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

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

doi:10.14440/jbm.2021.356

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

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

Authors

Natasha N Knier^{1

2}, Veronica P Dubois^{1

2}, Yuanxin Chen², John A Ronald^{1

2

3}, Paula J Foster^{1

2}

Affiliations

¹ Department of Medical Biophysics, Western University, London, Ontario, Canada.
² Imaging Laboratories, Robarts Research Institute, London, Ontario, Canada.
³ Lawson Health Research Institute, London, Ontario, Canada.

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^-/- (n = 5) mice Received injections of 1 × 10⁶ 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. In vivo 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.

Keywords: bioluminescence imaging; breast cancer; cellular imaging; magnetic particle imaging; patient-derived xenografts.