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Characterization of Magneto-Endosymbionts as MRI Cell Labeling and Tracking Agents
Kimberly D Brewer1,2, Ryan Spitler2, Kayla R Lee3
1Biomedical Translational Imaging Centre (BIOTIC), Halifax, Nova Scotia, Canada.
Purpose:
Magneto-endosymbionts (MEs) show promise as living magnetic resonance imaging (MRI) contrast agents for in vivo cell tracking. Here we characterize the biomedical imaging properties of ME contrast agents, in vitro and in vivo.
Procedures:
By adapting and engineering magnetotactic bacteria to the intracellular niche, we are creating magneto-endosymbionts (MEs) that offer advantages relative to passive iron-based contrast agents (superparamagnetic iron oxides, SPIOs) for cell tracking. This work presents a biomedical imaging characterization of MEs including: MRI transverse relaxivity (r 2) for MEs and ME-labeled cells (compared to a commercially available iron oxide nanoparticle); microscopic validation of labeling efficiency and subcellular locations; and in vivo imaging of a MDA-MB-231BR (231BR) human breast cancer cells in a mouse brain.
Results:
At 7T, r 2 relaxivity of bare MEs was higher (250 s-1 mM-1) than that of conventional SPIO (178 s-1 mM-1). Optimized in vitro loading of MEs into 231BR cells yielded 1-4 pg iron/cell (compared to 5-10 pg iron/cell for conventional SPIO). r 2 relaxivity dropped by a factor of ~3 upon loading into cells, and was on the same order of magnitude for ME-loaded cells compared to SPIO-loaded cells. In vivo, ME-labeled cells exhibited strong MR contrast, allowing as few as 100 cells to be detected in mice using an optimized 3D SPGR gradient-echo sequence.
Conclusions:
Our results demonstrate the potential of magneto-endosymbionts as living MR contrast agents. They have r 2 relaxivity values comparable to traditional iron oxide nanoparticle contrast agents, and provide strong MR contrast when loaded into cells and implanted in tissue.
Insights
Magneto-endosymbionts (MEs) show promise as living MRI contrast agents. These engineered bacteria offer comparable MRI performance to iron oxide nanoparticles for in vivo cell tracking.
Area of Science:
- Biomedical Engineering
- Microbiology
- Medical Imaging
Background:
- Magneto-endosymbionts (MEs) are engineered magnetotactic bacteria designed for intracellular applications.
- MEs offer potential advantages over conventional superparamagnetic iron oxide nanoparticles (SPIOs) for cell tracking.
- Characterizing the biomedical imaging properties of MEs is crucial for their clinical translation.
Purpose of the Study:
- To characterize the in vitro and in vivo biomedical imaging properties of magneto-endosymbionts (MEs).
- To evaluate MEs as living magnetic resonance imaging (MRI) contrast agents for cell tracking.
- To compare the performance of MEs with conventional SPIOs.
Main Methods:
- Engineered magnetotactic bacteria to create magneto-endosymbionts (MEs).
- Measured MRI transverse relaxivity (r2) of MEs and ME-labeled cells.
- Validated labeling efficiency and subcellular localization using microscopy.
- Performed in vivo imaging of ME-labeled cancer cells in mouse brains.
Main Results:
- Bare MEs exhibited higher r2 relaxivity (250 s⁻¹ mM⁻¹) than conventional SPIO (178 s⁻¹ mM⁻¹) at 7T.
- ME-labeled cells showed strong MR contrast, enabling detection of as few as 100 cells in vivo.
- r2 relaxivity of MEs decreased by approximately 3-fold upon cellular loading but remained comparable to SPIO-loaded cells.
Conclusions:
- Magneto-endosymbionts show significant potential as living MRI contrast agents.
- MEs demonstrate MRI relaxivity values comparable to traditional iron oxide nanoparticles.
- When loaded into cells, MEs provide strong MR contrast for in vivo imaging applications.
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