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α‐particle therapy for synovial sarcoma in the mouse using an astatine‐211‐labeled antibody against frizzled homolog 10

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 ((211)At...

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Autores principales: Li, Huizi Keiko, Sugyo, Aya, Tsuji, Atsushi B., Morokoshi, Yukie, Minegishi, Katsuyuki, Nagatsu, Kotaro, Kanda, Hiroaki, Harada, Yosuke, Nagayama, Satoshi, Katagiri, Toyomasa, Nakamura, Yusuke, Higashi, Tatsuya, Hasegawa, Sumitaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029834/
https://www.ncbi.nlm.nih.gov/pubmed/29952132
http://dx.doi.org/10.1111/cas.13636
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author Li, Huizi Keiko
Sugyo, Aya
Tsuji, Atsushi B.
Morokoshi, Yukie
Minegishi, Katsuyuki
Nagatsu, Kotaro
Kanda, Hiroaki
Harada, Yosuke
Nagayama, Satoshi
Katagiri, Toyomasa
Nakamura, Yusuke
Higashi, Tatsuya
Hasegawa, Sumitaka
author_facet Li, Huizi Keiko
Sugyo, Aya
Tsuji, Atsushi B.
Morokoshi, Yukie
Minegishi, Katsuyuki
Nagatsu, Kotaro
Kanda, Hiroaki
Harada, Yosuke
Nagayama, Satoshi
Katagiri, Toyomasa
Nakamura, Yusuke
Higashi, Tatsuya
Hasegawa, Sumitaka
author_sort Li, Huizi Keiko
collection PubMed
description 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 ((211)At‐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 ((90)Y‐OTSA101). In biodistribution analysis, (211)At 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 (211)At‐OTSA101 doses of 25 and 50 μCi significantly suppressed SS tumor growth in vivo, whereas a 50‐μCi dose of (90)Y‐OTSA101 was needed to achieve this. Importantly, 50 μCi of (211)At‐OTSA101 suppressed tumor growth immediately after injection, whereas this effect required several days in the case of (90)Y‐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 (211)At‐OTSA101 injection, but these effects were relatively milder with (90)Y‐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 (211)At‐OTSA101 is a potential new therapeutic option for SS.
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spelling pubmed-60298342018-07-09 α‐particle therapy for synovial sarcoma in the mouse using an astatine‐211‐labeled antibody against frizzled homolog 10 Li, Huizi Keiko Sugyo, Aya Tsuji, Atsushi B. Morokoshi, Yukie Minegishi, Katsuyuki Nagatsu, Kotaro Kanda, Hiroaki Harada, Yosuke Nagayama, Satoshi Katagiri, Toyomasa Nakamura, Yusuke Higashi, Tatsuya Hasegawa, Sumitaka Cancer Sci Original Articles 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 ((211)At‐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 ((90)Y‐OTSA101). In biodistribution analysis, (211)At 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 (211)At‐OTSA101 doses of 25 and 50 μCi significantly suppressed SS tumor growth in vivo, whereas a 50‐μCi dose of (90)Y‐OTSA101 was needed to achieve this. Importantly, 50 μCi of (211)At‐OTSA101 suppressed tumor growth immediately after injection, whereas this effect required several days in the case of (90)Y‐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 (211)At‐OTSA101 injection, but these effects were relatively milder with (90)Y‐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 (211)At‐OTSA101 is a potential new therapeutic option for SS. John Wiley and Sons Inc. 2018-06-27 2018-07 /pmc/articles/PMC6029834/ /pubmed/29952132 http://dx.doi.org/10.1111/cas.13636 Text en © 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 http://creativecommons.org/licenses/by-nc-nd/4.0/ 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.
spellingShingle Original Articles
Li, Huizi Keiko
Sugyo, Aya
Tsuji, Atsushi B.
Morokoshi, Yukie
Minegishi, Katsuyuki
Nagatsu, Kotaro
Kanda, Hiroaki
Harada, Yosuke
Nagayama, Satoshi
Katagiri, Toyomasa
Nakamura, Yusuke
Higashi, Tatsuya
Hasegawa, Sumitaka
α‐particle therapy for synovial sarcoma in the mouse using an astatine‐211‐labeled antibody against frizzled homolog 10
title α‐particle therapy for synovial sarcoma in the mouse using an astatine‐211‐labeled antibody against frizzled homolog 10
title_full α‐particle therapy for synovial sarcoma in the mouse using an astatine‐211‐labeled antibody against frizzled homolog 10
title_fullStr α‐particle therapy for synovial sarcoma in the mouse using an astatine‐211‐labeled antibody against frizzled homolog 10
title_full_unstemmed α‐particle therapy for synovial sarcoma in the mouse using an astatine‐211‐labeled antibody against frizzled homolog 10
title_short α‐particle therapy for synovial sarcoma in the mouse using an astatine‐211‐labeled antibody against frizzled homolog 10
title_sort α‐particle therapy for synovial sarcoma in the mouse using an astatine‐211‐labeled antibody against frizzled homolog 10
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029834/
https://www.ncbi.nlm.nih.gov/pubmed/29952132
http://dx.doi.org/10.1111/cas.13636
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