Ultrasmall theranostic gadolinium-based nanoparticles improve high-grade rat glioma survival.
J Clin Neurosci
; 67: 215-219, 2019 Sep.
Article
em En
| MEDLINE
| ID: mdl-31281087
ABSTRACT
We formulated an ultra-small, gadolinium-based nanoparticle (AGuIX) with theranostic properties to simultaneously enhance MRI tumor delineation and radiosensitization in a glioma model. The 9L glioma cells were orthotopically implanted in 10-week-old Fischer rats. The intra-tumoral accumulation of AGuIX was quantified using MRI T1-maps. Rats randomized to intervention cohorts were subsequently treated with daily temozolomide for five consecutive days before radiotherapy treatment. Collectively, a series of 32 rats were divided into untreated (nâ¯=â¯7), temozolomide-only (nâ¯=â¯7), temozolomide and MRT (nâ¯=â¯9), AGuIX and MRT (nâ¯=â¯7), and triple therapy (temozolomide, AGuIX NPs, and MRT; nâ¯=â¯9) cohorts. AGuIX nanoparticles achieved a maximum intra-tumoral concentration (expressed as concentration of Gd3+) at 1â¯h after intravenous injection, reaching a mean of 227.9⯱â¯60⯵M. This was compared to concentrations of 10.5⯱â¯9.2⯵M and 62.9⯱â¯24.7⯵M in the contralateral hemisphere and cheek, respectively. There was a slower washout in the intra-tumor region, with sustained tumor-to-contralateral ratio of AGuIX, up to 14-fold, for each time point. The combination of AGuIX or temozolomide with MRT improved the median survival time (40â¯days) compared to the MeST of control rats (25â¯days) (pâ¯<â¯0.002). There was a trend towards further increased survival when the three treatments were combined (MeST of 46â¯days). This study demonstrated the selective accumulation of AGuIX in high grade glioma, as well as the potential survival benefits when combined with chemoradiation.
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Assunto principal:
Radiossensibilizantes
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Neoplasias Encefálicas
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Nanomedicina Teranóstica
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Gadolínio
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Glioma
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article