Paula J. Foster

Background: Preclinical cell tracking is enhanced with a multimodal imaging approach. Bioluminescence imaging (BLI) is a highly sensitive optical modality that relies on engineering cells to constitutively express a luciferase gene. Magnetic particle imaging (MPI) is a newer imaging modality that directly detects superparamagnetic iron oxide (SPIO) particles used to label cells. Here, we compare BLI and MPI for imaging cells in vitro and in vivo. Methods: Mouse 4T1 breast carcinoma cells were transduced to express firefly luciferase, labeled with SPIO (ProMag), and imaged as cell samples after subcutaneous injection into mice. Results: For cell samples, the BLI and MPI signals were strongly correlated with cell number. Both modalities presented limitations for imaging cells in vivo. For BLI, weak signal penetration, signal attenuation, and scattering prevented the detection of cells for mice with hair and for cells far from the tissue surface. For MPI, background signals obscured the detection of low cell numbers due to the limited dynamic range, and cell numbers could not be accurately quantified from in vivo images. Conclusions: It is important to understand the shortcomings of these imaging modalities to develop strategies to improve cellular detection sensitivity.

Preclinical cell tracking is enhanced with a multimodal imaging approach. Bioluminescence imaging (BLI) is a highly sensitive optical modality which relies on engineering cells to constitutively express a luciferase gene. Magnetic particle imaging (MPI) is a newer imaging modality which directly detects superparamagnetic iron oxide (SPIO) particles used to label cells. Here, we compare BLI and MPI for imaging cells in vitro and in vivo. Mouse 4T1 breast carcinoma cells were transduced to express firefly luciferase, labeled with SPIO (ProMag) and imaged as cell samples and after subcutaneous injection into mice. For cell samples, the BLI and MPI signals were strongly correlated with cell number. Both modalities presented limitations for imaging cells in vivo. For BLI, weak signal penetration, signal attenuation and scattering prevented detection of cells for mice with hair and for cells far from the tissue surface. For MPI, background signals obscured the detection of low cell numbers due to the limited dynamic range and cell number could not be accurately quantified from in vivo images. It is important to understand the shortcomings of these imaging modalities to develop strategies to improve cellular detection sensitivity.

Magnetic particle imaging (MPI) provides hotspot tracking and direct quantification of superparamagnetic iron oxide nanoparticle (SPIO)-labelled cells. Bioluminescence imaging (BLI) with the luciferase reporter gene Akaluc can provide complementary information on cell viability. Thus, we explored combining these technologies to provide a more holistic view of cancer cell fate in mice. Akaluc-expressing 4T1Br5 cells were labelled with the SPIO Synomag-D and injected into the mammary fat pads (MFP) of four nude mice. BLI was performed on days 0, 6 and 13, and MPI was performed on days 1, 8 and 14. Ex vivo histology and fluorescence microscopy of MFP and a potential metastatic site was conducted. The BLI signal in the MFP increased significantly from day 0 to day 13 (p < 0.05), mirroring tumor growth. The MPI signal significantly decreased from day 1 to day 14 (p < 0.05) due to SPIO dilution in proliferating cells. Both modalities detected secondary metastases; however, they were visualized in different anatomical regions. Akaluc BLI complemented MPI cell tracking, allowing for longitudinal measures of cell viability and sensitive detection of distant metastases at different locations. We predict this multimodal imaging approach will help to evaluate novel therapeutics and give a better understanding of metastatic mechanisms.