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 -particle emitting anti-Frizzled homolog 10 (FZD10) antibody, synthesized using the -emitter radionuclide astatine-211 (At-211-OTSA101), suppresses the growth of SS xenografts more efficiently than the corresponding -particle emitting anti-FZD10 antibody conjugated with the -emitter yettrium-90 (Y-90-OTSA101). In biodistribution analysis, At-211 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 At-211-OTSA101 doses of 25 and 50 Ci significantly suppressed SS tumor growth in vivo, whereas a 50-Ci dose of Y-90-OTSA101 was needed to achieve this. Importantly, 50 Ci of At-211-OTSA101 suppressed tumor growth immediately after injection, whereas this effect required several days in the case of Y-90-OTSA101. Both radiolabeled antibodies at the 50-Ci 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 At-211-OTSA101 injection, but these effects were relatively milder with Y-90-OTSA101 at the same timepoint, even though the absorbed doses were comparable (3.3 and 3.0 Gy, respectively). We conclude that -particle RIT with At-211-OTSA101 is a potential new therapeutic option for SS.