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  1. C. 医薬保健学域; 医学類・薬学類・医薬科学類・保健学類
  2. c 10. 学術雑誌掲載論文(医・保健)
  3. 1. 査読済論文(医学・保健)

An artificial amino acid, 4-iodo-L-meta-tyrosine: Biodistribution and excretion via kidney

http://hdl.handle.net/2297/2789
http://hdl.handle.net/2297/2789
3499554e-1cbf-412c-8272-14d18a5e233f
名前 / ファイル ライセンス アクション
ME-PR-SHIKANO-N-625.pdf ME-PR-SHIKANO-N-625.pdf (302.4 kB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2017-10-03
タイトル
タイトル An artificial amino acid, 4-iodo-L-meta-tyrosine: Biodistribution and excretion via kidney
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
著者 Shikano, Naoto

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Shikano, Naoto

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Kawai, Keiichi

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e-Rad 30204663
金沢大学研究者情報 30204663
研究者番号 30204663

Kawai, Keiichi

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Garcia Flores II, Leo

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Garcia Flores II, Leo

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Nishii, Ryuichi

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Nishii, Ryuichi

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Kubota, Nobuo

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Kubota, Nobuo

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Ishikawa, Nobuyoshi

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Ishikawa, Nobuyoshi

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Kubodera, Akiko

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Kubodera, Akiko

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提供者所属
内容記述タイプ Other
内容記述 金沢大学大学院医学系研究科
書誌情報 Journal of Nuclear Medicine

巻 44, 号 4, p. 625-631, 発行日 2003-04-01
ISSN
収録物識別子タイプ ISSN
収録物識別子 0161-5505
NCID
収録物識別子タイプ NCID
収録物識別子 AA00703684
出版者
出版者 THE SOCIETY OF NUCLEAR MEDICINE INC
抄録
内容記述タイプ Abstract
内容記述 We evaluated the use of radiolabeled 4-iodo-L-meta-tyrosine as an amino acid transport marker. The pharmacologic features of this compound, particularly the biodistribution and excretion, were examined by conducting in vivo and in vitro studies using 4-125I-iodo-L-meta-tyrosine (4- 125I-mTyr). Results obtained for L-14C-Tyr and 3- 125I-iodo-α-methyl-L-tyrosine (125I-IMT) were used for comparison. Methods: In vivo biodistribution studies of 4- 125I-mTyr were performed in male ddY mice. Urinary excretion of 4-125I-mTyr and 125I-IMT with administration of probenecid was studied. Local distribution of 4-125I-mTyr and 125I-IMT in kidney was visualized by autoradiography. We performed metabolite analysis of 4-125I-mTyr in mice. For in vitro studies, reabsorption mechanisms of 4-125I-mTyr were compared with those of 125I-IMT and the parent L-14C-Tyr using superconfluent monolayers of the porcine kidney epithelial cell line LLC-PK1 in medium containing inhibitor (L-Tyr, D-Tyr, and 2,4-dinitrophenol), in Na +-free medium, and at 4°C. Results: 4-125I-mTyr demonstrated high accumulation in the pancreas and kidney and comparable brain uptake to that of 125I-IMT. Blood clearance of 4-125I-mTyr was faster than that of 125I-IMT. Three hours after administration, >70% of 4-125I-mTyr was excreted via the urine, whereas <5% was found in the feces. Renal autoradiography revealed moderate accumulation of 4-125I-mTyr and high accumulation of 125I-IMT in the renal cortex. Probenecid further reduced accumulation of 4-125I-mTyr and 125I-IMT in the kidney as well as urinary excretion. At 30 min after tracer injection, intact free 4-125I-mTyr accounted for >98.1% of the total present in kidney and >96.3% in urine. Protein incorporation was not observed. Uptake of 4-125I-mTyr into LLC-PK1 cell monolayers was remarkably reduced by 5 mmol/L L-Tyr (4.6%) and incubation at 4°C (15.6%) but was reduced by 5 mmol/L D-Tyr (50.0%). L-14C-Tyr and 125I-IMT showed similar results; however, uptake of 125I-IMT was enhanced by 0.1 mmol/L 2,4-dinitrophenol (165.1%), an inhibitor of generation of energy-rich phosphates. Conclusion: The artificial amino acid 4-125I-mTyr demonstrated high metabolic stability, rapid blood clearance, rapid urinary excretion, and similar biodistribution to other radioiabeled L-Tyr analogs. 4-125I-mTyr can be a competitive substrate of L-Tyr reabsorption. However, 4-125I-mTyr demonstrates different pharmacologic features than those of 125I-IMT, particularly in renal handling. 4-125I-mTyr may potentially be applied as a new amino acid transport marker.
著者版フラグ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
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