Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy

The success of cellular therapies will depend in part on accurate delivery of cells to target organs. In dendritic cell therapy, in particular, delivery and subsequent migration of cells to regional lymph nodes is essential for effective stimulation of the immune system. We show here that in vivo magnetic resonance tracking of magnetically labeled cells is feasible in humans for detecting very low numbers of dendritic cells in conjunction with detailed anatomical information. Autologous dendritic cells were labeled with a clinical superparamagnetic iron oxide formulation or 111In-oxine and were co-injected intranodally in melanoma patients under ultrasound guidance. In contrast to scintigraphic imaging, magnetic resonance imaging (MRI) allowed assessment of the accuracy of dendritic cell delivery and of inter- and intra-nodal cell migration patterns. MRI cell tracking using iron oxides appears clinically safe and well suited to monitor cellular therapy in humans.

[1]  Roland Martin,et al.  Magnetic resonance imaging of labeled T‐cells in a mouse model of multiple sclerosis , 2004, Annals of neurology.

[2]  Elliot R. McVeigh,et al.  Serial Cardiac Magnetic Resonance Imaging of Injected Mesenchymal Stem Cells , 2003, Circulation.

[3]  W. Oyen,et al.  Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state. , 2003, Cancer research.

[4]  A. Enk,et al.  Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma , 1999, The Journal of experimental medicine.

[5]  J A Frank,et al.  Hepatic hemosiderosis in non‐human primates: Quantification of liver iron using different field strengths , 1997, Magnetic resonance in medicine.

[6]  J A Frank,et al.  Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  E. Gilboa,et al.  Injection of Immature Dendritic Cells into Adjuvant-Treated Skin Obviates the Need for Ex Vivo Maturation 1 , 2003, The Journal of Immunology.

[8]  R Weissleder,et al.  Superparamagnetic iron oxide: clinical application as a contrast agent for MR imaging of the liver. , 1988, Radiology.

[9]  Ralph Weissleder,et al.  Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. , 2003, The New England journal of medicine.

[10]  J. Bulte,et al.  Preparation of magnetically labeled cells for cell tracking by magnetic resonance imaging. , 2004, Methods in enzymology.

[11]  Andy Smith.  Mapping the way , 2002, Trends in Neurosciences.

[12]  R. Weissleder,et al.  Ultrasmall superparamagnetic iron oxide: an intravenous contrast agent for assessing lymph nodes with MR imaging. , 1990, Radiology.

[13]  Chien Ho,et al.  In Vivo Dynamic MRI Tracking of Rat T‐Cells Labeled with Superparamagnetic Iron‐Oxide Particles , 1995, Magnetic resonance in medicine.

[14]  E T Ahrens,et al.  Receptor‐mediated endocytosis of iron‐oxide particles provides efficient labeling of dendritic cells for in vivo MR imaging , 2003, Magnetic resonance in medicine.

[15]  Martin F. Mihm,et al.  Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  K. Scheffler,et al.  Hyperechoes , 2001, Magnetic resonance in medicine.

[17]  R Weissleder,et al.  Superparamagnetic iron oxide: pharmacokinetics and toxicity. , 1989, AJR. American journal of roentgenology.

[18]  Jeff W M Bulte,et al.  Iron oxide MR contrast agents for molecular and cellular imaging , 2004, NMR in biomedicine.

[19]  Peter van Gelderen,et al.  Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells , 2001, Nature Biotechnology.

[20]  H. Fine,et al.  Noninvasive MR imaging of magnetically labeled stem cells to directly identify neovasculature in a glioma model. , 2005, Blood.

[21]  C. Figdor,et al.  Maturation of dendritic cells is a prerequisite for inducing immune responses in advanced melanoma patients. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[22]  R. Weissleder,et al.  In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumors. , 2003, Cancer research.

[23]  R. Kiss,et al.  111In-oxine and 99mTc-HMPAO labelling of antigen-loaded dendritic cells: in vivo imaging and influence on motility and actin content , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[24]  C. Figdor,et al.  Melanocyte lineage-specific antigen gp100 is recognized by melanoma- derived tumor-infiltrating lymphocytes , 1994, The Journal of experimental medicine.

[25]  Ergin Atalar,et al.  In Vivo Magnetic Resonance Imaging of Mesenchymal Stem Cells in Myocardial Infarction , 2003, Circulation.

[26]  Mathias Hoehn,et al.  Monitoring of implanted stem cell migration in vivo: A highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[27]  C. Figdor,et al.  Dendritic cell immunotherapy: mapping the way , 2004, Nature Medicine.

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

[29]  C. Figdor,et al.  Migration of dendritic cell based cancer vaccines: in vivo veritas? , 2005, Current opinion in immunology.

[30]  C. Figdor,et al.  Phenotypical and functional characterization of clinical-grade dendritic cells. , 2005, Methods in molecular medicine.