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α-particle therapy for synovial sarcoma in the mouse using an astatine-211-labeled antibody against frizzled homolog 10α-particle therapy for synovial sarcoma in the mouse using an astatine-211-labeled antibody against frizzled homolog 10 |
"/Li, Huizi/"Li, Huizi ,
"/Sugyo, Aya/"Sugyo, Aya ,
"/Tsuji, Atsushi/"Tsuji, Atsushi ,
"/Morokoshi, Yukie/"Morokoshi, Yukie ,
"/Minegishi, Katsuyuki/"Minegishi, Katsuyuki ,
"/Nagatsu, Kotaro/"Nagatsu, Kotaro ,
"/Kanda, Hiroaki/"Kanda, Hiroaki ,
"/Harada, Yosuke/"Harada, Yosuke ,
"/Nagayama, Satoshi/"Nagayama, Satoshi ,
"/Katagiri, Toyomasa/"Katagiri, Toyomasa ,
"/Nakamura, Yusuke/"Nakamura, Yusuke ,
"/Higashi, Tatsuya/"Higashi, Tatsuya ,
"/Hasegawa, Sumitaka/"Hasegawa, Sumitaka
109
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7
)
, pp.2302
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2309 , 2018-07
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 (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.