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123I-iomazenil whole-body imaging to detect hepatic carboxylesterase drug-metabolizing enzyme activity
https://repo.qst.go.jp/records/81169
https://repo.qst.go.jp/records/8116963b185fb-6c99-4a55-bf9a-1d1f8e6f94c6
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
123I-iomazenil whole-body imaging to detect hepatic carboxylesterase drug-metabolizing enzyme activity.pdf (1.7 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2020-12-02 | |||||
| タイトル | ||||||
| タイトル | 123I-iomazenil whole-body imaging to detect hepatic carboxylesterase drug-metabolizing enzyme activity | |||||
| 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 |
A, Mizutani,
× A, Mizutani,× M, Kobayashi,× KI, Fujita,× K, Takahashi,× T, Hokama,× H., Takasu,× K, Nishi,× Nishii, Ryuichi× N, Shikano,× K, Fukuchi,× K, Kawai,× Ryuichi, Nishii |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | OBJECTIVES: Drugs are mainly metabolized by hepatic enzymes, the activity of which can differ between individuals. Although it is ideal to measure the hepatic clearance of liver-targeted drugs in individualized medicine, blood enzyme tests typically measure metabolic drug clearance in the entire body, and not just in the liver. We investigated whether I-iomazenil imaging can directly assess and quantify the activity of hepatic drug-metabolizing enzymes. MATERIALS AND METHODS: Hepatic enzymes that metabolize I-iomazenil were identified by thin-layer chromatography in mouse liver homogenates with bis(4-nitrophenyl) phosphate (BNPP) inhibitor for carboxylesterase enzymes and nicotinamide adenine dinucleotide phosphate (NADPH) generator for cytochrome P450 enzymes. Whole-body images of mice were acquired using I-iomazenil with and without BNPP, and the distribution was also obtained. The metabolism of I-iomazenil in the blood, liver, gall bladder, and bladder was investigated by thin-layer chromatography. RESULTS: From the in-vitro metabolism of I-iomazenil using BNPP, the enzyme converting I-iomazenil to I-R-COOH was identified as carboxylesterase, and that converting I-iomazenil to M2 was identified as cytochrome P450 in experiments with and without an NADPH generator. The biological distribution and whole-body imaging showed increased accumulation in the liver of mice administered BNPP compared with normal mice, but decreased levels in the gall bladder and small intestine. The main fraction in bile and urine was I-R-COOH, with two unknown metabolites (M1 and M2), I, and I-iomazenil also being present. CONCLUSION: I-iomazenil whole-body imaging has good possibility of direct measurement of hepatic carboxylesterase activity as accumulation of I-R-COOH in the gall bladder through bile and in the bladder through urine. | |||||
| 書誌情報 |
Nuclear Medicine Communications 巻 39, 号 9, p. 825-833, 発行日 2018-09 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0143-3636 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 29877992 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1097/MNM.0000000000000875 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://journals.lww.com/nuclearmedicinecomm/Abstract/2018/09000/123I_iomazenil_whole_body_imaging_to_detect.4.aspx | |||||
