A proof-of-concept study to investigate the radiolabelling of human mesenchymal and hematopoietic stem cells with [89Zr]Zr-Df-Bz-NCS

IF 4.4 Q1 CHEMISTRY, INORGANIC & NUCLEAR
Maryke Kahts, Juanita Mellet, Chrisna Durandt, Kinosha Moodley, Beverley Summers, Thomas Ebenhan, Jan Rijn Zeevaart, Omer Aras, Michael S. Pepper
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Abstract

Background

The transplantation of hematopoietic stem and progenitor cells (HSPCs) or mesenchymal stromal/stem cells (MSCs) for the treatment of a wide variety of diseases has been studied extensively. A challenge with cell-based therapies is that migration to and retention at the target site is often difficult to monitor and quantify. Zirconium-89 (89Zr) is a positron-emitting radionuclide with a half-life of 3.3 days, which allows long-term cell tracking. Para-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) is the chelating agent of choice for 89Zr-cell surface labelling. We utilised a shortened labelling method, thereby avoiding a 30–60-min incubation step for [89Zr]Zr-Df-Bz-NCS chelation, to radiolabel HSPCs and MSCs with zirconium-89.

Results

Three 89Zr-MSC labelling attempts were performed. High labelling efficiencies (81.30 and 87.30%) and relatively good labelling yields (59.59 and 67.00%) were achieved with the use of a relatively larger number of MSCs (4.425 and 3.855 million, respectively). There was no significant decrease in MSC viability after 89Zr-labeling (p = 0.31). This labelling method was also translatable to prepare 89Zr-HSPC; preliminary data from one preparation indicated high 89Zr-HSPC labelling efficiency (88.20%) and labelling yield (71.06%), as well as good HSPC viability after labelling (68.65%).

Conclusions

Successful 89Zr-MSC and 89Zr-HSPC labelling was achieved, which underlines the prospects for in vivo cell tracking studies with positron emission tomography. In vitro investigations with larger sample sizes and preclinical studies are recommended.

用[89Zr]Zr-Df-Bz-NCS 对人类间充质干细胞和造血干细胞进行放射性标记的概念验证研究
背景移植造血干细胞和祖细胞(HSPCs)或间充质基质/干细胞(MSCs)来治疗各种疾病的研究已经非常广泛。以细胞为基础的疗法面临的一个挑战是,向目标部位的迁移和在目标部位的滞留往往难以监测和量化。锆-89(89Zr)是一种正电子发射放射性核素,半衰期为 3.3 天,可用于长期细胞追踪。对异硫氰基苄基去铁胺 B(Df-Bz-NCS)是 89Zr 细胞表面标记的首选螯合剂。我们采用了一种缩短的标记方法,从而避免了[89Zr]Zr-Df-Bz-NCS螯合的 30-60 分钟孵育步骤,用锆-89 对 HSPC 和间充质干细胞进行放射性标记。在使用相对较多的间充质干细胞(分别为 442.5 万和 385.5 万)时,实现了较高的标记效率(81.30% 和 87.30%)和相对较好的标记率(59.59% 和 67.00%)。89Zr标记后,间充质干细胞的活力没有明显下降(p = 0.31)。这种标记方法也可用于制备 89Zr-HSPC;一种制备方法的初步数据表明 89Zr-HSPC 标记效率高(88.20%),标记率高(71.06%),标记后 HSPC 存活率高(68.65%)。建议进行样本量更大的体外研究和临床前研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.20
自引率
8.70%
发文量
30
审稿时长
5 weeks
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