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，并展示其解决神经肿瘤治疗效果诊断困境的潜力。放射治疗是恶性脑肿瘤治疗的关键方式，而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和放射性坏死，这使患者的日常护理复杂化，这是一个关键

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.