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 (n?=?7), temozolomide-only (n?=?7), temozolomide and MRT (n?=?9), AGuIX and MRT (n?=?7), and triple therapy (temozolomide, AGuIX NPs, and MRT; n?=?9) cohorts. AGuIX nanoparticles achieved a maximum intra-tumoral concentration (expressed as concentration of Gd3+) at 1?h after intravenous injection, reaching a mean of 227.9?±?60?muM. This was compared to concentrations of 10.5?±?9.2?muM and 62.9?±?24.7?muM 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 (40?days) compared to the MeST of control rats (25?days) (p?

View details for DOI 10.1016/j.jocn.2019.05.065

View details for PubMedID 31281087