Examination of the effectiveness of Si-based agent in radiotherapy using the alpha-emitting nuclide astatine

Astatine-211 (²¹¹At), an alpha-emitting nuclide with a 7.2-h half-life, significantly suppresses tumor cell proliferation through high-linear energy transfer radiation. ²¹¹At-labeled molecules act locally and are highly effective against invasive gliomas, which are difficult to target with beta-particle emitters. In addition, as an iodine homolog with similar properties and accumulates in thyroid cancer xenografts expressing the sodium/iodide symporter, thereby significantly suppressing tumor growth and extending survival, ²¹¹At represents a promising treatment for metastatic thyroid cancer resistant to conventional beta radiation therapy with ¹³¹I. However, radionuclide-labeled compounds are degraded by OH radicals, and stabilizers such as ascorbic acid are not always effective, highlighting the need for a new reducing agent. Silicon (Si)-based agent reacts with water to continuously generate hydrogen, which has antioxidant properties. Oral administration of this agent has successfully alleviated oxidative stress-related diseases in mouse models, including Parkinson's disease, ulcerative colitis, and small intestinal ischemia/reperfusion injury. In this study, we evaluated the efficacy of a Si-based agent in 211 At radiotherapy. An in vitro study investigating the synthesis reaction of [²¹¹At]NaAt used in thyroid cancer radiotherapy revealed that samples administered with a combination of ascorbic acid and the Si-based agent promoted the synthesis reaction of [²¹¹At]NaAt than those administered with ascorbic acid alone. Moreover, an in vivo experiment examining the radiotherapeutic effect of [ 211 At]APA on glioma demonstrated that the co-administration of the Si-based agent alleviated tumor development more effectively than the administration of ²¹¹At alone. Further analysis will help determine the optimal co-administration conditions, contributing to the advancement of ²¹¹At radiotherapy.