Effects of PBN and OKN007 in rodent glioma models assessed by 1H MR spectroscopy |
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Authors: | He Ting Doblas Sabrina Saunders Debra Casteel Rebba Lerner Megan Ritchey Jerry W Snider Tim Floyd Robert A Towner Rheal A |
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Affiliation: | a Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USAb Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAc Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USAd Experimental Therapeutics Research Laboratory, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA |
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Abstract: | Gliomas, the most common primary brain tumors in adults, have a poor outcome. PBN (α-phenyl-tert-butylnitrone) and OKN007 (2,4-disulfophenyl-PBN) are nitrones that have demonstrated beneficial effects in many aging diseases. In this study, we evaluated the anti-tumor effects of PBN and OKN007 in several rodent glioma models (C6, RG2, and GL261) by assessing metabolite alterations with magnetic resonance spectroscopy (MRS). PBN or OKN007 was administered in drinking water before or after tumor formation. MR imaging and single-voxel point-resolved spectroscopy were done to assess tumor morphology and metabolites, after therapy. Major metabolite ratios (choline, N-acetylaspartate, and lipid (methylene or methyl), all compared to creatine), as well as quantification of individual metabolite concentrations, were assessed. Nitrones induced tumor metabolism changes that resulted in restoring major metabolite ratios close to their normal levels, in the glioma regression phase. Nitrone treatment decreased the lipid (methylene)-to-creatine ratio, as well as the estimated concentration of lipid (methylene) significantly. Alterations in lipids can be a useful marker for the evaluation of the efficacy associated with treatment and were found in this study to be related to the reduction of necrosis, but not apoptosis. OKN007 was more effective than PBN when administered after tumor formation in the C6 glioma model. In conclusion, 1H MRS and conventional MRI are useful methods to assess and follow the response of varied glioma models to anti-tumor treatments. |
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Keywords: | Cho, choline Cr, creatine GBM, glioblastoma multiforme HR-MAS, high-resolution magic angle spinning Lip, lipid MRI, magnetic resonance imaging MRS, magnetic resonance spectroscopy NAA, N-acetylaspartate PBN, α-phenyl-tert-butylnitrone PCr, phosphocreatine PRESS, point-resolved spectroscopy TE, echo time TR, repetition time VEGF, vascular endothelial growth factor |
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