Nanogold-Enhanced Head & Neck Cancer Radiotherapy

纳米金强化头

• 批准号: 6934699
• 负责人: James F Hainfeld
• 金额: $ 18.96万
• 依托单位: NANOPROBES, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6934699
• 关键词: computed axial tomography; disease /disorder model; epidermal growth factor; gold; head /neck neoplasm; laboratory mouse; nanomedicine; nanotechnology; nonhuman therapy evaluation; particle; pharmacokinetics; radiation therapy; squamous cell carcinoma; therapy design /development

DESCRIPTION (provided by applicant): Head and neck cancers strike 41,000 new persons each year in the U.S. Survival is only 50% and treatments leave most patients with functional deficits and disfiguration. Improved treatments are desperately needed. In preliminary studies, we achieved high levels of gold specifically in tumors after intravenous injection of Nanogold, a gold nanoparticle. Because high-Z elements absorb X-rays and increase local dose, we found irradiation of mice with tumors resulted in dramatic tumor regressions and long term survivals (86%, >lyr) compared with mice irradiated without Nanogold (20%). Here we propose to investigate Nanogold-enhanced radiotherapy in a squamous cell carcinoma murine model using tomographic and fractionated irradiation and develop targeted gold agents to find their potential to improve treatment of head and neck cancers. Nanogold will be conjugated to epidermal growth factor (EGF) since other EGF conjugates have shown excellent targeting to head and neck tumors. Pharmacokinetics will be measured using a microCT instrument to map gold biodistribution and uptake in vivo over time in the tumor and other tissues. SCCVII squamous cell carcinoma tumors will be implanted in the neck of mice and the head and neck region irradiated. End points relevant to head and neck irradiation, mucositis, salivary gland damage, and fibrosis will be evaluated. The TCD50, ED50 and Therapeutic Index with and without gold will be measured and compared to other treatments. Synchrotron generated X-rays with a mean energy of 120 keV will be used, optimal for gold enhancement. If treatments show significant promise, Philips Medical Systems, a major CT manufacturer, has indicated that they could provide CT retrofits or instruments to implement Nanogold-enhanced tomographic radiotherapy, thus making the method potentially widely available for clinical use.

描述（由申请人提供）：在美国，头颈部癌症每年袭击41，000名新患者，存活率仅为50%，治疗使大多数患者具有功能缺陷和毁容。 迫切需要改进治疗方法。 在初步研究中，我们在静脉注射纳米金（一种金纳米颗粒）后，在肿瘤中实现了高水平的金。 由于高Z元素吸收X射线并增加局部剂量，我们发现与未使用纳米金照射的小鼠（20%）相比，对患有肿瘤的小鼠进行照射导致了显著的肿瘤消退和长期存活率（86%，>lyr）。 在这里，我们建议使用断层扫描和分次照射在鳞状细胞癌小鼠模型中研究纳米金增强放射治疗，并开发靶向金制剂，以发现其改善头颈癌治疗的潜力。 纳米金将与表皮生长因子（EGF）结合，因为其他EGF结合物已显示出对头颈部肿瘤的良好靶向作用。 将使用microCT仪器测量药代动力学，以绘制肿瘤和其他组织中随时间推移的体内金生物分布和摄取。 将SCCVII鳞状细胞癌肿瘤植入小鼠颈部，并照射头部和颈部区域。 将评价与头颈部照射、粘膜炎、唾液腺损伤和纤维化相关的终点。 将测量含和不含金的TCD 50、ED 50和治疗指数，并与其他治疗进行比较。 将使用平均能量为120 keV的同步加速器产生的X射线，这是金增强的最佳选择。 如果治疗显示出重大的希望，飞利浦医疗系统，一个主要的CT制造商，已经表示，他们可以提供CT改造或仪器，以实施纳米金增强断层放射治疗，从而使该方法可能广泛用于临床使用。