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In vivo MR tracking of therapeutic microglia to a human glioma model
Author(s) -
Ribot Emeline J.,
Miraux Sylvain,
Konsman Jan P.,
Bouchaud Véronique,
Pourtau Line,
Delville MarieHélène,
Franconi JeanMichel,
Thiaudière Eric,
Voisin Pierre J.
Publication year - 2011
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.1699
Subject(s) - microglia , glioma , in vivo , pathology , rhodamine 123 , fluorescence microscope , cancer research , chemistry , medicine , biology , immunology , fluorescence , inflammation , biochemistry , physics , microbiology and biotechnology , quantum mechanics , multiple drug resistance , antibiotics
A knowledge of the spatial localization of cell vehicles used in gene therapy against glioma is necessary before launching therapy. For this purpose, MRI cell tracking is performed by labeling the cell vehicles with contrast agents. In this context, the goal of this study was to follow noninvasively the chemoattraction of therapeutic microglial cells to a human glioma model before triggering therapy. Silica nanoparticles grafted with gadolinium were used to label microglia. These vehicles, expressing constitutively the thymidine kinase suicide gene fused to the green fluorescent protein gene, were injected intravenously into human glioma‐bearing nude mice. MRI was performed at 4.7 T to track noninvasively microglial accumulation in the tumor. This was followed by microscopy on brain slices to assess the presence in the glioma of the contrast agents, microglia and fusion gene through the detection of silica nanoparticles grafted with tetramethyl rhodamine iso‐thiocyanate, 3,3′‐dioctadecyloxacarbocyanine perchlorate and green fluorescent protein fluorescence, respectively. Finally, gancyclovir was administered systemically to mice. Human microglia were detectable in living mice, with strong negative contrast on T 2 *‐weighted MR images, at the periphery of the glioma only 24 h after systemic injection. The location of the dark dots was identical in MR microscopy images of the extracted brains at 9.4 T. Fluorescence microscopy confirmed the presence of the contrast agents, exogenous microglia and suicide gene in the intracranial tumor. In addition, gancyclovir treatment allowed an increase in mice survival time. This study validates the MR tracking of microglia to a glioma after systemic injection and their use in a therapeutic strategy against glioma. Copyright © 2011 John Wiley & Sons, Ltd.