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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 ( FZD 10) antibody, synthesized using the α‐emitter radionuclide astatine‐211 ( 211 At‐ OTSA 101), suppresses the growth of  SS  xenografts more efficiently than the corresponding β‐particle emitting anti‐ FZD 10 antibody conjugated with the β‐emitter yettrium‐90 ( 90 Y‐ OTSA 101). 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‐ OTSA 101 doses of 25 and 50 μCi significantly suppressed  SS  tumor growth in vivo, whereas a 50‐μCi dose of  90 Y‐ OTSA 101 was needed to achieve this. Importantly, 50 μCi of  211 At‐ OTSA 101 suppressed tumor growth immediately after injection, whereas this effect required several days in the case of  90 Y‐ OTSA 101. 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‐ OTSA 101 injection, but these effects were relatively milder with  90 Y‐ OTSA 101 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‐ OTSA 101 is a potential new therapeutic option for  SS .

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