OKN-007 decreases tumor necrosis and tumor cell proliferation and increases apoptosis in a preclinical F98 rat glioma model

Background Glioblastoma is a malignant World Health Organization (WHO) grade IV glioma with a poor prognosis in humans. New therapeutics are desperately required. The nitrone OKN‐007 (2,4‐disulfophenyl‐PBN) has demonstrated effective anti‐glioma properties in several rodent models and is currently being used as a clinical investigational drug for recurrent gliomas. We assessed the regional effects of OKN‐007 in the tumor necrotic core and non‐necrotic tumor parenchyma. Methods An F98 rat glioma model was evaluated using proton magnetic resonance spectroscopy (1H‐MRS), diffusion‐weighted imaging (DWI), morphological T2‐weighted imaging (T2W) at 7 Tesla (30 cm‐bore MRI), as well as immunohistochemistry and microarray assessments, at maximum tumor volumes (15–23 days following cell implantation in untreated (UT) tumors, and 18–35 days in OKN‐007‐treated tumors). Results 1H‐MRS data indicates that Lip0.9/Cho, Lip0.9/Cr, Lip1.3/Cho, and Lip1.3/Cr ratios are significantly decreased (all P