Automated Tracking of Nanoparticle-labeled Melanoma Cells Improves the Predictive Power of a Brain Metastasis Model

Abstract

Biologic and therapeutic advances in melanoma brain metastasis are hampered by the paucity of reproducible and predictive animal models. In this work, we developed a robust model of brain metastasis that empowers quantitative tracking of cellular dissemination and tumor progression. Human melanoma cells labeled with superparamagnetic iron oxide nanoparticles (SPION) were injected into the left cardiac ventricle of mice and visualized by MRI. We showed that SPION exposure did not affect viability, growth, or migration in multiple cell lines across several in vitro assays. Moreover, labeling did not impose changes in cell-cycle distribution or apoptosis. In vivo, several SPION-positive cell lines displayed similar cerebral imaging and histologic features. MRI-based automated quantification of labeled cells in the brain showed a sigmoid association between metastasis frequency and doses of inoculated cells. Validation of this fully automated quantification showed a strong correlation with manual signal registration (r 2 ¼ 0.921, P < 0.001) and incidence of brain metastases (r 2 ¼ 0.708, P < 0.001). Metastasis formation resembled the pattern seen in humans and was unaffected by SPION labeling (histology; tumor count, P ¼ 0.686; survival, P ¼ 0.547). In summary, we present here a highly reproducible animal model that can improve the predictive value of mechanistic and therapeutic studies of melanoma brain metastasis. Cancer Res; 73(8); 2445-56. Ó2013 AACR.

EGFR-targeted delivery of DOX-loaded Fe₃O₄@polydopamine multifunctional nanocomposites for MRI and antitumor chemo-photothermal therapy

“…1,2 Magnetic Fe 3 O 4 nanoparticles (NPs) is one of the inorganic-based nanomaterials approved for clinical use, which showed great biocompatibility and has attracted significant attention due to their unique characteristics such as magnetic resonance imaging (MRI) response to an external magnetic field. 3,4 Later, many biocompatible polymers, including chitosan, polyethylene glycol (PEG), and dextran, have been used to be coated in Fe 3 O 4 NPs in order to further improve the properties of Fe 3 O 4 NPs. [5][6][7] As a major pigment of naturally occurring melanin, 8 polydopamine (PDA) is highly biocompatible and biodegradable.…”

Applications of nanotechnology for melanoma treatment, diagnosis, and theranostics

“…Nanotechnology has been used to track the injected cells. 125 Melanoma cells were labeled with superparamagnetic iron oxide nanoparticles and visualized by MRI. This technique contributes to the establishment of a reproducible and predictable metastasis model and could be useful for the prediction of therapeutic outcomes.…”

High-Resolution Mri and Nanoparticles: the Future of Brain Imaging

“…In this model where human breast cancer cells are labeled with MPIOs prior to their intracardiac injection in mice they demonstrated that some cancer cells proliferate, lose the iron label and form brain metastases, while other cells retain the label and persist in the brain as small regions of signal void. More recently, Sundstrøm et al used a similar model of melanoma metastasis with intracardiac delivery of several lines of SPIO-labeled human melanoma to develop a fully automated method to quantify cancer cell delivery to the brain (Figure 4) [61]. Their signal-detection algorithm represents a novel and reproducible method to assess iron-labeled cell dissemination and serves as a useful tool for spatial and temporal monitoring of tumor progression.…”

“…As previously mentioned, the larger size of iron nanoparticles, such as ferumoxytol compared with Gd-based agents, such as gadoteridol, means that ferumoxytol does not extravasate from tumor-associated vasculature regardless of tumor permeability [15]. Unlike Reproduced with permission from [61].…”