2025-10-7 大阪大学
図1.アルファ線治療薬アスタチン(²¹¹At)を用いた治療
(全身の転移巣に集積させることで、体内からアルファ線を放出)
<関連情報>
- https://resou.osaka-u.ac.jp/ja/research/2025/20251007_1
- https://jnm.snmjournals.org/content/early/2025/09/25/jnumed.125.270810
放射性ヨウ素治療抵抗性甲状腺癌患者に対する[ 211At ]NaAtを標的α線療法として用いる初のヒト臨床試験(Alpha-T1試験) First-in-Human Study of [211At]NaAt as Targeted α-Therapy in Patients with Radioiodine-Refractory Thyroid Cancer (Alpha-T1 Trial)
Tadashi Watabe, Kosuke Mukai, Sadahiro Naka, Hidetaka Sasaki, Takashi Kamiya, Tomoaki Hayakawa, Atsunori Fukuhara, Toru Takano, Yoshifumi Shirakami, Kazuhiro Ooe, Satoshi Shigeno, Satomi Okamura, Kazuho Masumura, Eisuke Hida, Hiromitsu Haba, Atsushi Toyoshima, Kayako Isohashi, Iichiro Shimomura and Noriyuki Tomiyama
Journal of Nuclear Medicine Published:September 2025
DOI:https://doi.org/10.2967/jnumed.125.270810
Abstract
211At, a cyclotron-produced α-emitter, has attracted interest as a potential alternative to radioactive iodine (RAI) because of its superior cytotoxic properties. This first-in-human prospective clinical trial aimed to evaluate the safety and preliminary efficacy of [211At]NaAt in patients with differentiated thyroid cancer (DTC). Methods: Eleven patients with metastatic RAI-refractory DTC were enrolled in this study. A single intravenous dose of [211At]NaAt was administered in the setting of recombinant human thyroid-stimulating hormone stimulation and an iodine-restricted diet. Dose escalation followed a modified 3 + 3 design, with doses of 1.25 (n = 2), 2.5 (n = 3), and 3.5 MBq/kg (n = 6). The primary endpoint was the assessment of adverse events using Common Terminology Criteria for Adverse Events version 5.0 guidelines and dose-limiting toxicities. Secondary endpoints included evaluation of pharmacokinetics, absorbed dose, and therapeutic efficacy. Results: Dose-limiting toxicities occurred in 3 of 6 patients who received 3.5 MBq/kg, consisting of grade 3 hematologic toxicity (lymphopenia or leukopenia) lasting for more than 1 wk. Other major adverse events included salivary gland swelling (predominantly grade 2), xerostomia (grades 1 and 2), nausea (grade 2), decreased appetite (grade 2), and vomiting (grade 2). A reduction of greater than 50% in recombinant human thyroid-stimulating hormone–stimulated thyroglobulin levels was observed in 1 of 3 patients (33%) who received 2.5 MBq/kg and 2 of 5 patients (40%) who received 3.5 MBq/kg. At 6 mo, CT-based evaluation showed stable disease (SD) in 9 patients (90%) and progressive disease in 1 patient (10%). 131I SPECT imaging revealed SD in the only patient who received 1.25 MBq/kg. Of the 3 patients treated with 2.5 MBq/kg, a partial response was seen in 1 patient (33%) and SD in 2 patients (67%). Of the 5 patients who received 3.5 MBq/kg, complete response, partial response, and progressive disease were noted in 1 patient (20%) each, and SD was found in 2 patients (40%). Conclusion: Targeted α-therapy with [211At]NaAt was well tolerated and showed preliminary efficacy in patients with RAI-refractory DTC, supporting further clinical investigations.
