Combining perfluorocarbon and superparamagnetic iron‐oxide cell labeling for improved and expanded applications of cellular MRI

Abstract

Purpose The ability to detect the migration of cells in living organisms is fundamental in understanding biological processes and important for the development of novel cell-based therapies to treat disease. MRI can be used to detect the migration of cells labeled with superparamagnetic iron-oxide (SPIO) or perfluorocarbon (PFC) agents. In this study, we explored combining these two cell-labeling approaches to overcome current limitations and enable new applications for cellular MRI. Methods We characterized 19F-NMR relaxation properties of PFC-labeled cells in the presence of SPIO and imaged cells both ex vivo and in vivo in a rodent inflammation model to demonstrate selective visualization of cell populations. Results We show that with UTE3D, RARE and FLASH 19F images one can uniquely identify PFC-labeled cells, co-localized PFC- and SPIO-labeled cells, and PFC/SPIO co-labeled cells. Conclusion This new methodology has the ability to improve and expand applications of MRI cell tracking. Combining PFC and SPIO strategies can potentially provide a method to quench PFC signal transferred from dead cells to macrophages, thereby eliminating false positives. In addition, combining these techniques could also be used to track two cell types simultaneously and probe cell-cell proximity in vivo with MRI.

Application of dual19F and iron cellular MRI agents to track the infiltration of immune cells to the site of a rejected stem cell transplant

“…More 19 F signal quenching was observed when both agents were administered simultaneously (colabeled). Quenching was also observed for colocalized cells in gradient‐echo fast low angle shot images, but not in spin‐echo rapid acquisition with relaxation enhancement images . These important observations set the stage for the work that we present here in a mouse model of stem cell transplantation and rejection.…”

“…Quenching of the 19 F signal was first reported in a study by Hitchens et al that explored the quenching of signal when 19 F-labeled cells are colabeled with iron nanoparticles (45). The authors showed that the 19 F T2 was significantly reduced in cells that were labeled with both iron and 19 F, but that iron-labeled cells mixed equally with 19 F-labeled cells did not impact the 19…”

“…For group B, the mean apparent cell number sharply declined between days 0 and 2. This significant decrease reflects the presence of iron‐positive macrophages, which has quenched the 19 F signal from the labeled hMSC . Between days 2 and 14, there was no significant change in apparent cell number, suggesting that the iron‐labeled macrophages persist at the implant site.…”

Cell penetrating peptide functionalized perfluorocarbon nanoemulsions for targeted cell labeling and enhanced fluorine‐19 MRI detection

“…The TATP-F68-PFC nanoemulsion droplets are present intracellularly and appear as clusters of small (~100-200 nm) punctate regions of hyperintensity in micrographs ( Figure 4E,F), along with a few larger PFC deposits (~1 μm) ( Figure 4G,H), presumably coalesced droplets, consistent with previous studies. 29,36 Untreated control cells did not contain these hyperintense features in micrographs ( Figure 4C,D). Similar findings were observed for CAR T cells labeled with TATA-F68-PFC nanoemulsion ( Figure 4I-L).…”

Ferromagnetic resonance in the complex permeability of an Fe3O4-based ferrofluid at radio and microwave frequencies

“…Molday ION is primarily used as an MRI contrast agent (see, for example, Refs. [41][42][43]. All of our permeability measurements were made using 2 mL of the Molday ION suspension.…”