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‐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.