Abstract Unwanted targeting of healthy organs caused by the relocation of radionuclides from the target site has been one of the limiting factors in the widespread application of targeted alpha therapy in patient regimens. GdVO4 nanoparticles (NPs) were developed as platforms to encapsulate α-emitting radionuclides 223Ra, 225Ac, and 227Th, and retain their decay daughters at the target site. Polycrystalline GdVO4 NPs with different morphologies and a zircon-type tetragonal crystal structure were obtained by precipitation of GdCl3 and Na3VO4 in aqueous media at room temperature. The ability of GdVO4 crystals to host multivalent ions was initially assessed using La, Cs, Bi, Ba, and Pb as surrogates of the radionuclides under investigation. A decrease in Ba encapsulation was obtained after increasing the concentration of surrogate ions, whereas the encapsulation of La cations in GdVO4 NPs was quantitative (∼100%). Retention of radionuclides was assessed in vitro by dialyzing the radioactive GdVO4 NPs against deionized water. While 227Th was quantitatively encapsulated (100%), a partial encapsulation of 223Ra (∼75%) and 225Ac (>60%) was observed in GdVO4 NPs. The maximum leakage of 221Fr (1st decay daughter of 225Ac) was 55.4 ± 3.6%, whereas for 223Ra (1st decay daughter of 227Th) the maximum leakage was 73.0 ± 4.0%. These results show the potential of GdVO4 NPs as platforms of α-emitting radionuclides for their application in targeted alpha therapy.

中文翻译：

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锆石型钒酸钆纳米颗粒中 225Ac、223Ra、227Th 和衰变子体的封装和保留

摘要 放射性核素从靶位转移引起的对健康器官的不必要靶向一直是靶向 α 疗法在患者治疗方案中广泛应用的限制因素之一。GdVO4 纳米粒子 (NPs) 被开发作为平台来封装 α 发射放射性核素 223Ra、225Ac 和 227Th，并将它们的衰变子体保留在目标位置。通过在室温下在水性介质中沉淀 GdCl3 和 Na3VO4，获得了具有不同形貌和锆石型四方晶体结构的多晶 GdVO4 NPs。GdVO4 晶体承载多价离子的能力最初是使用 La、Cs、Bi、Ba 和 Pb 作为正在研究的放射性核素的替代物进行评估的。增加替代离子的浓度后，Ba 的包封减少，而 La 阳离子在 GdVO4 NPs 中的包封是定量的（~100%）。通过用去离子水透析放射性 GdVO4 NPs，在体外评估放射性核素的保留。虽然 227Th 被定量封装 (100%)，但在 GdVO4 NPs 中观察到 223Ra (~75%) 和 225Ac (>60%) 的部分封装。221Fr（225Ac 的第一个衰变子体）的最大泄漏为 55.4±3.6%，而 223Ra（227Th 的第一个衰变子体）的最大泄漏为 73.0±4.0%。这些结果显示了 GdVO4 NPs 作为 α 发射放射性核素平台在靶向 α 治疗中的应用潜力。在 GdVO4 NPs 中观察到 223Ra（~75%）和 225Ac（>60%）的部分包封。221Fr（225Ac 的第一个衰变子体）的最大泄漏为 55.4±3.6%，而 223Ra（227Th 的第一个衰变子体）的最大泄漏为 73.0±4.0%。这些结果显示了 GdVO4 NPs 作为 α 发射放射性核素平台在靶向 α 治疗中的应用潜力。在 GdVO4 NPs 中观察到 223Ra（~75%）和 225Ac（>60%）的部分包封。221Fr（225Ac 的第一个衰变子体）的最大泄漏为 55.4±3.6%，而 223Ra（227Th 的第一个衰变子体）的最大泄漏为 73.0±4.0%。这些结果显示了 GdVO4 NPs 作为 α 发射放射性核素平台在靶向 α 治疗中的应用潜力。