We recently reported the dose-dependent therapeutic effect of ²¹¹At-NaAt in differentiated thyroid cancer xenograft models. In the present study, we evaluated the radiation-induced toxicity of ²¹¹At-NaAt using detailed hematological, biochemical, and histological analyses. Biodistribution of ²¹¹At-NaAt was measured in normal ICR mice (n = 12), absorbed doses in the major organs were calculated. Groups of ICR mice (n = 60) were injected with 0.1 MBq or 1 MBq of ²¹¹At-NaAt, using saline as the control group (n = 30). Body weight and food intake were followed up for 60 days. Blood cell counts and serum level of biochemical parameters were measured 3, 7, 15, 29, 60 days after injection. Histological analyses of the major organs with hematoxylin and eosin staining were performed. Biodistribution study revealed a high-absorbed dose in the thyroid gland, stomach, bladder, heart, lungs, spleen, kidneys, and testis. The 0.1 MBq group showed no abnormalities. The 1 MBq group showed decreased body weight and food intake. Histological analysis showed atrophy and fibrosis in the thyroid gland, a transient hypospermatogenesis in the testis on day 29 was found in one mouse. Hematological toxicity was mild and transient. The total cholesterol, albumin, and total protein increased with no signs of recovery, which was considered to be caused by hypothyroidism. High-dose administration of ²¹¹At-NaAt showed transient toxicity in the white blood cells and testis without severe hematological or renal toxicity, suggesting its tolerable safety as targeted alpha-therapy for differentiated thyroid cancer in the 1 MBq group.

我们最近报道了在分化的甲状腺癌异种移植模型中²¹¹ At-NaAt的剂量依赖性治疗作用。在本研究中，我们使用详细的血液学，生化和组织学分析评估了²¹¹ At-NaAt的辐射诱导毒性。在正常ICR小鼠（n = 12）中测量了²¹¹ At-NaAt的生物分布，计算了主要器官的吸收剂量。每组ICR小鼠（n = 60）分别注射0.1 MBq或1 MBq的²¹¹At-NaAt，以生理盐水为对照组（n = 30）。对体重和食物摄入进行了60天的随访。注射后3、7、15、29、60天测量血细胞计数和血清生化参数水平。用苏木精和曙红染色对主要器官进行组织学分析。生物分布研究表明，在甲状腺，胃，膀胱，心脏，肺，脾脏，肾脏和睾丸中有高吸收剂量。0.1 MBq组未显示异常。1 MBq组显示体重和食物摄入减少。组织学分析显示甲状腺的萎缩和纤维化，在第29天在一只小鼠的睾丸中发现了短暂的生精减低。血液学毒性是轻微的和短暂的。总胆固醇，白蛋白和总蛋白质增加，没有恢复的迹象，被认为是由甲状腺功能减退引起的。大剂量给药²¹¹ At-NaAt在白细胞和睾丸中显示出短暂的毒性，而没有严重的血液学或肾脏毒性，表明其作为1 MBq组中针对分化型甲状腺癌的靶向α疗法的耐受性安全。