Nanoparticle-Directed Photothermal Ablation of Primary Brain Tumors guided by Mag

描述（由申请人提供）：美国脑肿瘤的发病率，包括原发性和其他癌症的转移，估计每年约为20万例。目前的治疗方法包括开放手术、放疗和化疗，但这些治疗方法对大多数患者都不能治愈，而且对一些患者会产生严重的副作用。迫切需要一种治疗方法，既能改善治疗结果，副作用又比目前的治疗方法少，同时又能与目前的治疗方法协同作用。我们之前已经完成了一项微创、纳米颗粒定向、图像引导治疗犬脑肿瘤模型实体瘤光热消融的可行性研究。这项研究计划将把这些初步研究转化为临床应用，并在项目结束时为人体临床试验提供基础。使用犬胶质瘤细胞系，我们将证明系统传递，红外吸收纳米粒子将自行选择肿瘤边界。利用磁共振温度成像，我们将证明光热消融可以局限于肿瘤特异性治疗区域，导致清晰的边缘，对邻近神经组织的损害最小。该疗法的选择性将通过急性（48-72小时）病理和更长时间（6周）的生存研究来评估。经皮光热治疗的微创性可以减少肿瘤体积和降低颅内压，从而提高患者的生活质量，从而减少癫痫发作和头痛的发生率。而且，降低癌症患者的发病率将允许其他治疗，如化疗，这与光热疗法不冲突。此外，微创，经皮传递光热疗法可能允许治疗不可切除的深层或颅骨肿瘤。

DESCRIPTION (provided by applicant): The incidence of brain tumors in the U.S., including primary and metastases of other cancers, is estimated to be around 200,000 per year. Current treatments consist of open surgery, radiation, and chemotherapy, but these treatments are by no means curative for most patients and result in substantial side effects for some patients. There is a significant need for therapies that improve outcomes with fewer side effects than current therapies, but which are also synergistic with current approaches. We have previously completed a feasibility study of a minimally invasive, nanoparticle-directed, image- guided therapy for the photothermal ablation of solid tumors in a canine brain tumor model. This proposed research project will translate these preliminary studies into a clinical application and provide the basis for a human clinical trial at the conclusion of the project. Using a canine glioma cell line, we will demonstrate that systemically-delivered, infrared absorbing nanoparticles will self-select for the tumor boundary. Using Magnetic Resonance temperature imaging, we will demonstrate that the photothermal ablation can be confined to a tumor-specific treatment zone, resulting in clear margins with minimal damage to adjacent neural tissue. The selectivity of this therapy will be assessed by acute (48-72 hour) pathology and longer (6 week) survival studies. The minimally-invasive nature of the percutaneous photothermal treatment should lead to an enhancement of patients' quality of life as a result of reduced tumor volume and reduced intracranial pressure, which should reduce the incidence of seizures and headaches. And, a lowered morbidity in cancer patients would permit other treatments such as chemotherapy which do not conflict with this photothermal therapy. Additionally, a minimally invasive, percutaneously delivered photothermal therapy may permit treatment of non-resectable deeper or skull-based tumors. PUBLIC HEALTH RELEVANCE: The incidence of brain tumors in the U.S., including primary and metastases of other cancers, is approximately 200,000 per year. The currently accepted treatment modalities for tumors of the brain include surgery, whole-brain radiotherapy, stereotactic radiosurgery, chemotherapy; or some combination of these, but these treatments are by no means curative for most patients and result in substantial side effects for some patients. We will develop a minimally invasive therapy to eliminate or reduce in size primary tumors in the brain and skull, improving outcomes and reducing morbidity.