Imaging and Tissue Biomarkers in the Treatment of Brain Tumors

描述(由申请人提供)：总体目标是将生理学神经成像和组织生物标记物技术发展的进步整合到脑瘤患者的治疗中，并将这一知识转化为优化治疗。恶性胶质瘤是一个重大的临床挑战，在新的治疗策略的开发上花费了大量的精力。尽管放射治疗(XRT)延长了多形性胶质母细胞瘤(GBM)的生存时间，但约30%的患者在XRT过程中进展，预后较差。项目1将研究代谢、生理成像和组织相关性的潜力，以便在开始治疗之前识别这些患者，并将这些知识整合到个性化治疗范例中。GBM患者普遍进展，这些复发的肿瘤在行为上是异质性的。除了与患者相关的预后因素(年龄和表现状态)外，没有生物学上的预后预测因素。项目2将研究与组织相关的非侵入性生理和代谢参数，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能代表血管生成或侵袭能力等生物学行为，这将在评估新的靶向治疗方面具有重要的应用价值。新的治疗方法包括通过间质给药进入肿瘤浸润性脑实质。用标准成像来确定浸润性肿瘤的侵袭成分的范围和性质是有限的。项目3将研究动物和非人类灵长类动物体内药物间质给药的非侵入性实时成像，以确定输液目标并优化治疗剂的输送。临床服务核心以及成像和组织相关核心将为所有项目提供服务，以集中力量对该计划项目赠款进行有效和综合的管理。

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.