Cell-based therapies—such as stem-cell-based regenerative medicine and adoptive T-cell transfer—have great potential, with the technology for isolation, in vitro expansion, and storage and manufacturing of potentially therapeutic cells having advanced substantially over the last decade. The advent of T-cell-based therapeutics, including chimeric antigen receptor T-cells (CAR T-cells) targeting cancer, has acutely intensified the field of cell therapeutics.

One major challenge that may limit translation and approval of cell-based therapies is the ability to detect and track cells in the body after administration. This is critical for assessing properties of in vivo viability, appropriate cell targeting and persistence of the T-cells following administration. Many of these same factors will drive efficacy, as well as the potential for off-target toxicity. Non-invasive imaging is addressing this hurdle through in vitro image reporter cell labeling and associated image-based tracking of administered cells.

 

Cutting-edge Therapies Need Innovative Technologies

Building on MI’s heritage at the forefront of imaging technology and preclinical research, we conduct MRI-based cell biodistribution studies with therapeutic stem cells and CAR T-cell therapies.

 

Quantification of Cell Biodistribution Non-invasively Using MRI

MI has been validating MRI protocols for cell detection via labeling with MRI-detectable particles. MRI cell detection has typically been based on either super paramagnetic iron oxide (SPIO) that creates significant signal perturbation in proton MRI, or 19F-based detection using 19F MRI. 19F MRI-based cell biodistribution has the important benefit of the detected signal correlating directly with cell concentration, and this is facilitated by the lack of 19F background in the body—making the method highly exact.

The first report demonstrating 19F MRI-based cell tracking in the clinic was recently published by Ahrens and colleagues.[1] Methods based on cell infecting organelles that create intracellular SPIO particles are also in development, with a key advantage being the ability for these organelles to replicate with cells, precluding dilution of the label as the therapeutic cells divide.

In all cases, therapeutic cells are cultured in vitro with SPIO, 19F reagents, or organelles and manipulated if needed to promote labeling. After confirming key properties are unchanged, the labeled cells can be detected using standard MRI protocols, leading to maps of cell biodistribution that can be overlaid on high-resolution anatomical images. These maps can be acquired repeatedly over time in order to quantify cell viability, targeting, tissue residence and engraftment, clearance pathways, and kinetics, helping to ensure the success of future cell therapies.

[1] Ahrens ET et al, Clinical cell therapy imaging using a perfluorocarbon tracer and fluorine-19 MRI, Magn Reson Med 72(6): pp1,696-1,701, 2014. Visit: www.ncbi.nlm.nih.gov/pubmed/25241945