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Ref Type Journal Article
PMID (29952132)
Authors Li HK, Sugyo A, Tsuji AB, Morokoshi Y, Minegishi K, Nagatsu K, Kanda H, Harada Y, Nagayama S, Katagiri T, Nakamura Y, Higashi T, Hasegawa S
Title α-particle therapy for synovial sarcoma in the mouse using an astatine-211-labeled antibody against frizzled homolog 10.
Journal Vol Issue Date Pages Journal Short Title
Cancer science 109 7 2018 Jul 2302-2309 Cancer Sci
URL
Abstract Text 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
211At-OTSA101 211At-OTSA101 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
211At-OTSA101 211At-OTSA101 is an FZD10 antibody radiolabeled with astatine (At)-211, which may lead to a cytotoxic effect and tumor growth inhibition (PMID: 29952132).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References