Pozzi Oscar R, Zalutsky Michael R
Department of Radiology, Duke University Medical Center, Durham, NC, 27710, USA.
Nucl Med Biol. 2017 Mar;46:43-49. doi: 10.1016/j.nucmedbio.2016.11.009. Epub 2016 Dec 10.
Alpha particles are radiation of high energy and short range, properties that can lead to radiolysis-mediated complications in labeling chemistry at the high radioactivity levels required for clinical application. In previous papers in this series, we have shown that radiation dose has a profound effect on the astatine species that are present in the labeling reaction and their suitability for the synthesis of N-succinimidyl 3-[At]astatobenzoate. The purpose of this study was to evaluate the effects of adding N-chlorosuccinimide (NCS) to the methanol solution used for initial isolation of At after distillation, a process referred to as At stabilization, on At chemistry after exposure to high radiation doses.
High performance liquid chromatography was used to evaluate the distribution of At species present in methanol in the 500-65,000Gy radiation dose range and the synthesis of SAB from N-succinimidyl 3-(tri-n-butylstannyl)benzoate in the 500-120,000Gy radiation dose range using different At timeactivity combinations under conditions with/without At stabilization.
In the absence of NCS stabilization, a reduced form of astatine, At(2), increased with increasing radiation dose, accounting for about half the total activity by about 15,000Gy, while with stabilization, At(2) accounted for <10% of At activity even at doses >60,000Gy. SAB yields without stabilization rapidly declined with increasing dose, falling to ~20% at about 5000Gy while with stabilization, yields >80% were obtained with At solutions stored for more than 23h and receiving radiation doses >100,000Gy.
Adding NCS to the methanol solution used for initial isolation of At is a promising strategy for countering the deleterious effects of radiolysis on At chemistry.
This strategy could facilitate the ability to perform At labeling at sites remote from its production and at the high activity levels required for clinical applications.
α粒子是一种高能且射程短的辐射，在临床应用所需的高放射性水平下，这些特性可能会在标记化学过程中导致辐射分解介导的并发症。在本系列的前几篇论文中，我们已经表明，辐射剂量对标记反应中存在的砹物种及其对N - 琥珀酰亚胺基3 - [At] 砹苯甲酸酯合成的适用性有深远影响。本研究的目的是评估在蒸馏后用于初始分离砹的甲醇溶液中添加N - 氯代琥珀酰亚胺（NCS）（该过程称为砹稳定化）对高辐射剂量照射后砹化学性质的影响。
使用高效液相色谱法评估在500 - 65,000Gy辐射剂量范围内甲醇中存在的砹物种分布，以及在有/无砹稳定化条件下，使用不同的砹时间 - 活度组合，在500 - 120,000Gy辐射剂量范围内由N - 琥珀酰亚胺基3 - （三正丁基锡基）苯甲酸酯合成SAB的情况。
在没有NCS稳定化的情况下，还原形式的砹At(2)随着辐射剂量的增加而增加，在约15,000Gy时约占总活度的一半，而在有稳定化的情况下，即使在剂量>60,000Gy时，At(2)也占砹活度的<10%。没有稳定化时，SAB产率随着剂量增加迅速下降，在约5000Gy时降至约20%，而在有稳定化的情况下，对于储存超过23小时且接受辐射剂量>100,000Gy的砹溶液，产率>80%。
在用于初始分离砹的甲醇溶液中添加NCS是对抗辐射分解对砹化学性质有害影响的一种有前景的策略。
该策略可以促进在远离其生产地点且在临床应用所需的高活度水平下进行砹标记的能力。
