Watabe Tadashi
Dept. of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine.
Gan To Kagaku Ryoho. 2022 Aug;49(8):829-834.
Radioactive iodine has long been used clinically for patients with differentiated thyroid cancer. Radioiodine(131I) is used for the ablation of thyroid remnants or treatment of metastatic thyroid cancer. However, some patients with multiple metastases are refractory to repetitive 131I treatment, despite the targeted regions showing sufficient iodine uptake. In such patients, β- particle therapy using 131I is inadequate and another strategy is needed using more effective radionuclide targeting the sodium/iodide symporter(NIS). Astatine(211At)is receiving increasing attention as an α-emitter for targeted radionuclide therapy. 211At is a halogen element with similar chemical properties to iodine. α particles emitted from 211At has higher linear energy transfer as compared to β particles from 131I and exert a better therapeutic effect by inducing DNA double strand breaks and free radical formation. We showed that increase of the radiochemical purity of astatide of 211At solution by addition of ascorbic acid was associated with significantly enhanced uptake of 211At by both normal thyroid tissue and differentiated thyroid cancer cells. The treatment effect of 211At solution in the K1-NIS xenograft model was dose-dependent and was associated with prolonged survival, suggesting the potential applicability of targeted α therapy for the treatment of advanced differentiated thyroid cancer. Thus, targeted α therapy using 211At is highly promising for the treatment of advanced differentiated thyroid cancer. We have already started the clinical trial of 211At-NaAt in Osaka University Hospital since November 2021 after getting the approval by IRB and PMDA investigation. We would like to get the proof of concept that astatine can be used safely and effectively in patients, aiming at the drug approval as a targeted α therapeutic from Japan.
放射性碘长期以来一直用于分化型甲状腺癌患者的临床治疗。放射性碘（131I）用于甲状腺残余组织的消融或转移性甲状腺癌的治疗。然而，一些有多处转移的患者对重复的131I治疗无效，尽管靶向区域显示出足够的碘摄取。在这类患者中，使用131I的β粒子治疗并不充分，需要采用另一种策略，即使用更有效的靶向钠/碘同向转运体（NIS）的放射性核素。砹（211At）作为一种用于靶向放射性核素治疗的α发射体正受到越来越多的关注。211At是一种化学性质与碘相似的卤素元素。与131I发射的β粒子相比，211At发射的α粒子具有更高的线性能量传递，通过诱导DNA双链断裂和自由基形成发挥更好的治疗效果。我们发现，通过添加抗坏血酸提高211At溶液砹化物的放射化学纯度，与正常甲状腺组织和分化型甲状腺癌细胞对211At的摄取显著增加有关。211At溶液在K1-NIS异种移植模型中的治疗效果呈剂量依赖性，且与生存期延长有关，这表明靶向α治疗在晚期分化型甲状腺癌治疗中的潜在适用性。因此，使用211At的靶向α治疗在晚期分化型甲状腺癌的治疗中极具前景。自2021年11月获得机构审查委员会（IRB）批准和日本药品和医疗器械管理局（PMDA）调查通过后，我们已经在大阪大学医院开始了211At-NaAt的临床试验。我们希望获得砹可以在患者中安全有效使用的概念验证，目标是在日本批准其作为一种靶向α治疗药物。
