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Favorable tumor uptake and nuclear transport of Auger electrons by nuclear targeting with 111In-trastuzumab in an intraperitoneal tumor mouse model
https://repo.qst.go.jp/records/86070
https://repo.qst.go.jp/records/86070d314e470-79f6-47c9-b991-0a9b0cd75efb
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2022-05-05 | |||||
| タイトル | ||||||
| タイトル | Favorable tumor uptake and nuclear transport of Auger electrons by nuclear targeting with 111In-trastuzumab in an intraperitoneal tumor mouse model | |||||
| 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 |
Li, Huizi
× Li, Huizi× Sumitaka, Hasegawa× Li, Huizi× Sumitaka, Hasegawa |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives: The 111In-labeled anti-HER2 antibody trastuzumab modified with a nuclear-localizing sequence (NLS) peptide (111In-trastuzumab-NLS) is a radiopharmaceutical candidate for Auger electron radioimmunotherapy (AE-RIT). However, in vivo action of 111In-trastuzumab-NLS is poorly understood in intraperitoneal tumors. We aimed to elucidate the nuclear targeting activity of 111In-trastuzumab-NLS in a mouse model of intraperitoneal tumors. Methods: Trastuzumab, trastuzumab-NLS-S with shorter NLS peptides, and trastuzumab-NLS-L with longer NLS peptides were tested in an intraperitoneal tumor xenograft. The AE-emitting radionuclide 111In was labeled with these antibodies. The cell binding activity, nuclear importation, and cytotoxicity of those radiolabeled antibodies were examined in human cancer cell lines. Analyses of the biodistribution and in vivo nuclear importation of 111In were conducted in a mouse model. Results: The two111In-trastuzumab-NLS variants delivered the radionuclide into the nucleus more efficiently and had a comparable cytotoxicity to 111In-trastuzumab against human gastric cancer cells, although had a lower cell binding affinity. 111In-trastuzumab-NLS-L exhibited both a superior tumor uptake and in vivo nuclear transportation of the radionuclide than 111In-trastuzumab. Conclusions: Nuclear targeting using 111In-trastuzumab-NLS promotes a more efficient tumor cell uptake and subsequent nuclear translocation of the 111In AE-emitting radionuclide in vivo. This radio-immunoconjugate will likely be an effective agent for HER2-targeting by AE-RIT. |
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| 書誌情報 |
Nuclear Medicine Communications 巻 43, 号 7, p. 763-769, 発行日 2022-05 |
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| 出版者 | ||||||
| 出版者 | Lippincott Williams & Wilkins | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0143-3636 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1097/MNM.0000000000001571 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://journals.lww.com/nuclearmedicinecomm/Abstract/2022/07000/Favorable_tumor_uptake_and_nuclear_transport_of.4.aspx# | |||||
