不同形式的非共轭砹-211与血清白蛋白的自发关联。

IF 3 4区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Nuclear medicine and biology Pub Date : 2026-03-01 Epub Date: 2026-02-02 DOI:10.1016/j.nucmedbio.2026.109608

Emma Aneheim , Sture Lindegren , Holger Jensen , Tom Bäck

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引用次数: 0

摘要

目的/简介：Astatine-211是一种α粒子发射核素，研究用于播散性癌症的靶向α治疗（TAT）。在以前的研究中，当比较砹化化合物和碘化化合物时，已经观察到血液清除率的差异。这可以解释为游离砹可能在血液中滞留时间较长。本研究考察了体外生理条件下非共轭砹与白蛋白的自发结合，并将其与碘的自发结合进行了比较。此外，评估游离砹的体内血液循环模式，并与碘的对比。材料和方法：将砹溶解于CHCl3中，经干馏、蒸发至干燥，配制成砹溶液。体外评价astastine和碘与白蛋白的关联主要采用一次性色谱柱（PD10和NAP10）和FPLC系统（ÄKTA），在线紫外检测和活性组分收集。采用甲醇沉淀法和放射性薄层色谱法进行分析。实验采用毛BALB/C小鼠（3只/组），分别静脉和腹腔注射阿司他汀，然后依次从尾静脉采血并进行生物分布。结果：与还原形式相比，氧化和未修饰形式的游离砹与白蛋白的结合明显更高、更快，其与白蛋白的结合率为97%。结论：不同形式的未结合砹与白蛋白的结合不同。然而，所有研究形式的游离砹与白蛋白的结合程度远高于碘。这种行为可以解释游离砹相对于碘的血液循环延长的原因。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Spontaneous association of different forms of non-conjugated astatine-211 to serum albumin

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Spontaneous association of different forms of non-conjugated astatine-211 to serum albumin

Aim/introduction

Astatine-211 is one of the alpha-particle emitting nuclides investigated for use within Targeted Alpha Therapy (TAT) of disseminated cancer. In previous studies, a difference in blood clearance has been observed when comparing astatinated compounds with their iodinated counterparts. This has been explained by a potentially prolonged retention in the blood by present free astatine. This study examined the spontaneous binding of non-conjugated astatine to albumin under physiological conditions in vitro and compared it to that of iodine. Additionally, the in vivo blood circulation patterns of free astatine were assessed and contrasted with those of iodine.

Materials and methods

Astatine solutions were formulated following dry distillation and evaporation to dryness of astatine solvated in CHCl₃. In vitro evaluation of astatine and iodine association to albumin was mainly performed using size exclusion chromatography applying both disposable columns (PD10 and NAP10) as well as an FPLC system (ÄKTA) with online UV detection and activity fraction collection. Also methanol precipitation and radio-TLC methods were used for analysis. In vivo evaluation was performed using furry BALB/C mice (3/group) with both i.v. and i.p. injection of astatine, followed by sequential blood sampling from the tail vein and biodistribution.

Results

Oxidized and unmodified forms of free astatine display a significantly higher and more rapid association to albumin in vitro compared to reduced forms, with >97% compared to <25% associated after 10 min. Both the corresponding oxidized and reduced forms of iodine display a very low and slow association to albumin with <5% associated after 40 min. Oxidized, unmodified and reduced astatine show very similar blood profiles over time as well as a similar uptake in biodistribution after 20–22 h following i.p. injection. Upon i.v. injection a larger difference in blood profiles between the species could be observed, which in turn was different compared to the curve obtained after i.p. injection. In addition, an unexpected uptake of astatide in stomach was found. In all cases the blood profile and biodistribution of astatine was significantly different compared to iodine, which displayed a greater and more rapid blood clearance and specific accumulation in thyroid.

Conclusion

Different forms of unbound astatine differ in their association to albumin. However, all investigated forms of free astatine associates to albumin to a much higher degree than iodine. This behavior could explain the prolonged blood circulation of free astatine compared to iodine.

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来源期刊

Nuclear medicine and biology 医学-核医学

CiteScore

6.00

自引率

9.70%

发文量

479

审稿时长

51 days

期刊介绍： Nuclear Medicine and Biology publishes original research addressing all aspects of radiopharmaceutical science: synthesis, in vitro and ex vivo studies, in vivo biodistribution by dissection or imaging, radiopharmacology, radiopharmacy, and translational clinical studies of new targeted radiotracers. The importance of the target to an unmet clinical need should be the first consideration. If the synthesis of a new radiopharmaceutical is submitted without in vitro or in vivo data, then the uniqueness of the chemistry must be emphasized. These multidisciplinary studies should validate the mechanism of localization whether the probe is based on binding to a receptor, enzyme, tumor antigen, or another well-defined target. The studies should be aimed at evaluating how the chemical and radiopharmaceutical properties affect pharmacokinetics, pharmacodynamics, or therapeutic efficacy. Ideally, the study would address the sensitivity of the probe to changes in disease or treatment, although studies validating mechanism alone are acceptable. Radiopharmacy practice, addressing the issues of preparation, automation, quality control, dispensing, and regulations applicable to qualification and administration of radiopharmaceuticals to humans, is an important aspect of the developmental process, but only if the study has a significant impact on the field. Contributions on the subject of therapeutic radiopharmaceuticals also are appropriate provided that the specificity of labeled compound localization and therapeutic effect have been addressed.