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

Abstract

There is momentum towards implementing patient-derived xenograft models (PDX) in cancer research to reflect the histopathology, tumour behavior, and metastatic properties observed in the original tumour. These models are more predictive of clinical outcomes and are superior to cell lines for preclinical drug evaluation and therapeutic strategies. 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 metastases and validate this method with imaging during tumour development.Luciferase expressing human breast cancer PDX cells (F2-7) were successfully labeled after incubation with micron-sized iron oxide particles (MPIO; 25 μg Fe/mL). 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 tumour development. MPI revealed decreasing signal in the tumours and increasing signal in the liver region over time.Here, we demonstrate the first application of MPI to monitor the growth of a PDX MFP tumour. To accomplish this, we also demonstrate 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.

Magnetic particle imaging: tracer development and the biomedical applications of a radiation-free, sensitive, and quantitative imaging modality

“…Knier et al demonstrated the first method for the efficient iron-labelling of PDX cells, which was also the first successful iron-labelling of breast cancer cells derived from patient brain metastases. 271 Utilising bioluminescence imaging (BLI) to evaluate cell viability, and MPI for detection and quantification of SPION content, they demonstrated sensitive longitudinal tracking of pre-labelled F2–7 PDX cells with MPIOs, where the signals indicate cell viability and tumor proliferation.…”