EJNMMI radiopharmacy and chemistry · 2026
Redox-driven speciation and colloid formation contribute the in vivo chemistry and organ deposition of Astatine-211.
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Dong Xiaoxu, Li Jiaojiao, Chen Mumei, Zhang Kaiqi, Zhang Xiaozheng, Shan Fengling, Xue Shuai, Li Xiao, Zhang Lan, Cai Huawei, Liu Jiajun, Li Qingnuan
Аннотация
BACKGROUND: Astatine-211 (211At) is a promising radionuclide for targeted alpha therapy (TAT), yet its clinical translation is hindered by poor in vivo stability and pronounced non-target organ accumulation. The fundamental radiochemical mechanisms governing the biodistribution of free 211At remain insufficiently understood, limiting rational radiopharmaceutical design.
RESULTS: Comparative in vivo studies revealed that free 211At and free iodine-131 (131I) initially share similar distribution patterns but diverge markedly thereafter, with 211At exhibiting pronounced accumulation in the stomach, lungs, liver, and spleen. Experimental speciation analyses demonstrated rapid oxidation of At- to cationic intermediates in biological environments, followed by hydrolysis and colloid formation. Ultrafiltration and chromatography confirmed the generation of macromolecular species responsible for hepatosplenic retention. Co-administration of ascorbic acid (AA) partially suppressed abnormal organ uptake, supporting a redox-dependent mechanism. Density functional theory (DFT)-based Pourbaix analysis further corroborated the thermodynamic instability of At- under physiological conditions and predicted the predominance of oxidized and hydrolyzed species.
CONCLUSIONS: These results identify redox-driven speciation and subsequent hydrolysis/aggregation as key chemical processes contributing to the in vivo behavior of free 211At. Understanding and controlling astatine redox chemistry is therefore critical for improving the stability, safety, and translational development of 211At-based radiopharmaceuticals.
RESULTS: Comparative in vivo studies revealed that free 211At and free iodine-131 (131I) initially share similar distribution patterns but diverge markedly thereafter, with 211At exhibiting pronounced accumulation in the stomach, lungs, liver, and spleen. Experimental speciation analyses demonstrated rapid oxidation of At- to cationic intermediates in biological environments, followed by hydrolysis and colloid formation. Ultrafiltration and chromatography confirmed the generation of macromolecular species responsible for hepatosplenic retention. Co-administration of ascorbic acid (AA) partially suppressed abnormal organ uptake, supporting a redox-dependent mechanism. Density functional theory (DFT)-based Pourbaix analysis further corroborated the thermodynamic instability of At- under physiological conditions and predicted the predominance of oxidized and hydrolyzed species.
CONCLUSIONS: These results identify redox-driven speciation and subsequent hydrolysis/aggregation as key chemical processes contributing to the in vivo behavior of free 211At. Understanding and controlling astatine redox chemistry is therefore critical for improving the stability, safety, and translational development of 211At-based radiopharmaceuticals.