²²⁶Ac (t_1/2 = 29.37 h) has been proposed as a theranostic radioisotope leveraging both its diagnostic -emissions and therapeutic α-emissions. ²²⁶Ac emits 158 and 230 keV -photons ideal for quantitative SPECT imaging and acts as an in vivo generator of 4 high-energy α-particles. Because of these nuclear decay properties, ²²⁶Ac has potential to act as a standalone theranostic isotope. In this proof-of-concept study, we evaluated a preclinical ²²⁶Ac-radiopharmaceutical for its theranostic efficacy and present the first ²²⁶Ac-targeted α-therapy study. Methods: ²²⁶Ac was produced at TRIUMF and labeled with the chelator-peptide bioconjugate crown-TATE. [²²⁶Ac]Ac-crown-TATE was selected to target neuroendocrine tumors in male NRG mice bearing AR42J tumor xenografts for SPECT imaging, biodistribution, and therapy studies. A preclinical SPECT/CT scanner acquired quantitative images reconstructed from both the 158 and the 230 keV emissions. Mice in the biodistribution study were euthanized at 1, 3, 5, 24, and 48 h after injection, and internal radiation dosimetry was derived for the tumor and organs of interest to establish appropriate therapeutic activity levels. Mice in the therapy study were administered 125, 250, or 375 kBq treatments and were monitored for tumor size and body condition. Results: We present quantitative SPECT images of the in vivo biodistribution of [²²⁶Ac]Ac-crown-TATE, which showed agreement with ex vivo measurements. Biodistribution studies demonstrated high uptake (>30%IA/g at 5 h after injection) and retention in the tumor, with an estimated mean absorbed dose coefficient of 222 mGy/kBq. [²²⁶Ac]Ac-crown-TATE treatments significantly extended the median survival from 7 d in the control groups to 16, 24, and 27 d in the 125, 250, and 375 kBq treatment groups, respectively. Survival was prolonged by slowing tumor growth, and no weight loss or toxicities were observed. Conclusion: This study highlights the theranostic potential of ²²⁶Ac as a standalone therapeutic isotope in addition to its demonstrated diagnostic capabilities to assess dosimetry in matched ²²⁵Ac-radiopharmaceuticals. Future studies will investigate maximum dose and toxicity to further explore the therapeutic potential of ²²⁶Ac-radiopharmaceuticals.

²²⁶ 元Ac （t_1/2 = 29.37 h） 已被提议作为治疗诊断放射性同位素，利用其诊断发射和治疗性 α 发射。²²⁶ 元Ac 发射 158 和 230 keV 光子，非常适合定量 SPECT 成像，并充当 4 个高能 α 粒子的体内发生器。由于这些核衰变特性，²²⁶Ac 有可能作为独立的治疗诊断同位素。在这项概念验证研究中，我们评估了临床前 ²²⁶Ac 放射性药物的治疗诊断学疗效，并提出了第一个 ²²⁶Ac 靶向 α 疗法研究。方法： 在 TRIUMF 生产 ²²⁶Ac，并用螯合剂-肽生物偶联物冠-TATE 标记。[²²⁶厘米]选择 Ac-crown-TATE 靶向携带 AR42J 肿瘤异种移植物的雄性 NRG 小鼠的神经内分泌肿瘤，用于 SPECT 成像、生物分布和治疗研究。临床前 SPECT/CT 扫描仪获取了从 158 和 230 keV 发射重建的定量图像。在注射后 1 、 3 、 5 、 24 和 48 小时对生物分布研究中的小鼠实施安乐死，并对肿瘤和感兴趣的器官进行内部放射剂量测定，以确定适当的治疗活性水平。治疗研究中的小鼠接受 125 、 250 或 375 kBq 治疗，并监测肿瘤大小和身体状况。结果：我们提供了 [²²⁶Ac]Ac-crown-TATE 体内生物分布的定量 SPECT 图像，显示与离体测量一致。生物分布研究表明，注射后 5 小时高摄取 （>30%IA/g） 和在肿瘤中的保留，估计平均吸收剂量系数为 222 mGy/kBq。 [²²⁶厘米]Ac-crown-TATE 处理将中位生存期分别从对照组的 7 d 延长至 125 、 250 和 375 kBq 处理组的 16 、 24 和 27 d。通过减缓肿瘤生长延长生存期，未观察到体重减轻或毒性。结论：本研究强调了 ²²⁶Ac 作为独立治疗同位素的治疗诊断潜力，此外还证明了其评估匹配的 ²²⁵Ac 放射性药物剂量学的诊断能力。未来的研究将调查最大剂量和毒性，以进一步探索 ²²⁶Ac-放射性药物的治疗潜力。