『徳島大学 教育・研究者情報データベース (EDB)』---[学外] /
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EID=394411EID:394411, Map:0, LastModified:2023年5月10日(水) 19:46:57, Operator:[大家 隆弘], Avail:TRUE, Censor:承認済, Owner:[田原 強], Read:継承, Write:継承, Delete:継承.
○種別 (必須): □学術論文 (審査論文) [継承]
○言語 (必須): □英語 [継承]
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○著者 (必須): 1.田原 強 ([徳島大学.先端研究推進センター.バイオイメージング研究部門])
○役割 (任意): □責任著者 [継承]
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2. (英) Takatani Shuhei (日) (読)
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3. (英) Tsuji Mieko (日) (読)
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4. (英) Shibata Nina (日) (読)
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5. (英) Hosaka Nami (日) (読)
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6. (英) Inoue Michiko (日) (読)
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7. (英) Ohno Masahiro (日) (読)
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8. (英) Ozaki Daiki (日) (読)
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9. (英) Mawatari Aya (日) (読)
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10. (英) Watanabe Yasuyoshi (日) (読)
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11. (英) Doi Hisashi (日) (読)
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12. (英) Onoe Hirotaka (日) (読)
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○題名 (必須): □(英) Characteristic Evaluation of a 11C-Labeled Leucine Analog, l-α-[5-11C]methylleucine, as a Tracer for Brain Tumor Imaging by Positron Emission Tomography  (日)    [継承]
○副題 (任意):
○要約 (任意): □(英) Amino acid transporters are upregulated in many cancer cells, and system L amino acid transporters (LAT1-4), in particular, LAT1, which preferentially transports large, neutral, and branched side-chain amino acids, are considered a primary target for cancer positron emission tomography (PET) tracer development. Recently, we developed a C-labeled leucine analog, l-α-[5-C]methylleucine ([5-C]MeLeu), via a continuous two-step reaction of Pd-mediated C-methylation and microfluidic hydrogenation. In this study, we evaluated the characteristics of [5-C]MeLeu and also compared the sensitivity to brain tumors and inflammation with l-[C]methionine ([C]Met) to determine its potential for brain tumor imaging. Competitive inhibition experiments, protein incorporation, and cytotoxicity experiments of [5-C]MeLeu were performed in vitro. Further, metabolic analyses of [5-C]MeLeu were performed using a thin-layer chromatogram. The accumulation of [5-C]MeLeu in tumor and inflamed regions of the brain was compared with [C]Met and C-labeled ()-ketoprofen methyl ester by PET imaging, respectively. Transporter assay with various inhibitors revealed that [5-C]MeLeu is mainly transported via system L amino acid transporters, especially LAT1, into A431 cells. The protein incorporation assay and metabolic assay in vivo demonstrated that [5-C]MeLeu was neither used for protein synthesis nor metabolized. These results indicate that MeLeu is very stable in vivo. Furthermore, the treatment of A431 cells with various concentrations of MeLeu did not change their viability, even at high concentrations (∼10 mM). In brain tumors, the tumor-to-normal ratio of [5-C]MeLeu was more elevated than that of [C]Met. However, the accumulation levels of [5-C]MeLeu were lower than those of [C]Met (the standardized uptake value (SUV) of [5-C]MeLeu and [C]Met was 0.48 ± 0.08 and 0.63 ± 0.06, respectively). In brain inflammation, no significant accumulation of [5-C]MeLeu was observed at the inflamed brain area. These data suggested that [5-C]MeLeu was identified as a stable and safe agent for PET tracers and could help detect brain tumors, which overexpress the LAT1 transporter.  (日)    [継承]
○キーワード (推奨): 1. (英) Humans (日) (読) [継承]
2. (英) Leucine (日) (読) [継承]
3. (英) Positron-Emission Tomography (日) (読) [継承]
4. (英) Brain Neoplasms (日) (読) [継承]
5. (英) Radiopharmaceuticals (日) (読) [継承]
6. (英) Proteins (日) (読) [継承]
7. (英) Cell Line, Tumor (日) (読) [継承]
○発行所 (推奨):
○誌名 (必須): □Molecular Pharmaceutics ([アメリカ化学会])
(pISSN: 1543-8384, eISSN: 1543-8392)

○ISSN (任意): □1543-8392
ISSN: 1543-8384 (pISSN: 1543-8384, eISSN: 1543-8392)
Title: Molecular pharmaceutics
Title(ISO): Mol Pharm
Publisher: American Chemical Society
 (NLM Catalog)   (Scopus)   (CrossRef)  (Scopus information is found. [need login])
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○巻 (必須): □20 [継承]
○号 (必須): □3 [継承]
○頁 (必須): □1842 1849 [継承]
○都市 (任意):
○年月日 (必須): □西暦 2023年 3月 6日 (令和 5年 3月 6日) [継承]
○URL (任意):
○DOI (任意): □10.1021/acs.molpharmaceut.2c01069    (→Scopusで検索) [継承]
○PMID (任意): □36802622    (→Scopusで検索) [継承]
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○備考 (任意): 1.(英) Article.ELocationID: 10.1021/acs.molpharmaceut.2c01069  (日)    [継承]
2.(英) Article.PublicationTypeList.PublicationType: Journal Article  (日)    [継承]
3.(英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't  (日)    [継承]
4.(英) KeywordList.Keyword: [5-11C]MeLeu  (日)    [継承]
5.(英) KeywordList.Keyword: brain tumor  (日)    [継承]
6.(英) KeywordList.Keyword: leucine analog  (日)    [継承]
7.(英) KeywordList.Keyword: safety PET tracer  (日)    [継承]

標準的な表示

和文冊子 ● Tsuyoshi Tahara, Shuhei Takatani, Mieko Tsuji, Nina Shibata, Nami Hosaka, Michiko Inoue, Masahiro Ohno, Daiki Ozaki, Aya Mawatari, Yasuyoshi Watanabe, Hisashi Doi and Hirotaka Onoe : Characteristic Evaluation of a 11C-Labeled Leucine Analog, l-α-[5-11C]methylleucine, as a Tracer for Brain Tumor Imaging by Positron Emission Tomography, Molecular Pharmaceutics, Vol.20, No.3, 1842-1849, 2023.
欧文冊子 ● Tsuyoshi Tahara, Shuhei Takatani, Mieko Tsuji, Nina Shibata, Nami Hosaka, Michiko Inoue, Masahiro Ohno, Daiki Ozaki, Aya Mawatari, Yasuyoshi Watanabe, Hisashi Doi and Hirotaka Onoe : Characteristic Evaluation of a 11C-Labeled Leucine Analog, l-α-[5-11C]methylleucine, as a Tracer for Brain Tumor Imaging by Positron Emission Tomography, Molecular Pharmaceutics, Vol.20, No.3, 1842-1849, 2023.

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