尽管胰腺导管腺癌 (PDAC) 的治疗选择有限且患者预后不佳，但靶向 α 粒子治疗 (TAT) 代表了该领域的一项有希望的发展。 TAT 显示出治疗转移性癌症的潜力，包括那些对传统治疗产生耐药性的癌症。最吉祥的放射性核素之一是体内 α 发生器 212Pb。与成像兼容的放射性核素 203Pb 相结合，这种治疗诊断匹配是一种有前途的模式，可迅速转化为临床。方法：使用放射性标记的 1,2,4,5-四嗪 (Tz) 示踪剂和反式环辛烯 (TCO) 修饰抗体之间的预靶向方法，对 PDAC 肿瘤异种移植小鼠模型进行成像和放射性铅治疗。对于治疗，3 个队列接受单次施用 1.1、2.2 或 3.7 MBq 的预靶向剂 [212Pb]Pb-DO3A-PEG7-Tz，其中施用的活性水平由剂量分析指导。结果：对治疗组小鼠进行全面评价；观察到极轻微至轻度的肾小管坏死。与此同时，与对照组（5.1 周）相比，最高剂量组（10.7 周）的中位生存期增加了一倍。结论：这项基础研究证明了在 PDAC 中使用 212Pb 进行预靶向 TAT 的可行性和安全性，同时考虑了剂量限制和潜在的副作用。© 2024，核医学和分子影像学会。

Although pancreatic ductal adenocarcinoma (PDAC) is associated with limited treatment options and poor patient outcomes, targeted α-particle therapy (TAT) represents a promising development in the field. TAT shows potential in treating metastatic cancers, including those that have become resistant to conventional treatments. Among the most auspicious radionuclides stands the in vivo α-generator 212Pb. Combined with the imaging-compatible radionuclide 203Pb, this theranostic match is a promising modality rapidly translating into the clinic. Methods: Using the pretargeting approach between a radiolabeled 1,2,4,5-tetrazine (Tz) tracer and a trans-cyclooctene (TCO) modified antibody, imaging and therapy with radiolead were performed on a PDAC tumor xenograft mouse model. For therapy, 3 cohorts received a single administration of 1.1, 2.2, or 3.7 MBq of the pretargeting agent, [212Pb]Pb-DO3A-PEG7-Tz, whereby administered activity levels were guided by dosimetric analysis. Results: The treated mice were holistically evaluated; minimal-to-mild renal tubular necrosis was observed. At the same time, median survival doubled for the highest-dose cohort (10.7 wk) compared with the control cohort (5.1 wk). Conclusion: This foundational study demonstrated the feasibility and safety of pretargeted TAT with 212Pb in PDAC while considering dose limitations and potential adverse effects.© 2024 by the Society of Nuclear Medicine and Molecular Imaging.