Abstract

This first-in-human study examined the safety and therapeutic potential of [²¹¹At]NaAt, a novel alpha-particle therapy using astatine-211, in eleven patients with radioiodine-refractory differentiated thyroid cancer (DTC). The study employed a modified 3+3 dose-escalation design with doses of 1.25, 2.5, and 3.5 MBq/kg. Dose-limiting toxicities (DLTs) consisting of grade 3 leukopenia and lymphopenia were observed in 50% of patients at the 3.5 MBq/kg dose. Non-hematologic adverse events included transient salivary gland swelling, nausea, and gastrointestinal effects, predominantly at doses ≥2.5 MBq/kg. Remarkably, hematologic toxicities were transient with complete recovery by 8 weeks. Therapeutic efficacy assessment showed ≥50% thyroglobulin reduction in 33% of patients at both 2.5 and 3.5 MBq/kg doses. At 6 months, 90% of patients achieved stable disease, with partial or complete responses observed on [¹³¹I]SPECT imaging. The recommended Phase 2 dose was determined to be 2.5 MBq/kg based on the favorable tolerability profile and preliminary evidence of therapeutic benefit. This study provides the first clinical evidence that [²¹¹At]NaAt is a safe and effective treatment option for RAI-refractory thyroid cancer.

Publication Information

Journal: Journal of Nuclear Medicine

Publication Type: Early Online Publication

Publication Date: September 25, 2025

DOI: 10.2967/jnumed.125.270810

Journal Link: https://jnm.snmjournals.org/content/early/2025/09/25/jnumed.125.270810

Authors

Tadashi Watabe, Kosuke Mukai, Sadahiro Naka, Hisashi Sasaki, Takahiro Kamiya, Tomohiro Hayakawa, Akira Fukuhara, Takeshi Takano, Yuri Shirakami, Kenji Ooe, Sachiko Shigeno, Shota Okamura, Keisuke Masumura, Eiichi Hida, Hideki Haba, Akira Toyoshima, Kenji Isohashi, Iichiro Shimomura, Naoki Tomiyama

Institutional Affiliations: University of Osaka Hospital, RIKEN Nishina Center for Accelerator-Based Science, Research Center for Nuclear Physics (RCNP), University of Osaka, Japan

Trial Registration: NCT05275946 (Alpha-T1 Trial, 11 patients, February 2022 – May 2024)

Funding: AMED Clinical Research and Trial Promotion Research Project (grant 23lk0201139h0003) and Alpha-Fusion, Inc.