Astatine-211 (²¹¹At) has emerged as a promising radionuclide for targeted alpha therapy of cancer by virtue of its favorable nuclear properties. However, the limited in vivo stability of ²¹¹At-labeled radiopharmaceuticals remains a major challenge. This review provides a comprehensive overview of the current strategies for ²¹¹At radiolabeling, including nucleophilic and electrophilic substitution reactions, as well as the recent advances in the development of novel bifunctional coupling agents and labeling approaches to enhance the stability of ²¹¹At-labeled compounds. The preclinical and clinical applications of ²¹¹At-labeled radiopharmaceuticals, including small molecules, peptides, and antibodies, are also discussed. Looking forward, the identification of new molecular targets, the optimization of ²¹¹At production and quality control methods, and the continued evaluation of ²¹¹At-labeled radiopharmaceuticals in preclinical and clinical settings will be the key to realizing the full potential of ²¹¹At-based targeted alpha therapy. With the growing interest and investment in this field, ²¹¹At-labeled radiopharmaceuticals are poised to play an increasingly important role in future cancer treatment.

Hydrogen-rich water (HRW) has shown neuroprotective effects in acute brain injury, but its role in chronic radiation-induced brain injury (RIBI) remains unclear. This study investigated the long-term efficacy of HRW in mitigating cognitive impairment and neuronal damage caused by chronic RIBI. Fifty male Sprague Dawley rats were randomly divided into five groups: control, irradiation (IR), IR with memantine, IR with HRW, and IR with combined treatment. All but the control group received 20 Gy whole-brain X-ray irradiation, followed by daily interventions for 60 days. Behavioral assessments, histopathological analyses, oxidative stress measurements, ¹⁸F-FDG PET/CT imaging, transcriptomic sequencing, RT-qPCR, Western blot, and serum ELISA were performed. HRW significantly improved anxiety-like behavior, memory, and learning performance compared to the IR group. Histological results revealed that HRW reduced neuronal swelling, degeneration, and loss and enhanced dendritic spine density and neurogenesis. PET/CT imaging showed increased hippocampal glucose uptake in the IR group, which was alleviated by HRW treatment. Transcriptomic and molecular analyses indicated that HRW modulated key genes and proteins, including CD44, CD74, SPP1, and Wnt1, potentially through the MIF, Wnt, and SPP1 signaling pathways. Serum CD44 levels were also lower in treated rats, suggesting its potential as a biomarker for chronic RIBI. These findings demonstrate that HRW can alleviate chronic RIBI by preserving neuronal structure, reducing inflammation, and enhancing neuroplasticity, supporting its potential as a therapeutic strategy for radiation-induced cognitive impairment.