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

Li, Huizi  ,  Sugyo, Aya  ,  Tsuji, Atsushi  ,  Morokoshi, Yukie  ,  Minegishi, Katsuyuki  ,  Nagatsu, Kotaro  ,  Kanda, Hiroaki  ,  Harada, Yosuke  ,  Nagayama, Satoshi  ,  Katagiri, Toyomasa  ,  Nakamura, Yusuke  ,  Higashi, Tatsuya  ,  Hasegawa, Sumitaka

109 ( 7 )  , pp.2302 - 2309 , 2018-07
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.

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