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Synovial sarcomas are rare tumors arising in adolescents and young adults. The prognosis for advanced disease is poor, with an overall survival of 12‐18 months. Frizzled homolog 10 (FZD10) is overexpressed in most synovial sarcomas, making it a promising therapeutic target. The results of a phase 1 trial of β‐radioimmunotherapy (RIT) with the 90Y‐labeled anti‐FZD10 antibody OTSA101 revealed a need for improved efficacy. The present study evaluated the potential of α‐RIT with OTSA101 labeled with the α‐emitter 225Ac. Competitive inhibition and cell binding assays showed that specific binding of 225Ac‐labeled OTSA101 to SYO‐1 synovial sarcoma cells was comparable to that of the imaging agent 111In‐labeled OTSA101. Biodistribution studies showed high uptake in SYO‐1 tumors and low uptake in normal organs, except for blood. Dosimetric studies showed that the biologically effective dose (BED) of 225Ac‐labeled OTSA101 for tumors was 7.8 Bd higher than that of 90Y‐labeled OTSA101. 90Y‐ and 225Ac‐labeled OTSA101 decreased tumor volume and prolonged survival. 225Ac‐labeled OTSA101 achieved a complete response in 60% of mice, and no recurrence was observed. 225Ac‐labeled OTSA101 induced a larger amount of necrosis and apoptosis than 90Y‐labeled OTSA101, although the cell proliferation decrease was comparable. The BED for normal organs and tissues was tolerable; no treatment‐related mortality or obvious toxicity, except for temporary body weight loss, was observed. 225Ac‐labeled OTSA101 provided a high BED for tumors and achieved a 60% complete response in the synovial sarcoma mouse model SYO‐1. RIT with 225Ac‐labeled OTSA101 is a promising therapeutic option for synovial sarcoma. FZD10‐targeted alpha‐radioimmunotherapy with 225Ac‐labeled OTSA101 provided a high radiation dose to tumors and achieved 60% complete response in the synovial sarcoma mouse model SYO‐1. This is the best outcome among FZD10‐targeted therapy to date. Our alpha‐radioimmunotherapy would provide an additional therapeutic option to synovial sarcoma patients that do not show a good response to conventional therapy.

The fundamental physical quantity for relating all biologic effects to radiation exposure is the absorbed dose, the energy imparted per unit mass of tissue. Absorbed dose is expressed in units of joules per kilogram (J/kg) and is given the special name gray (Gy). Exposure to ionizing radiation may cause both deterministic and stochastic biologic effects. To account for the relative effect per unit absorbed dose that has been observed for different types of radiation, the International Commission on Radiological Protection (ICRP) has established radiation weighting factors for stochastic effects. The product of absorbed dose in Gy and the radiation weighting factor is defined as the equivalent dose. Equivalent dose values are designated by a special named unit, the sievert (Sv). Unlike the situation for stochastic effects, no well-defined formalism and associated special named quantities have been widely adopted for deterministic effects. The therapeutic application of radionuclides and, specifically, alpha-particle emitters in nuclear medicine has brought to the forefront the need for a well-defined dosimetry formalism applicable to deterministic effects that is accompanied by corresponding special named quantities. This commentary reviews recent proposals related to this issue and concludes with a recommendation to establish a new named quantity.