ANTIOXIDANT INHIBITION OF GLIOMAS: MRI/MRS EVALUATION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project is focused on the use of in vivo magnetic resonance (MR) techniques, magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) for the serial in vivo detection of intracranial brain tumor biomarkers in experimental animal glioma models, and the assessment of phenyl tert-butyl nitrone (PBN) in its ability to suppress malignant glioma formation. Our hypothesis is that PBN, which has antioxidant, anti-inflammatory properties, can be used to inhibit the formation of malignant gliomas. Specifically, we are using high resolution in vivo functional MRI and MRS methods to monitor changes in vascularization and neuronal metabolites, as tumor biomarkers, to evaluate the effectiveness of PBN in preventing malignant brain tumor formation. The success of this research project serves as the basis for the evaluation of potential compounds that may be useful as therapeutic and/or prophylaxis agents that can reduce the formation of malignant gliomas in humans. Our results show that high resolution in vivo MR angiography provides useful information on vascularization differences between normal tissues and tumors, and we have found that gliomas have increased angiogenesis. Also functional MRS methods can monitor changes in neuronal metabolites in gliomas, such as an increase in lipids, and decreases in Cho (choline), Cr (total creatine), and NAA (N-acetyl aspartate). PBN has been found to inhibit these changes in angiogenesis (MRA) and in neural metabolites (MRS). Four glioma models have been investigated (C6, F98, 9L/lacZ and ENU (ethyl nitroso urea). The ENU model was found to be unreliable for PBN treatment studies due to the low number of animals presenting gliomas. The MRI Facility at OMRF allows cutting edge in vivo technology to be used for both the diagnosis as well as the assessment of the therapeutic effectiveness of potential agents in preventing malignant glioma formation. The technology can also eventually be adapted for clinical use. It is anticipated that the proposed basic research, and future clinical applications will develop into a neurological cancer MRI network in and contribute to the Oklahoma Center for Neuroscience network. In addition, graduate students are currently participating in the use of biomedical imaging for tumor detection and therapy evaluation.