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Assessment of drug transporters involved in the urinary secretion of [99mTc]dimercaptosuccinic acid
https://repo.qst.go.jp/records/81843
https://repo.qst.go.jp/records/818433c087dd4-2cc5-44b1-b181-3c7ce3d22f3a
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-02-16 | |||||
| タイトル | ||||||
| タイトル | Assessment of drug transporters involved in the urinary secretion of [99mTc]dimercaptosuccinic acid | |||||
| 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 |
M, Kobayashi
× M, Kobayashi× A, Mizutani× T, Okamoto× Y, Muranaka× K, Nishi× Ryuichi, Nishii× N, Shikano× T, Nakanishi× I, Tamai× ES, Kleinerman× K, Kawai× Ryuichi, Nishii |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | ABSTRACT Introduction: We clarified the renal uptake and urinary secretion mechanism of [99mTc]dimercaptosuccinic acid ([99mTc]DMSA) via drug transporters in renal proximal tubules. Methods: [99mTc]DMSA was added to human embryonic kidney 293 cells expressing human multidrug and toxin extrusion (MATE)1 and MATE2-K, carnitine/organic cation transporter (OCTN)1 and OCTN2, and organic cation transporter (OCT)2; to Flp293 cells expressing human organic anion transporter (OAT)1 and OAT3; and to vesicles expressing P-glycoprotein (P-gp), multidrug resistance associated protein (MRP)2, MRP4, or breast cancer resistance protein with and without probenecid (OAT inhibitor for both OATs and MRPs). Time activity curves of [99mTc]DMSA with and without probenecid were established using LLC-PK1 cells. Biodistribution and single photon emission computed tomography (SPECT) imaging in mice were conducted using [99mTc]DMSA with and without probenecid. Results: [99mTc]DMSA uptake was significantly higher in Flp293/OAT3 than in mock cells. Uptake via OAT3 was inhibited by probenecid. [99mTc]DMSA uptake into vesicles that highly expressed MRP2 was significantly higher in adenosine triphosphate (ATP) than in adenosine monophosphate (AMP), and probenecid decreased uptake to similar levels as that in AMP. In the time activity curves for [99mTc]DMSA in LLC-PK1 cells, probenecid loading inhibited accumulation from the basolateral side into LLC-PK1 cells, whereas accumulation from the apical side into cells gradually increased. Transport of [99mTc]DMSA from both sides was low. Biodistribution and SPECT imaging studies showed that [99mTc]DMSA with probenecid loading resulted in significantly higher accumulation in blood, heart, liver, and bladder after [99mTc]DMSA injection compared with control mice. Probenecid induced significantly lower accumulation in the kidney after [99mTc]DMSA injection. Conclusions: [99mTc]DMSA accumulates in renal proximal tubular epithelial cells from blood via OAT3 on the basolateral side, and then a small volume of [99mTc]DMSA will be excreted in urine via MRP2. Advances in knowledge: [99mTc]DMSA accumulates via OAT3 in renal proximal tubular epithelial cells and is slightly excreted from the cells via MRP2. Implications for patient care: [99mTc]DMSA may be useful for measuring renal transport function with OAT3 in patients. |
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| 書誌情報 |
Nuclear Medicine and Biology 巻 94-95, p. 92-97, 発行日 2021-02 |
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| 出版者 | ||||||
| 出版者 | Elsevier | |||||
| 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.2021.01.004 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.sciencedirect.com/science/article/pii/S0969805121000251 | |||||
