ID 112381
著者
Li, Huizi Keiko National Institutes for Quantum and Radiological Science and Technology|Chiba University|Japan Society for the Promotion of Science
Sugyo, Aya National Institutes for Quantum and Radiological Science and Technology
Tsuji, Atsushi B. National Institutes for Quantum and Radiological Science and Technology
Morokoshi, Yukie National Institutes for Quantum and Radiological Science and Technology
Minegishi, Katsuyuki National Institutes for Quantum and Radiological Science and Technology
Nagatsu, Kotaro National Institutes for Quantum and Radiological Science and Technology
Kanda, Hiroaki Japanese Foundation for Cancer Research
Harada, Yosuke OncoTherapy Science Inc.
Nagayama, Satoshi Japanese Foundation for Cancer Research
Nakamura, Yusuke The University of Chicago
Higashi, Tatsuya National Institutes for Quantum and Radiological Science and Technology
Hasegawa, Sumitaka National Institutes for Quantum and Radiological Science and Technology
キーワード
α-particle
β-particle
frizzled homolog 10
radioimmunotherapy
synovial sarcoma
資料タイプ
学術雑誌論文
抄録
Synovial sarcoma (SS) is a rare yet refractory soft‐tissue sarcoma that predominantly affects young adults. We show in a mouse model that radioimmunotherapy (RIT) with an α‐particle emitting anti‐Frizzled homolog 10 (FZD10) antibody, synthesized using the α‐emitter radionuclide astatine‐211 (211At‐OTSA101), suppresses the growth of SS xenografts more efficiently than the corresponding β‐particle emitting anti‐FZD10 antibody conjugated with the β‐emitter yettrium‐90 (90Y‐OTSA101). In biodistribution analysis, 211At was increased in the SS xenografts but decreased in other tissues up to 1 day after injection as time proceeded, albeit with a relatively higher uptake in the stomach. Single 211At‐OTSA101 doses of 25 and 50 μCi significantly suppressed SS tumor growth in vivo, whereas a 50‐μCi dose of 90Y‐OTSA101 was needed to achieve this. Importantly, 50 μCi of 211At‐OTSA101 suppressed tumor growth immediately after injection, whereas this effect required several days in the case of 90Y‐OTSA101. Both radiolabeled antibodies at the 50‐μCi dosage level significantly prolonged survival. Histopathologically, severe cellular damage accompanied by massive cell death was evident in the SS xenografts at even 1 day after the 211At‐OTSA101 injection, but these effects were relatively milder with 90Y‐OTSA101 at the same timepoint, even though the absorbed doses were comparable (3.3 and 3.0 Gy, respectively). We conclude that α‐particle RIT with 211At‐OTSA101 is a potential new therapeutic option for SS.
掲載誌名
Cancer Science
ISSN
13497006
出版者
Japanese Cancer Association
109
7
開始ページ
2302
終了ページ
2309
発行日
2018-06-27
権利情報
© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
先端酵素学研究所