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

Abstract

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.