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Organic cation transporter 3 mediates the non-norepinephrine transporter driven uptake of meta-[211At]astato-benzylguanidine
https://repo.qst.go.jp/records/2000166
https://repo.qst.go.jp/records/200016608957afa-ff2d-4d3b-8d1c-a812b4ca2288
| アイテムタイプ | 学術雑誌論文 / Journal Article(1) | |||||||||||||||||
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| 公開日 | 2023-06-28 | |||||||||||||||||
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| タイトル | Organic cation transporter 3 mediates the non-norepinephrine transporter driven uptake of meta-[211At]astato-benzylguanidine | |||||||||||||||||
| 言語 | en | |||||||||||||||||
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| 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 |
Oshima Yasuhiro
× Oshima Yasuhiro
× Sasaki Ichiro
× Watanabe Shigeki
× Sakashita Tetsuya
× Higashi Tatsuya
× Ishioka Noriko
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| 抄録 | ||||||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||||||
| 内容記述 | Introduction: Meta-[211At]astato-benzylguanidine ([211At]MABG) accumulates in pheochromocytoma via norepinephrine transporter (NET) and leads to a strong antitumor effect, but it also distributed in normal tissues non-specifically. Meta-[131I]iodo-benzylguanidine ([131I]MIBG), an iodine-labeled analog of [211At]MABG, is known to be transported by not only NET but also organic cation transporter (OCT). The involvement of OCT in [211At]MABG uptake is still largely unknown. We investigated the involvement of OCT in the non-NET-driven uptake of [211At]MABG both in vitro and in vivo. Methods: [123I]MIBG and [211At]MABG uptake was investigated in PC-12 (rat pheochromocytoma cell line), NIH/3T3 (mouse fibroblasts cell line), ACHN (human renal cancer cell line), and BxPC-3 (human pancreatic cancer cell line). Herein, we used desipramine and dl-norepinephrine to inhibit NET, and we used steroids (hydrocortisone and prednisolone) to inhibit OCT3. The [211At]MABG uptake in OCT3-knockdown cells established with OCT3-selective siRNA was also investigated. We investigated the biodistribution of [211At]MABG in PC-12 tumor-bearing mice after a preloading of phosphate-buffered saline (PBS) or hydrocortisone solution. Results: The uptake of both [123I]MIBG and [211At]MABG was significantly inhibited by desipramine in PC-12 cells but not the other cell lines. The expression of OCT3 was relatively higher than those of the other OCT subtypes in ACHN and BxPC-3 cells. The expression of OCTs was not observed in NIH/3T3 cells. The uptake of both [123I]MIBG and [211At]MABG in ACHN and BxPC-3 cells was significantly inhibited by the steroid treatments. The [211At]MABG uptake was also reduced in OCT3-knockdown cells (p<0.001). The radioactivity of [211At]MABG was significantly reduced in normal tissues by the preloading of hydrocortisone. In contrast, there was an increasing trend of [211At]MABG uptake in the PC-12 tumors. The tumor-to-normal tissue ratio was significantly increased by the preloading of hydrocortisone compared to that of PBS. Conclusion: Our results suggest that OCT3 is involved in non-NET-driven [211At]MABG uptake. The preloading of hydrocortisone selectively reduced [211At]MABG accumulation in normal organs in vivo. OCT3 inhibition may therefore be beneficial for a reduction of the radiation risk in healthy organs in the treatment of malignant pheochromocytomas. |
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| 書誌情報 |
Nuclear medicine and biology 巻 112-113, p. 44-51, 発行日 2022-06 |
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| 出版者 | Elsevier | |||||||||||||||||
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| 収録物識別子タイプ | ISSN | |||||||||||||||||
| 収録物識別子 | 0969-8051 | |||||||||||||||||
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| 識別子タイプ | PMID | |||||||||||||||||
| 関連識別子 | 35802985 | |||||||||||||||||
| DOI | ||||||||||||||||||
| 識別子タイプ | DOI | |||||||||||||||||
| 関連識別子 | 10.1016/j.nucmedbio.2022.06.005 | |||||||||||||||||
