Magnetic resonance imaging approaches to follow-up the outcome of a glioblastoma rat model with anti-inflammatory -NSAIDs and SAIDS- treatments

Trabajo presentado en el 37th Annual Meeting; European Society for Magnetic Resonance In Medicine and Biology (ESMRMB), celebrado en Rotterdam (Países Bajos) del 3 al 5 de octubre de 2019.[Purpose/Introduction]: Glioblastoma (GBM) is the most aggressive human brain tumor, with poor prognosis and survival. Agents with anti-inflammatory (AI) properties have been studied as anti-tumoral drugs2 and tested in GBM models with promising results. We have worked with GBM murine models, identifying MRI parameters to be used as biomarkers of the pathology. In this work we aimed to assess the overall survival (OS) and the tumor features evolution of GBMbearing rats treated with either non-steroidal AI (NSAID) or steroidal AI drugs (SAID).[Subjects and Methods]: GBM was induced in Wistar rats by stereotaxic injection of C6 cells4. When tumors were visible by MRI, animals were randomized in 3 groups: 5 rats were injected s.c. (3 days) with a NSAID (meloxicam, 1 mg/kg), 5 rats with a SAID (methylprednisolone, 1 mg/kg) and 3 with saline (controls). MRI evaluations were carried out in a 7T system until day 45 postcell injection (or until end-point criteria). Tumor volume was followed-up with Gd contrast-enhanced T1 W images at different times after C6 injection. Besides, diffusion-weighted and magnetization transfer (MT) images were acquired before and 1 week after starting the treatment. Parametric maps were generated with home-made software. Therapy success was evaluated by calculating the relative tumor volume at the end of the study (RTVf) compared with the pre-therapy size and the OS of the different groups.[Results]: Higher OS was observed in animals treated with AI drugs (32.2 ± 12.6 days for rats treated with NSAID and 28.2 ± 10.0 for rats treated with SAID), than control rats (20.0 ± 2.0 days). RTVf reached higher volume in the control group than in the treated groups with NSAID and SAID. Moreover, the glioma volume of 2 rats treated with meloxicam and 1 rat with methylprednisolone progressively decreased until a complete regression. Fig. 1 shows three examples of tumor evolution of a control rat and 2 treated that showed a total regression, and Fig. 2 the T1 W images of these animals.Mean diffusivity (MD) and MT maps of control and treated rats -1 week after starting the treatment- are shown in Fig. 3. MD values were higher in the tumor area of the rat treated with SAID compared with treated with NSAID and control, while MT values were lower.[Discussion/Conclusion]: These preliminary results point meloxicam (NSAID) and methylprednisolone (SAID) as potential candidate therapies against GBM. Differences in the studied MRI parameters (MD and MT) indicate that the distinct AI effect is translated in a different behavior of the functional MRI biomarkers. This can potentially give useful information about the therapy effect and improve the therapy follow-up