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Imaging of hepatic drug transporters with [131I]6-β-iodomethyl-19-norcholesterol
https://repo.qst.go.jp/records/77564
https://repo.qst.go.jp/records/7756418398c68-0df5-42f8-b128-85d3e2d8919b
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2019-11-21 | |||||
タイトル | ||||||
タイトル | Imaging of hepatic drug transporters with [131I]6-β-iodomethyl-19-norcholesterol | |||||
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 |
Kobayashi, Masato
× Kobayashi, Masato× Nishi, Kodai× Mizutani, Asuka× Tsuzumi Hokama× Matsue, Miki× TetsuyaTsujikawa× Nakanishi, Takeo× Nishii, Ryuichi× IkumiTamai× Kawai, Keiichi× Nishii, Ryuichi |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | We examined whether [131I]6-β-iodomethyl-19-norcholesterol (NP-59), a cholesterol analog, can be used to measure function of hepatic drug transporters. Hepatic uptake of NP-59 with and without rifampicin was evaluated using HEK293 cells expressing solute carrier transporters. The stability of NP-59 was evaluated using mouse blood, bile, and liver, and human liver S9. Adenosine triphosphate-binding cassette (ABC) transporters for bile excretion were examined using hepatic ABC transporter vesicles expressing multidrug resistance protein 1, multidrug resistance-associated protein (MRP)1-4, breast cancer resistance protein (BCRP), or bile salt export pump with and without MK-571 and Ko143. Single photon emission computed tomography (SPECT) was performed in normal mice injected with NP-59 in the presence or absence of Ko143. Uptake of NP-59 into HEK293 cells expressing organic anion transporting polypeptide (OATP)1B1 and OATP1B3 was significantly higher than that into mock cells and was inhibited by rifampicin. NP-59 was minimally metabolized in mouse blood, bile, and liver, and human liver S9 after 120 min of incubation. In vesicles, NP-59 was transported by MRP1 and BCRP. Excretion of NP-59 into bile via BCRP was observed in normal mice with and without Ko143 in the biological distribution and SPECT imaging. NP-59 can be used to visualize and measure the hepatic function of OATP1B1, OATP1B3, and BCRP. | |||||
書誌情報 |
Scientific Reports 巻 9, p. 13413, 発行日 2019-09 |
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出版者 | ||||||
出版者 | Springer Nature | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 2045-2322 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1038/s41598-019-50049-8 | |||||
関連サイト | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://www.nature.com/articles/s41598-019-50049-8 |