Ultrasmall theranostic gadolinium-based nanoparticles improve high-grade rat glioma survival

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 temozolomidefor five consecutive days before radiotherapy treatment. Collectively, a series of 32 rats were divided into untreated (n = 7), temozolomide-only (n = 7), temozolomideand 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 μM. This was compared to concentrations of 10.5 ± 9.2 μM and 62.9 ± 24.7 μM 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 temozolomidewith MRT improved the median survival time (40 days) compared to the MeST of control rats (25 days) (p