Molecular MRI of Radiation Necrosis in Preclinical Models

描述（由申请人提供）：本申请的总体目标是开发基于蛋白质的新型MRI方法，并证明其解决神经肿瘤学治疗效果诊断困境的潜力。放射治疗是治疗恶性脑肿瘤的主要方法，放射性坏死是放射治疗的主要并发症。目前可用的MRI技术无法区分脑肿瘤治疗后的肿瘤进展与放射性坏死，这使得患者的日常护理变得复杂，并且是一个关键因素。 研究脑肿瘤新疗法的有效性的障碍。最近，我们设计了一种新的分子MRI技术，被称为酰胺质子转移（APT）成像，它检测组织中内源性移动的蛋白质和肽的酰胺质子。我们在临床前模型中的初步数据表明，与纯放射性坏死（低信号或等信号）相比，APT成像在未经治疗的胶质瘤中提供了独特的信号（相对于正常和正常外观的对侧组织的高信号）。该提案的具体目标是：（i）优化我们基于蛋白质的MRI技术，并确定其在区分放射性坏死与肿瘤复发方面的准确性;（ii）评估APT-MRI信号是否是预测肿瘤反应和动物存活的早期生物标志物。为了实现我们的目标，我们组建了一支由基础科学家和临床医生组成的多学科团队。这项临床前研究的结果将为一种新的成像生物标志物提供第一个准确的数据，用于识别肿瘤进展与放射性坏死，并预测恶性胶质瘤放射治疗的疗效。这些数据是需要在临床人群中进行进一步研究。

DESCRIPTION (provided by applicant): The overall goal of this application is to develop novel protein-based MRI approaches and to demonstrate their potential to resolve the diagnostic dilemma of treatment effects in neuro-oncology. Radiation therapy is a key modality for the treatment of malignant brain tumors, and radiation necrosis is a major complication of radiation therapy. The inability of currently available MRI techniques to differentiate tumor progression from radiation necrosis after brain tumor therapy complicates daily patient care, and is a critical barrier to investigating the efficacy of new therapies for brain tumors. Recently, we have designed a new molecular MRI technique, dubbed amide proton transfer (APT) imaging, which detects amide protons of endogenous mobile proteins and peptides in tissue. Our preliminary data in preclinical models demonstrate that APT imaging provides a unique signal in untreated glioma (hyperintense relative to normal and normal-appearing contralateral tissue), compared to pure radiation necrosis (hypointense or isointense). The specific aims of this proposal are: (i) Optimize our protein-based MRI techniques and determine their accuracy in distinguishing radiation necrosis from tumor recurrence and (ii) Evaluate whether APT-MRI signal is an early biomarker to predict tumor response and animal survival. To achieve our goal, we have assembled a multidisciplinary team of basic scientists and clinicians. The results of this preclinical study will provide the first accuracy data for a new imaging biomarker for identifying tumor progression versus radiation necrosis, and for the prediction the efficacy of radiation therapy in malignant gliomas. These data are needed for a further study in clinical populations.