医用钍基放射性核素发生器系统分离概念验证

Bianca Schacherl, Kiara Maurer, Martin Schäfer, Yvonne Remde, Frank Geyer, Annika Fried, Steffen Alexander Happel, Martina Benešová-Schäfer
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引用次数: 0

摘要

α靶向治疗(TαT)是一种新兴的尖端治疗方法,可用于治疗极具挑战性的转移性癌症患者。重要的是,α粒子发射放射性核素(即所谓的α体内纳米发生器)的供应有限,阻碍了 TαT 在临床环境中的广泛应用。通过替代生产途径,包括直接纯化和重新配制策略,可以有效地规避这一问题。放射性核素发生器在简单、稳健的洗脱策略方面具有巨大的潜力,同时还能满足较高的放射性同位素、放射性核素和放射化学纯度标准。本研究通过使用各种金属替代物进行实验,为 TαT 提供了更多的α 体内纳米发生源,从而向新型分离策略迈出了第一步。在不同的系统中,232Th/natBa 被用作 227Th/223Ra 的放射性核素发生器类似物,232Th/natBa/natLa 被用作 229Th/225Ra/225Ac 的三重类似物。针对 232Th/natBa 系统评估了三种选择性树脂(UTEVA、TEVA、DGA-N)。使用更大直径的色谱柱和 1 周的平衡时间,对性能最好的两种树脂的扰动进行了进一步评估。对于 232Th/natBa/natLa 分离系统,采用并评估了带有两种选择性树脂(TK200、TK101)的组合色谱柱。由此获得的结果为不久的将来在放射性概念验证中采用其他分离策略铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Concept validation of separations for thorium-based radionuclide generator systems for medical application
Targeted alpha therapy (TαT) represents an emerging and cutting-edge treatment option for patients dealing with highly challenging metastatic cancer diseases. Critically, the limited supply of alpha-particle-emitting radionuclides, so-called alpha in vivo nanogenerators, hampers wider utilization of TαT in clinical settings. This could effectively be circumvented by alternative production routes, including straightforward purification and reformulation strategies. Radionuclide generators offering great potential in simple and robust elution strategies can be provided that still adhere to high radioisotopic, radionuclidic, and radiochemical purity criteria. This study takes a first step towards novel separation strategies by providing additional sources of alpha in vivo nanogenerators for TαT through experiments with various metal surrogates. With different systems, 232Th/natBa was used as a radionuclide generator analogue to 227Th/223Ra, and 232Th/natBa/natLa was used as a triplet analogue to 229Th/225Ra/225Ac. Three selective resins (UTEVA, TEVA, DGA-N) were evaluated for the 232Th/natBa system. Two perturbations of the best-performing resin were further evaluated using a larger diameter column and 1 week of equilibration. For the 232Th/natBa/natLa separation system, a combined column with two selective resins (TK200, TK101) was employed and evaluated. The results thus obtained pave the way for alternative separation strategies in radioactive proof-of-concept validation in the near future.
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