ANTIOXIDANT INHIBITION OF GLIOMAS: MRI/MRS EVALUATION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本项目重点利用活体磁共振（MR）技术、磁共振光谱（MRS）和磁共振成像（MRI）技术，在实验动物胶质瘤模型中对颅内脑肿瘤生物标志物进行体内系列检测，并评估苯叔丁基硝基酮（PBN）抑制恶性胶质瘤形成的能力。我们的假设是，PBN具有抗氧化、抗炎的特性，可以用来抑制恶性胶质瘤的形成。具体来说，我们正在使用高分辨率的体内功能性MRI和MRS方法来监测血管化和神经元代谢物的变化，作为肿瘤生物标志物，以评估PBN在预防恶性脑肿瘤形成方面的有效性。这项研究项目的成功为评估潜在化合物提供了基础，这些化合物可能作为治疗和/或预防药物，可以减少人类恶性胶质瘤的形成。我们的研究结果表明，高分辨率的体内MR血管成像提供了正常组织和肿瘤之间血管形成差异的有用信息，我们发现胶质瘤的血管生成增加。此外，功能性MRS方法可以监测神经胶质瘤中神经元代谢物的变化，如脂质的增加，Cho（胆碱）、Cr（总肌酸）和NAA （n -乙酰天冬氨酸）的减少。PBN已被发现抑制血管生成（MRA）和神经代谢物（MRS）的这些变化。研究了四种胶质瘤模型(C6, F98, 9L/lacZ和ENU（乙基亚硝基尿素）。由于出现胶质瘤的动物数量较少，因此发现ENU模型对于PBN治疗研究是不可靠的。OMRF的核磁共振设备允许尖端的体内技术用于诊断和评估潜在药物在预防恶性胶质瘤形成方面的治疗效果。这项技术最终也可以用于临床。预计所提出的基础研究和未来的临床应用将发展成为一个神经癌症MRI网络，并为俄克拉何马州神经科学中心网络做出贡献。此外，研究生目前正在参与使用生物医学成像进行肿瘤检测和治疗评估。

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.