Ferumoxytol Can Be Used for Quantitative Magnetic Particle Imaging of Transplanted Stem Cells

Abstract

Purpose: To evaluate, if clinically translatable ferumoxytol nanoparticles can be used for in vivo detection and quantification of stem cell transplants with magnetic particle imaging (MPI). Procedures: Mesenchymal stem cells (MSCs) were labeled with ferumoxytol or ferucarbotran and underwent MPI, magnetic resonance imaging (MRI), Prussian blue staining, and inductively coupled plasma (ICP) spectrometry. Unlabeled, ferumoxytol, and ferucarbotran-labeled MSCs were implanted in calvarial defects of eight mice and underwent MPI, MRI, and histopathology. The iron concentration calculated according to the MPI signal intensity and T2 relaxation times of the three different groups were compared using an analysis of variance (ANOVA) with Bonferroni correction, and a p < 0.05. Results: Compared to unlabeled controls, ferumoxytol- and ferucarbotran-labeled MSC showed significantly increased iron content, MPI signal and MRI signal. The ferumoxytol MPI signal was approximately 4× weaker compared to ferucarbotran at equimolar concentrations (p = 0.0003) and approximately 1.5× weaker for labeled cells when using optimized labeling protocols (p = 0.002). In vivo, the MPI signal of ferumoxytol-labeled MSC decreased significantly between day 1 and day 14 (p = 0.0124). This was confirmed by histopathology where we observed a decrease in Prussian blue stain of MSCs at the transplant site. The MRI signal of the same transplants did not change significantly during this observation period (p = 0.93). Conclusion: Ferumoxytol nanoparticles can be used for in vivo detection of stem cell transplants with MPI and provide quantitative information not attainable with MRI.