用于放射性药物目的的 89Zr 溶液的制备：制剂、放射化学纯度、稳定性和生物分布之间的关系。

Preparation of Zirconium-89 Solutions for Radiopharmaceutical Purposes: Interrelation Between Formulation, Radiochemical Purity, Stability and Biodistribution.

机构信息

State Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya str., bld. 46; 123182 Moscow, Russia.

Lomonosov Moscow State University, GSP-1, Leninskie Gory, 119991 Moscow, Russia.

出版信息

Molecules. 2019 Apr 18;24(8):1534. doi: 10.3390/molecules24081534.

DOI:10.3390/molecules24081534

PMID:31003494

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6514948/

Abstract

Zirconium-89 is a promising radionuclide for nuclear medicine. The aim of the present work was to find a suitable method for obtaining zirconium-89 solutions for radiopharmaceutical purposes. For this purpose, the ion exchange behavior of zirconium-89 solutions was studied. Radio-TLC (thin layer chromatography) and biodistribution studies were carried out to understand speciation of zirconium-89 complexes and their role in the development of new radiopharmaceuticals. Three methods of zirconium-89 isolation were studied using ZR (hydroxamate) and Chelex-100 resins. It was found that ZR-resin alone is not enough to obtain stable zirconium-89 formulations. An easy and effective method of reconstitution of [Zr]Zr-oxalate to [Zr]Zr-citrate using Chelex-100 resin was developed. Developed procedures allow obtaining [Zr]Zr-oxalate (in 0.1 M sodium oxalate solution) and [Zr]Zr-citrate (in 0.1-1.0 M sodium citrate solution). These solutions are perfectly suitable and convenient for radiopharmaceutical purposes. Our results prove [Zr]Zr-citrate to be advantageous over [Zr]Zr-oxalate. During evaluation of speciation of zirconium-89 complexes, a new TLC method was developed, since it was proved that there is no comprehensive method for analysis or zirconium-89 preparations. The new method provides valuable insights about the content of "active" ionic form of zirconium-89. The interrelation of the chromatographic behavior of zirconium-89 preparations and their biodistribution was studied.

摘要

锝-89 是一种很有前途的核医学放射性核素。本工作的目的是找到一种合适的方法来获得用于放射性药物的锝-89 溶液。为此，研究了锝-89 溶液的离子交换行为。进行了放射性 TLC（薄层层析）和生物分布研究，以了解锝-89 配合物的形态及其在新型放射性药物开发中的作用。使用 ZR（羟肟酸）和 Chelex-100 树脂研究了三种锝-89 分离方法。结果发现，单独使用 ZR 树脂不足以获得稳定的锝-89 制剂。开发了一种使用 Chelex-100 树脂将[Zr]Zr-草酸盐重新组成[Zr]Zr-柠檬酸盐的简单有效的方法。开发的程序允许获得[Zr]Zr-草酸盐（在 0.1 M 草酸钠溶液中）和[Zr]Zr-柠檬酸盐（在 0.1-1.0 M 柠檬酸钠溶液中）。这些溶液非常适合用于放射性药物。我们的结果证明[Zr]Zr-柠檬酸盐优于[Zr]Zr-草酸盐。在评估锝-89 配合物的形态时，开发了一种新的 TLC 方法，因为已经证明没有用于分析或锝-89 制剂的综合方法。该新方法提供了关于“活性”锝-89 离子形式含量的有价值的见解。研究了锝-89 制剂的色谱行为与其生物分布之间的关系。