Biology subjects

Knier, N. N.

Publications and source records attributed to Knier, N. N..

2 recordsLinked to original sources

bioRxiv2021

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

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 g Fe/mL). NOD/SCID/ILIIrg-/- (n=5) mice received injections of 1x106 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.

biophysics↗

bioRxiv2020

Comparing the fate of brain metastatic breast cancer cells in different immune compromised mice with cellular magnetic resonance imaging

Metastasis is the leading cause of mortality in breast cancer patients, with brain metastases becoming increasingly prevalent. Studying this disease is challenging due to the limited experimental models and methods available. Here, we used iron-based cellular MRI to track the fate of a mammary carcinoma cell line (MDA-MB-231-BR) in vivo to characterize the growth of brain metastases in the nude and severely immune-compromised NOD/SCID/ILIIrg-/- (NSG) mouse. Nude and NSG mice received injections of iron-labeled MDA-MB-231-BR cells. Images were acquired with a 3T MR system and assessed for signal voids and metastases. The percentage of signal voids and the number and volume of metastases were quantified. Ex vivo imaging of the liver, histology, and immunofluorescence labeling was performed. On day 0, iron-labeled cells were visualized as signal voids throughout the brain. The percentage of voids decreased significantly between day 0 and endpoint. At endpoint, there was no difference in the number of brain metastases or tumour burden in NSG mice compared to nudes. Tumour volumes in nude mice were significantly larger than in NSG mice. Body images indicated that the NSG mice had metastases in the liver, lungs, and lymph nodes. Characterization of the NSG and nude mouse is necessary to study breast cancer brain metastasis in vivo. Here, we show that the 231BR cell line grew differently in NSG mice compared to nude mice. This work demonstrates the role that imaging can play toward credentialing these models that cannot be done with other in vitro or histopathologic methods alone.

biophysics↗