Author/Authors :
Parkins, Katie M University of Western Ontario - London - Ontario, Canada , Hamilton, Amanda M University of Western Ontario - London - Ontario, Canada , Dubois, Veronica P University of Western Ontario - London - Ontario, Canada , Wong, Suzanne M University of Western Ontario - London - Ontario, Canada , Foster, Paula J University of Western Ontario - London - Ontario, Canada , Ronald, John A University of Western Ontario - London - Ontario, Canada
Abstract :
The combined use of anatomical magnetic resonance imaging (MRI), cellular MRI, and bioluminescence imaging (BLI)
allows for sensitive and improved monitoring of brain metastasis in preclinical cancer models. By using these complementary
technologies, we can acquire measurements of viable single cell arrest in the brain after systemic administration, the clearance and/
or retention of these cells thereafter, the growth into overt tumours, and quantification of tumour volume and relative cancer cell
viability over time. While BLI is very useful in measuring cell viability, some considerations have been reported using cells
engineered with luciferase such as increased tumour volume variation, changes in pattern of metastatic disease, and inhibition of
in vivo tumour growth. Procedures. Here, we apply cellular and anatomical MRI to evaluate in vivo growth difierences between
iron oxide labeled naıve (4T1BR5) and luciferase-expressing (4T1BR5-FLuc-GFP) murine brain-seeking breast cancer cells. Balb/
C mice received an intracardiac injection of 20,000 cells and were imaged with MRI on days 0 and 14. Mice that received 4T1BR5-
FLuc-GFP cells were also imaged with BLI on days 0 and 14. Results. e number of signal voids in the brain (representing ironlabeled cancer cells) on day 0 was significantly higher in mice receiving 4T1BR5 cells compared to mice receiving 4T1BR5-FLucGFP cells (p < 0.0001). Mice that received 4T1BR5 cells also had significantly higher total brain tumour burden and number of
brain metastases than mice that received 4T1BR5-FLuc-GFP cells (p < 0.0001). Conclusions. By employing highly sensitive cellular
MRI tools, we demonstrate that engineered cells did not form tumours as well as their naıve counterparts, which appear to
primarily be due to a reduction in cell arrest. These results indicate that engineering cancer cells with reporter genes may alter their
tropism towards particular organs and highlight another important consideration for research groups that use reporter gene
imaging to track metastatic cancer cell fate in vivo.
