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Inhibition of organic cation transporter reduces non-specific uptake of MABG
https://repo.qst.go.jp/records/72766
https://repo.qst.go.jp/records/72766663b6e47-256c-4fb3-a8af-85eaa9860b19
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2018-05-01 | |||||
| タイトル | ||||||
| タイトル | Inhibition of organic cation transporter reduces non-specific uptake of MABG | |||||
| 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_c94f | |||||
| 資源タイプ | conference object | |||||
| 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 |
大島, 康宏
× 大島, 康宏× 渡辺, 茂樹× 坂下, 哲哉× 佐々木, 一郎× 東, 達也× 石岡, 典子× 大島 康宏× 渡辺 茂樹× 坂下 哲哉× 佐々木 一郎× 東 達也× 石岡 典子 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Background / Aims: We have developed meta-[211At]astato-benzylguanidine (MABG) for targeted alpha-radionuclide therapy of malignant pheochromocytoma and shown its high antitumor effects in tumor-bearing mice. However, body weight loss, an indicator of toxicity, was transiently observed at therapeutic dose. In this study, we investigated for alleviation of toxicity whether non-specific uptake of MABG could be reduced by inhibiting organic cation transporter (OCT). Methods: The uptake of MABG was examined using the following cell lines, PC-12, rat pheochromocytoma, HT-29, human colorectal adenocarcinoma, ACHN, human renal cell adenocarcinoma, BxPC-3, human pancreatic adenocarcinoma. To inhibit OCT, cells were treated with phenoxybenzamine (POB), an inhibitor of OCT1-3, ranitidine (RAN), an inhibitor of OCT1, or hydrocortisone (HDC), an inhibitor of OCT3. Results: POB (3 μM), RAN (100 μM) and HDC (10 μM) significantly reduced the uptake of MABG in HT-29, ACHN and BxPC-3. While, the uptake of MABG in PC-12 was slightly inhibited by treatment with POB, but not RAN and HDC. These results indicate that OCT1 and OCT3 were involved in the uptake of MABG in HT-29, ACHN and BxPC-3, but not in PC-12. Therefore, RAN or HDC possibly inhibit the non-specific uptake of MABG in colon, kidney and pancreas. Dose-response study showed that the inhibitory effect of RAN and HDC in HT-29, ACHN and BxPC-3 was enhanced dose-dependently. However, high-dose of RAN (1000 μM), but not HDC (100 μM), reduced the uptake of MABG in PC-12. These results suggest that HDC can inhibit the nonspecific uptake of MABG more selectively. Conclusion: Our results showed that the non-specific uptake of MABG is possibly reduced by inhibiting OCT1 and OCT3. Furthermore, HDC is a clinically approved drug, and can be a selective inhibitor for reducing non-specific uptake of MABG. At present, we are investigating the usefulness of HDC in tumor-bearing mice. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 12th World Congress of The World Federation of Nuclear Medicine and Biology (WFNMB2018) | |||||
| 発表年月日 | ||||||
| 日付 | 2018-04-23 | |||||
| 日付タイプ | Issued | |||||
