Multiparametric assessment of the anti-glioma properties of OKN007 by magnetic resonance imaging

Abstract

Purpose: To demonstrate that OKN007, a disulfonyl derivative of phenyl-tert-butyl nitrone (PBN), has anti-glioma activity in the clinically relevant C6 rat glioma model using multi-parametric magnetic resonance imaging. Materials and Methods: Twenty-one rats were intracerebrally implanted with C6 cells and administered OKN007 or kept as controls. Animals were monitored with MRI at 7 Tesla (T), using morphologic, diffusion-weighted and perfusion imaging, followed by histology and Western blots of angiogenesis and inflammatory markers. Results: OKN007 was found to decrease tumor volumes and increase survival. The glioma tissues of OKN007-treated rats were found to have longitudinal apparent diffusion coefficients (ADC z) of 0.76 ± 0.06 × 10 -3 mm 2 /s, similar to the contralateral tissue and significantly smaller than untreated gliomas (0.97 ± 0.13 × 10 -3 mm 2 /s). They had higher perfusion rates (66 6 4 mL/100 g·min) than untreated gliomas (26 ± 7 mL/100 g·min). All examined molecular markers were decreased in OKN007-treated rat gliomas, compared with elevated levels in untreated rats. Conclusion: MRI assessment was successfully used to monitor a decrease in tumor growth, and corresponding alterations in ADC and perfusion rates in rat C6 gliomas treated with the anti-glioma agent, OKN007. © 2010 Wiley-Liss, Inc.