Imaging and Tissue Biomarkers in the Treatment of Brain Tumors

描述（由申请人提供）：总体目标是将生理神经成像和组织生物标志物的技术发展进展整合到脑肿瘤患者的管理中，并将这些知识转化为优化治疗。恶性胶质瘤是一个重大的临床挑战，在开发新的治疗策略方面花费了大量的努力。虽然放射治疗（XRT）延长了多形性胶质母细胞瘤（GBM）的生存，但大约30%的患者在XRT治疗过程中病情进展，预后较差。项目1将研究代谢、生理成像和组织相关的潜力，以便在治疗开始前识别这些患者，并将这些知识整合到个性化治疗范例中。GBM患者普遍进展，这些复发肿瘤在其行为上是异质的。除了患者相关的预后因素（年龄和运动状态）外，没有生物学预测预后的因素。项目2将研究与组织相关的非侵入性生理代谢参数，以更好地了解肿瘤的异质性和生物学行为。这些信息应该对临床试验患者的选择以及结果的设计和解释产生重大影响。如果生理成像参数确实代表了生物行为，如血管生成或侵入能力，这将在评估新的靶向治疗中有重要的应用。新的治疗方法包括向肿瘤浸润的脑实质输送药物。浸润性肿瘤浸润成分的范围和性质在标准影像学上是有限的。项目3将研究药物在动物和非人类灵长类动物间质给药的无创实时成像，以确定输注靶点并优化治疗药物的递送。临床服务核心和成像与组织相关核心将为所有项目提供服务，以集中有效和综合管理该计划项目拨款。

DESCRIPTION (provided by applicant): The overall goal is to integrate advances in technological development of physiologic neuro-imaging and tissue biomarkers in the management of patients with brain tumors and to translate this knowledge to optimize treatment. Malignant glioma is a significant clinical challenge and much effort is expended in the development of new therapeutic strategies. Although radiation therapy (XRT) prolongs survival for glioblastoma multiforme (GBM), about 30 percent of patients progress during the course of XRT and have a poor prognosis. Project 1 will study the potential of metabolic and physiologic imaging and tissue correlates to identify these patients prior to initiation of therapy and to integrate this knowledge in an individualized treatment paradigm. Patients with GBM universally progress and these recurrent tumors are heterogeneous in their behavior. Apart from patient-related prognostic factors (age and performance status), there are no biological predictors of outcome. Project 2 will study the non-invasive physiologic and metabolic parameters with tissue correlates to better understand tumor heterogeneity and biological behavior. This information should have a major impact on the selection of patients for clinical trials and the design and interpretation of results. If the physiologic imaging parameters are indeed representative of biological behavior such as angiogenesis or invasive capacity, this will have significant application in the evaluation of novel targeted therapies. New therapeutic approaches involve the interstitial delivery of agents into tumor-infiltrated brain parenchyma. Determining the extent and nature of the invasive component of infiltrative tumor is limited with standard imaging. Project 3 will study the non-invasive real-time imaging of interstitial administration of agents in animals and non-human primates to define the target for infusion and optimize delivery of therapeutic agents. The Clinical Services Core and Imaging and Tissue Correlate Core will provide services to all projects to centralize the effort for efficient and integrated management of this program project grant.