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Preclinical and the first clinical studies on [(11)C]ITMM for mapping metabotropic glutamate receptor subtype 1 by positron emission tomography.
https://repo.qst.go.jp/records/46526
https://repo.qst.go.jp/records/46526a5857f47-52f6-4482-9529-629edce7ac92
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2013-04-12 | |||||
| タイトル | ||||||
| タイトル | Preclinical and the first clinical studies on [(11)C]ITMM for mapping metabotropic glutamate receptor subtype 1 by positron emission tomography. | |||||
| 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 |
Toyohara, Jun
× Toyohara, Jun× Sakata, Muneyuki× Fujinaga, Masayuki× Yamasaki, Tomoteru× Oda, Keiichi× Ishii, Kenji× Zhang, Ming-Rong× Ishiwata, Kiichi× 豊原 潤× 藤永 雅之× 山崎 友照× 張 明栄 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Introduction Preclinical studies and first positron emission tomography (PET) imaging studies were performed using N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-[11C]methoxy-N-methylbenzamide ([11C]ITMM) to map metabotropic glutamate receptor type 1 (mGluR1) in the human brain. Methods [11C]ITMM was synthesized by O-methylation of the desmethyl precursor with [11C]methyl triflate in the presence of NaOH at room temperature. In vitro selectivity and brain distributions of [11C]ITMM in mice were characterized. Radiation absorbed-dose by [11C]ITMM in humans was calculated from mouse distribution data. Acute toxicity of ITMM at 4.72mg/kg body weight (>74,000-fold clinical equivalent dose of [11C]ITMM) was evaluated. Mutagenicity of ITMM was studied by the Ames test. Clinical PET imaging of mGluR1 with [11C] ITMM was performed in a healthy volunteer. Results ITMM had low activity for a 28-standard receptor binding profile. Regional brain uptake of [11C]ITMM in mice was heterogeneous and consistent with known mGluR1 distributions. The radiation absorbed-dose by [11C]ITMM in humans was sufficiently low for clinical use, and no acute toxicity or mutagenicity of ITMM occurred. A 90-min dynamic PET scan with [11C]ITMM in a healthy volunteer showed a gradual increase of radioactivity in the cerebellum. Total distribution volume of [11C]ITMM was highest in the cerebellum, followed by thalamus, cerebral cortex, and striatum; regional differences in brain radioactivity corresponded to the mGluR1 distribution in the brain. Peripherally, [11C]ITMM was stable in humans: 60% of the plasma radioactivity remained in the unchanged form for 60min. Conclusions [11C] ITMM is a suitable radioligand for imaging mGluR1 in the human brain providing acceptable dosimetry and pharmacological safety at the dose required for PET. |
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| 書誌情報 |
Nuclear Medicine and Biology 巻 40, 号 2, p. 214-220, 発行日 2012-12 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0969-8051 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.nucmedbio.2012.11.008 | |||||
