiri, Yumiko

WEKO 864948

Nojiri, Yumiko

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Okauchi, Takashi

× Okauchi, Takashi

WEKO 864949

Okauchi, Takashi

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Maeda, Jun

× Maeda, Jun

WEKO 864950

Maeda, Jun

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Suhara, Tetsuya

× Suhara, Tetsuya

WEKO 864951

Suhara, Tetsuya

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Yamamoto, Fumihiko

× Yamamoto, Fumihiko

WEKO 864952

Yamamoto, Fumihiko

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Nakayama, Morio

× Nakayama, Morio

WEKO 864953

Nakayama, Morio

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Maeda, Minoru

× Maeda, Minoru

WEKO 864954

Maeda, Minoru

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Mukai, Takahiro

× Mukai, Takahiro

WEKO 864955

Mukai, Takahiro

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Maeda, Jun

× Maeda, Jun

WEKO 864956

en Maeda, Jun

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Suhara, Tetsuya

× Suhara, Tetsuya

WEKO 864957

en Suhara, Tetsuya

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抄録
内容記述タイプ Abstract
内容記述 GluN2B-containing NMDA receptors (NMDARs) play fundamental roles in learning and memory, although they are also associated with various brain disorders. In this study, we synthesized and evaluated three 11 C-labeled N-benzyl amidine derivatives 2-[11 C]methoxybenzyl) cinnamamidine ([11 C]CBA), N-(2-[11 C]methoxybenzyl)-2- naphthamidine ([11 C]NBA) and N-(2-[11 C]methoxybenzyl)quinoline-3-carboxamidine ([11 C]QBA) as PET radioligands for these receptors. The 11 C-benzyl amidines were synthesized via conventional methylation of corresponding des-methyl precursors with [11 C]CH3 I. In vitro binding characteristics were examined in brain sagittal sections using various GluN2B modulators and off-target ligands. Further, in vivo brain distribution studies were performed in normal mice. The 11 C-labeled benzyl amidines showed high specific binding to the GluN2B subunit at in vitro. In particular, the quinoline derivative [11 C] QBA had the best binding properties in terms of high brain localization to GluN2B-rich regions and specificity to the GluN2B subunit. Conversely, these 11 C-radioligands showed the brain distributions were inconsistent with GluN2B expression in biodistribution experiments. The majority of the radiolabeled compounds were identified as metabolized forms, of which amido derivatives seemed to be the major species. Although these 11 C-ligands had high specific binding to the GluN2B subunit, significant improvement in metabolic stability is necessary for successful PET imaging of the GluN2B subunit of NMDARs.
書誌情報 Journal of Labelled Compounds and Radiopharmaceuticals

巻 61, 号 14, p. 1095-1105, 発行日 2018-11
出版者
出版者 Wiley
ISSN
収録物識別子タイプ ISSN
収録物識別子 0362-4803
PubMed番号
識別子タイプ PMID
関連識別子 30375667
DOI
識別子タイプ DOI
関連識別子 10.1002/jlcr.3691
関連サイト
識別子タイプ URI
関連識別子 https://onlinelibrary.wiley.com/doi/full/10.1002/jlcr.3691
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