Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, UK.
Lungs for Living Research Centre, UCL Respiratory, Division of Medicine, University College London, London, UK.
Stem Cell Res Ther. 2020 Jun 26;11(1):256. doi: 10.1186/s13287-020-01770-z.
MSCTRAIL is a cell-based therapy consisting of human allogeneic umbilical cord-derived MSCs genetically modified to express the anti-cancer protein TRAIL. Though cell-based therapies are typically designed with a target tissue in mind, delivery is rarely assessed due to a lack of translatable non-invasive imaging approaches. In this preclinical study, we demonstrate Zr-oxine labelling and PET-CT imaging as a potential clinical solution for non-invasively tracking MSCTRAIL biodistribution. Future implementation of this technique should improve our understanding of MSCTRAIL during its evaluation as a therapy for metastatic lung adenocarcinoma.
MSCTRAIL were radiolabelled with Zr-oxine and assayed for viability, phenotype, and therapeutic efficacy post-labelling. PET-CT imaging of Zr-oxine-labelled MSCTRAIL was performed in a mouse model of lung cancer following intravenous injection, and biodistribution was confirmed ex vivo.
MSCTRAIL retained the therapeutic efficacy and MSC phenotype in vitro at labelling amounts up to and above those required for clinical imaging. The effect of Zr-oxine labelling on cell proliferation rate was amount- and time-dependent. PET-CT imaging showed delivery of MSCTRAIL to the lungs in a mouse model of lung cancer up to 1 week post-injection, validated by in vivo bioluminescence imaging, autoradiography, and fluorescence imaging on tissue sections.
Zr-oxine labelling and PET-CT imaging present a potential method of evaluating the biodistribution of new cell therapies in patients, including MSCTRAIL. This offers to improve understanding of cell therapies, including mechanism of action, migration dynamics, and inter-patient variability.
MSCTRAIL 是一种基于细胞的疗法，由经过基因修饰表达抗癌蛋白 TRAIL 的人同种异体脐带来源 MSC 组成。尽管细胞疗法通常针对目标组织进行设计，但由于缺乏可转化的非侵入性成像方法，因此很少评估其输送情况。在这项临床前研究中，我们展示了 Zr-oxine 标记和 PET-CT 成像作为一种潜在的临床解决方案，用于非侵入性追踪 MSCTRAIL 的生物分布。未来实施这项技术应能提高我们对 MSCTRAIL 的理解，因为它正在作为治疗转移性肺腺癌的一种疗法进行评估。
用 Zr-oxine 对 MSCTRAIL 进行放射性标记，并在标记后评估其活力、表型和治疗效果。在肺癌小鼠模型中进行静脉注射后，进行 Zr-oxine 标记的 MSCTRAIL 的 PET-CT 成像，并通过离体方法确认生物分布。
MSCTRAIL 在体外保留了治疗功效和 MSC 表型，标记量高达并超过了临床成像所需的量。Zr-oxine 标记对细胞增殖率的影响与量和时间有关。PET-CT 成像显示，在肺癌小鼠模型中，MSCTRAIL 可递送至肺部，在注射后 1 周内通过体内生物发光成像、放射性自显影和组织切片荧光成像进行验证。
Zr-oxine 标记和 PET-CT 成像提供了一种潜在的方法，可以评估新的细胞疗法在患者中的生物分布，包括 MSCTRAIL。这有助于提高对细胞疗法的理解，包括作用机制、迁移动力学和患者间变异性。
