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新的基于蛋白质的MRI方法，并展示其在解决神经肿瘤学治疗效果的诊断难题方面的潜力。放射治疗是治疗恶性脑肿瘤的重要手段，而放射性坏死是放射治疗的主要并发症。目前可用的核磁共振成像技术无法区分脑肿瘤治疗后的肿瘤进展和放射性坏死，这使患者的日常护理复杂化，这是一个关键问题。 这是研究脑瘤新疗法疗效的障碍。最近，我们设计了一种新的分子磁共振成像技术，称为酰胺质子转移成像(APT)，它可以检测组织中内源性可移动蛋白和多肽的酰胺质子。我们在临床前模型中的初步数据表明，与单纯放射性坏死(低信号或等信号)相比，APT成像在未经治疗的胶质瘤(相对于正常和外观正常的对侧组织而言是高信号)提供了独特的信号。这项建议的具体目标是：(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和肿瘤复发方面的准确性，以及(Ii)评估APT-MRI信号是否为预测肿瘤反应和动物生存的早期生物标志物。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记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，并预测恶性胶质瘤的放射治疗效果。这些数据是在临床人群中进行进一步研究所需要的。 公共卫生相关性：我们的目标是评估使用一种新的基于蛋白质的分子磁共振方法在临床前模型中区分放射性坏死和活动性肿瘤的能力和准确性。这一结果将建立一种新的非侵入性MRI生物标志物，用于评估存活的恶性肿瘤与放射性坏死，并预测肿瘤对治疗的反应。

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. PUBLIC HEALTH RELEVANCE: Our goal is to evaluate the ability and accuracy to distinguish between radiation necrosis and active tumor in preclinical models using a novel protein-based molecular MRI approach. The results would establish a new non-invasive MRI biomarker for assessing viable malignancy versus radiation necrosis and predicting tumor response to therapy.