Hossein Nejadnik1, Prachi Pandit2, Olga Lenkov1, Arian Pourmehdi Lahiji1, Ketan Yerneni1, Heike E Daldrup-Link3,4. 1. Pediatric Molecular Imaging Program in the Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of Medicine, 725 Welch Rd, Rm 1665, Stanford, CA, 94305-5654, USA. 2. Magnetic Insight Inc, Alameda, CA, USA. 3. Pediatric Molecular Imaging Program in the Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of Medicine, 725 Welch Rd, Rm 1665, Stanford, CA, 94305-5654, USA. H.E.Daldrup-Link@stanford.edu. 4. Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. H.E.Daldrup-Link@stanford.edu.
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.
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.
Authors: Jeong Hyun; Monica Grova; Hossein Nejadnik; David Lo; Shane Morrison; Daniel Montoro; Michael Chung; Andrew Zimmermann; Graham G Walmsley; Min Lee; Heike Daldrup-Link; Derrick C Wan; Michael T Longaker Journal: Stem Cells Transl Med Date: 2013-08-09 Impact factor: 6.940
Authors: Bo Zheng; Elaine Yu; Ryan Orendorff; Kuan Lu; Justin J Konkle; Zhi Wei Tay; Daniel Hensley; Xinyi Y Zhou; Prashant Chandrasekharan; Emine U Saritas; Patrick W Goodwill; John D Hazle; Steven M Conolly Journal: Mol Imaging Biol Date: 2017-06 Impact factor: 3.488
Authors: Nikolaos Panagiotopoulos; Robert L Duschka; Mandy Ahlborg; Gael Bringout; Christina Debbeler; Matthias Graeser; Christian Kaethner; Kerstin Lüdtke-Buzug; Hanne Medimagh; Jan Stelzner; Thorsten M Buzug; Jörg Barkhausen; Florian M Vogt; Julian Haegele Journal: Int J Nanomedicine Date: 2015-04-22