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一种对患者来源的异种移植细胞进行高效铁标记及细胞成像验证的方法。

A method for the efficient iron-labeling of patient-derived xenograft cells and cellular imaging validation.

作者信息

Knier Natasha N, Dubois Veronica P, Chen Yuanxin, Ronald John A, Foster Paula J

机构信息

Department of Medical Biophysics, Western University, London, Ontario, Canada.

Imaging Laboratories, Robarts Research Institute, London, Ontario, Canada.

出版信息

J Biol Methods. 2021 Sep 3;8(3):e154. doi: 10.14440/jbm.2021.356. eCollection 2021.

Abstract

There is momentum towards implementing patient-derived xenograft models (PDX) in cancer research to reflect the histopathology, tumor behavior, and metastatic properties observed in the original tumor. To study PDX cells preclinically, we used both bioluminescence imaging (BLI) to evaluate cell viability and magnetic particle imaging (MPI), an emerging imaging technology to allow for detection and quantification of iron nanoparticles. The goal of this study was to develop the first successful iron labeling method of breast cancer cells derived from patient brain metsastases and validate this method with imaging during tumor development. The overall workflow of this labeling method is as follows: adherent and non-adherent luciferase expressing human breast cancer PDX cells (F2-7) are dissociated and concurrently labeled after incubation with micron-sized iron oxide particles (MPIO; 25 μg Fe/ml), with labeling validated by cellular imaging with MPI and BLI. In this study, NOD/SCID/ILIIrg ( = 5) mice Received injections of 1 × 10 iron-labeled F2-7 cells into the fourth mammary fat pad (MFP). BLI was performed longitudinally to day 49 and MPI was performed up to day 28. BLI revealed that signal increased over time with tumor development. MPI revealed decreasing signal in the tumors over time. Here, we demonstrate the first application of MPI to monitor the growth of a PDX MFP tumor and the first successful labeling of PDX cells with iron oxide particles. Imaging of PDX cells provides a powerful system to better develop personalized therapies targeting breast cancer brain metastasis.

摘要

在癌症研究中,采用患者来源的异种移植模型(PDX)以反映原发肿瘤中观察到的组织病理学、肿瘤行为和转移特性的趋势正在增强。为了在临床前研究PDX细胞,我们使用生物发光成像(BLI)评估细胞活力,并使用磁粒子成像(MPI),这是一种新兴的成像技术,可用于检测和定量铁纳米颗粒。本研究的目的是开发第一种成功的对源自患者脑转移灶的乳腺癌细胞进行铁标记的方法,并在肿瘤发展过程中通过成像验证该方法。这种标记方法的总体工作流程如下:将贴壁和非贴壁的表达荧光素酶的人乳腺癌PDX细胞(F2-7)解离,并在与微米级氧化铁颗粒(MPIO;25μg Fe/ml)孵育后同时进行标记,通过MPI和BLI细胞成像验证标记。在本研究中,NOD/SCID/ILIIrg(n = 5)小鼠接受将1×10个铁标记的F2-7细胞注射到第四乳腺脂肪垫(MFP)中。纵向进行BLI至第49天,MPI进行至第28天。BLI显示信号随肿瘤发展而随时间增加。MPI显示肿瘤中的信号随时间减少。在这里,我们展示了MPI首次应用于监测PDX MFP肿瘤的生长以及首次成功地用氧化铁颗粒标记PDX细胞。对PDX细胞进行成像提供了一个强大的系统,以更好地开发针对乳腺癌脑转移的个性化疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/306f/8487865/6023dbfdf920/jbm-8-3-e154-g001.jpg

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