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

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 ± 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. J. Magn. Reson. Imaging 2010;31:796–806. ©2010 Wiley‐Liss, Inc.