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使用自动化流体平台通过基于异羟肟酸酯柱的方法纯化锆-89(Zr)。

Hydroxamate column-based purification of zirconium-89 (Zr) using an automated fluidic platform.

作者信息

O'Hara Matthew J, Murray Nathaniel J, Carter Jennifer C, Kellogg Cynthia M, Link Jeanne M

机构信息

Nuclear Sciences Division, Pacific Northwest National Laboratory, 902 Battelle Blvd., PO Box 999, Richland, WA 99352, USA.

Nuclear Sciences Division, Pacific Northwest National Laboratory, 902 Battelle Blvd., PO Box 999, Richland, WA 99352, USA.

出版信息

Appl Radiat Isot. 2018 Feb;132:85-94. doi: 10.1016/j.apradiso.2017.10.048. Epub 2017 Nov 22.

Abstract

Zirconium-89 (Zr) is a long-lived (t = 78.4h) positron-emitting isotope that is useful for positron emission tomography (PET) based diagnostic imaging using radiolabeled antibodies. Hydroxamate resin columns are predominantly used for the purification of Zr from cyclotron bombarded Y targets dissolved in strong HCl. Zr is conventionally eluted from the resin in 1M oxalic acid (HCO), a complexant that is conducive to follow-on binding of Zr through a transchelation process to the deferoxamine siderophore. In the present study, we determined that a lower concentration of HCO eluent (0.8M) is adequate to efficiently remove Zr from a column containing 100mg hydroxamate resin. As a result, less buffering agents are needed to be added to the Zr product fraction prior to labeling. A simple automated fluidic system prototype has been developed to perform the steps required for Zr purification using a hydroxamate resin column (column conditioning in HCl, Y target dissolution, dissolved target solution load onto column, column washes using HCl and water, and Zr elution). The system performance was evaluated using several cyclotron bombarded Y targets; Zr product fractions demonstrated excellent chemical recoveries from these targets, with 1.0mL product volumes yielding 89±2% of the column elution peak activity and 84±2% of Zr recovered from the target (at EOB). These results compare favorably with previously published Zr product volumes and yields, despite the lower concentration of HCO eluent employed. Transchelation of resulting Zr product fractions was performed to assess product quality. The effective specific activity (ESA) ranged between 44(7) and 109(22) TBq·mmole, while the bindable metals concentration, a metric introduced for assessing and comparing product purity, ranged between 43(7) and 115(27) nmole·g.

摘要

锆 - 89(Zr)是一种长寿命(半衰期t = 78.4小时)的正电子发射同位素,可用于基于正电子发射断层扫描(PET)的放射性标记抗体诊断成像。异羟肟酸树脂柱主要用于从溶解在浓盐酸中的回旋加速器轰击的钇靶中纯化Zr。传统上,Zr用1M草酸(HCO)从树脂上洗脱,草酸是一种络合剂,有利于通过转螯合过程使Zr与去铁胺铁载体后续结合。在本研究中,我们确定较低浓度的HCO洗脱液(0.8M)足以有效地从含有100mg异羟肟酸树脂的柱中去除Zr。因此,在标记之前,Zr产物馏分中需要添加的缓冲剂更少。已开发出一种简单的自动化流体系统原型,以执行使用异羟肟酸树脂柱进行Zr纯化所需的步骤(在HCl中进行柱调节、钇靶溶解、将溶解的靶溶液加载到柱上、用HCl和水进行柱洗涤以及Zr洗脱)。使用几个回旋加速器轰击的钇靶评估了系统性能;Zr产物馏分显示出从这些靶中具有优异的化学回收率,1.0mL产物体积产生柱洗脱峰活性的89±2%以及从靶中回收的Zr的84±2%(在放化终点)。尽管使用的HCO洗脱液浓度较低,但这些结果与先前发表的Zr产物体积和产率相比仍具有优势。对所得Zr产物馏分进行转螯合以评估产物质量。有效比活(ESA)范围在44(7)至109(22) TBq·mmol之间,而可结合金属浓度(一种用于评估和比较产物纯度的指标)范围在43(7)至115(27) nmol·g之间。

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