ID | 117212 |
著者 |
Sudo, Hitomi
National Institutes for Quantum and Radiological Science and Technology
Tsuji, Atsushi B.
National Institutes for Quantum and Radiological Science and Technology
Sugyo, Aya
National Institutes for Quantum and Radiological Science and Technology
Harada, Yosuke
OncoTherapy Science Inc.
Nagayama, Satoshi
Uji Tokushukai Medical Center
Nakamura, Yusuke
Japanese Foundation for Cancer Research
Higashi, Tatsuya
National Institutes for Quantum and Radiological Science and Technology
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キーワード | barendsen unit
complete response
molecular radiotherapy
relative biological effect
therapeutic nuclear medicine
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資料タイプ |
学術雑誌論文
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抄録 | Synovial sarcomas are rare tumors arising in adolescents and young adults. The prognosis for advanced disease is poor, with an overall survival of 12-18 months. Frizzled homolog 10 (FZD10) is overexpressed in most synovial sarcomas, making it a promising therapeutic target. The results of a phase 1 trial of β-radioimmunotherapy (RIT) with the 90Y-labeled anti-FZD10 antibody OTSA101 revealed a need for improved efficacy. The present study evaluated the potential of α-RIT with OTSA101 labeled with the α-emitter 225Ac. Competitive inhibition and cell binding assays showed that specific binding of 225Ac-labeled OTSA101 to SYO-1 synovial sarcoma cells was comparable to that of the imaging agent 111In-labeled OTSA101. Biodistribution studies showed high uptake in SYO-1 tumors and low uptake in normal organs, except for blood. Dosimetric studies showed that the biologically effective dose (BED) of 225Ac-labeled OTSA101 for tumors was 7.8 Bd higher than that of 90Y-labeled OTSA101. 90Y- and 225Ac-labeled OTSA101 decreased tumor volume and prolonged survival. 225Ac-labeled OTSA101 achieved a complete response in 60% of mice, and no recurrence was observed. 225Ac-labeled OTSA101 induced a larger amount of necrosis and apoptosis than 90Y-labeled OTSA101, although the cell proliferation decrease was comparable. The BED for normal organs and tissues was tolerable; no treatment-related mortality or obvious toxicity, except for temporary body weight loss, was observed. 225Ac-labeled OTSA101 provided a high BED for tumors and achieved a 60% complete response in the synovial sarcoma mouse model SYO-1. RIT with 225Ac-labeled OTSA101 is a promising therapeutic option for synovial sarcoma.
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掲載誌名 |
Cancer Science
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ISSN | 13497006
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出版者 | Japanese Cancer Association|John Wiley & Sons
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巻 | 113
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号 | 2
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開始ページ | 721
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終了ページ | 732
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発行日 | 2021-12-21
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権利情報 | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
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著者版フラグ |
出版社版
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部局 |
先端酵素学研究所
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