In vivo MR tracking of therapeutic microglia to a human glioma model.
NMR Biomed.. 2011-03-08; 24(10): 1361-1368
DOI: 10.1002/nbm.1699
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1. NMR Biomed. 2011 Dec;24(10):1361-8. doi: 10.1002/nbm.1699. Epub 2011 Mar 8.
In vivo MR tracking of therapeutic microglia to a human glioma model.
Ribot EJ(1), Miraux S, Konsman JP, Bouchaud V, Pourtau L, Delville MH, Franconi
JM, Thiaudière E, Voisin PJ.
Author information:
(1)Centre de Résonance Magnétique des Systèmes Biologiques, CNRS/Université V.
Ségalen Bordeaux, 146 rue Léo Saignat, Bordeaux, France.
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.
DOI: 10.1002/nbm.1699
PMID: 21387452 [Indexed for MEDLINE]