Longitudinal tracking of human dendritic cells in murine models using magnetic resonance imaging

Ex vivo generated dendritic cells are currently used to induce therapeutic immunity in solid tumors. Effective immune response requires dendritic cells to home and remain in lymphoid organs to allow for adequate interaction with T lymphocytes. The aim of the current study was to detect and track Feridex labeled human dendritic cells in murine models using magnetic resonance imaging. Human dendritic cells were incubated with Feridex and the effect of labeling on dendritic cells immune function was evaluated. Ex vivo dendritic cell phantoms were used to estimate sensitivity of the magnetic resonance methods and in vivo homing was evaluated after intravenous or subcutaneous injection. R2*‐maps of liver, spleen, and draining lymph nodes were obtained and inductively coupled plasma mass spectrometry or relaxometry methods were used to quantify the Feridex tissue concentrations. Correlations between in vivo R2* values and iron content were then determined. Feridex labeling did not affect dendritic cell maturation or function. Phantom results indicated that it was possible to detect 125 dendritic cells within a given slice. Strong correlation between in vivo R2* values and iron deposition was observed. Importantly, Feridex‐labeled dendritic cells were detected in the spleen for up to 2 weeks postintravenous injection. This study suggests that magnetic resonance imaging may be used to longitudinally track Feridex‐labeled human dendritic cells for up to 2 weeks after injection. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.

[1]  Jeff W M Bulte,et al.  In vivo MRI cell tracking: clinical studies. , 2009, AJR. American journal of roentgenology.

[2]  Wei Liu,et al.  Detection and quantification of magnetically labeled cells by cellular MRI. , 2009, European journal of radiology.

[3]  A. Roch,et al.  Magnetic resonance relaxation properties of superparamagnetic particles. , 2009, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[4]  Ru-xiang Xu,et al.  In vivo magnetic resonance tracking of Feridex-labeled bone marrow-derived neural stem cells after autologous transplantation in rhesus monkey , 2009, Journal of Neuroscience Methods.

[5]  R. Sékaly,et al.  Semiquantitation of Mouse Dendritic Cell Migration In Vivo Using Cellular MRI , 2009, Journal of immunotherapy.

[6]  M. Chopp,et al.  Investigation of relationships between transverse relaxation rate, diffusion coefficient, and labeled cell concentration in ischemic rat brain using MRI , 2009, Magnetic resonance in medicine.

[7]  Joseph A Frank,et al.  Magnetic Tagging of Therapeutic Cells for MRI , 2009, Journal of Nuclear Medicine.

[8]  R. Knight,et al.  Detection of migration of locally implanted AC133+ stem cells by cellular magnetic resonance imaging with histological findings , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[9]  Zahi A. Fayad,et al.  Serial in vivo positive contrast MRI of iron oxide‐labeled embryonic stem cell‐derived cardiac precursor cells in a mouse model of myocardial infarction , 2008, Magnetic resonance in medicine.

[10]  Xin Wang,et al.  In vivo MR imaging of magnetically labeled mesenchymal stem cells transplanted into rat liver through hepatic arterial injection. , 2008, Contrast media & molecular imaging.

[11]  Dustin J. Maxwell,et al.  Fluorophore‐Conjugated Iron Oxide Nanoparticle Labeling and Analysis of Engrafting Human Hematopoietic Stem Cells , 2008, Stem cells.

[12]  H. Ueno,et al.  Taming cancer by inducing immunity via dendritic cells , 2007, Immunological reviews.

[13]  Jihwan Song,et al.  In Vivo Tracking of Human Mesenchymal Stem Cells in Experimental Stroke , 2007, Cell transplantation.

[14]  R. Steinman,et al.  Taking dendritic cells into medicine , 2007, Nature.

[15]  P. Walczak,et al.  Applicability and limitations of MR tracking of neural stem cells with asymmetric cell division and rapid turnover: The case of the Shiverer dysmyelinated mouse brain , 2007, Magnetic resonance in medicine.

[16]  Hamid Soltanian-Zadeh,et al.  Quantification of superparamagnetic iron oxide (SPIO)‐labeled cells using MRI , 2007, Journal of magnetic resonance imaging : JMRI.

[17]  Z. Fayad,et al.  Feasibility of in vivo identification of endogenous ferritin with positive contrast MRI in rabbit carotid crush injury using GRASP , 2006, Magnetic resonance in medicine.

[18]  Z. Fayad,et al.  Clearance of Iron Oxide Particles in Rat Liver: Effect of Hydrated Particle Size and Coating Material on Liver Metabolism , 2006, Investigative radiology.

[19]  J. Frank,et al.  Cellular magnetic resonance imaging: current status and future prospects , 2006, Expert review of medical devices.

[20]  Kathryn Sharer,et al.  In vivo detection of single cells by MRI , 2006, Magnetic resonance in medicine.

[21]  Zahi A Fayad,et al.  Gradient echo acquisition for superparamagnetic particles with positive contrast (GRASP): Sequence characterization in membrane and glass superparamagnetic iron oxide phantoms at 1.5T and 3T , 2006, Magnetic resonance in medicine.

[22]  A. Arbab,et al.  Labeling of cells with ferumoxides–protamine sulfate complexes does not inhibit function or differentiation capacity of hematopoietic or mesenchymal stem cells , 2005, NMR in biomedicine.

[23]  Arend Heerschap,et al.  Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy , 2005, Nature Biotechnology.

[24]  A. Palucka,et al.  Dendritic cells as therapeutic vaccines against cancer , 2005, Nature Reviews Immunology.

[25]  Alan P Koretsky,et al.  Sizing it up: Cellular MRI using micron‐sized iron oxide particles , 2005, Magnetic resonance in medicine.

[26]  Nicolas Grenier,et al.  In vivo MR imaging of intravascularly injected magnetically labeled mesenchymal stem cells in rat kidney and liver. , 2004, Radiology.

[27]  A. Bjørnerud,et al.  Long‐term imaging effects in rat liver after a single injection of an iron oxide nanoparticle based MR contrast agent , 2004, Journal of magnetic resonance imaging : JMRI.

[28]  P. Schuler,et al.  Effect of physical activity on the production of specific antibody in response to the 1998-99 influenza virus vaccine in older adults. , 2003, The Journal of sports medicine and physical fitness.

[29]  Jeff W M Bulte,et al.  In Vivo Magnetic Resonance Tracking of Magnetically Labeled Cells after Transplantation , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[30]  Gerold Schuler,et al.  Dendritic Cells as Vectors for Therapy , 2001, Cell.

[31]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[32]  A. Roch,et al.  Transverse relaxivity of particulate MRI contrast media: From theories to experiments , 1991, Magnetic resonance in medicine.