Cancer Therapy with Targeted Radioactive Nanoparticles

靶向放射性纳米颗粒的癌症治疗

• 批准号: 7074607
• 负责人: Brian Smith
• 金额: $ 12.27万
• 依托单位: FOX CHASE CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-09 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7074607
• 关键词: adenomatous polyps; antibody; antineoplastics; athymic mouse; autoradiography; dosage forms; drug delivery systems; drug design /synthesis /production; drug screening /evaluation; electron microscopy; flow cytometry; genetically modified animals; immunoconjugates; light scattering; nanomedicine; nanotechnology; neoplasm /cancer radioimmunotherapy; nonhuman therapy evaluation; pharmacokinetics; radiation dosage; radionuclides; small molecule

DESCRIPTION (provided by applicant): Novel cancer treatments could be realized by marrying radioimmunotherapy (RAIT) with nanotechnology. In this application for a Mentored Quantitative Research Career Development Award (K25), the Candidate proposes to increase the efficacy of RAIT in the setting of malignant solid tumors by packaging radioisotopes in the form of nanoparticles (NPs). This project is a unique collaboration between Candidate Dr. Brian Smith and Mentor Dr. Gregory Adams, who is a respected expert in radioimmunotherapy. The central hypothesis is that immunologically targeted radioactive nanoparticles will prove more therapeutically effective against solid tumors than is typical for RAIT conjugates. This hypothesis will be tested using rhenium radiometal, which has two useful isotopes for RAIT, and single chain Fv (scFv) antibodies which target the tumor-associated HER2/neu antigen. Three sets of experiments are proposed. The first set (Aim 1) focuses on the synthesis of water soluble rhenium NPs. The second set (Aim 2) relates to attachment of scFv molecules to the NPs, and to quantification of the in vitro performance of these nanoparticle radioimmunoconjugates (NPRICs). The results will guide changes to the synthesis parameters in order to produce NPRICs with promising properties for in vivo application. In the third set (Aim 3), the biodistribution and treatment efficacy of optimized NPRICs will be studied in immunodeficient mice with tumor xenografts. Execution of this project will provide Dr. Smith, who is trained as a materials scientist, with the necessary knowledge and skills to pursue a cross-disciplinary career in the application of nanotechnology to cancer detection and treatment. Specific career goals are (a) education in the areas of nuclear medicine, immunology, and cancer physiology, (b) training in biomedical laboratory practices including immunochemistry and radiochemistry, and (c) training in the proper conduct of animal studies.

描述（由申请人提供）：通过将放射免疫疗法（RAIT）与纳米技术相结合，可以实现新型癌症治疗。在本次指导定量研究职业发展奖 (K25) 申请中，候选人提出通过以纳米颗粒 (NP) 形式包装放射性同位素来提高 RAIT 在治疗恶性实体瘤中的功效。该项目是候选人 Brian Smith 博士和导师 Gregory Adams 博士（放射免疫治疗领域受人尊敬的专家）之间的独特合作。中心假设是，免疫学靶向的放射性纳米颗粒将证明比典型的 RAIT 缀合物对实体瘤更有效。这一假设将使用铼放射性金属（其具有两种对 RAIT 有用的同位素）和针对肿瘤相关 HER2/neu 抗原的单链 Fv (scFv) 抗体进行测试。提出了三组实验。第一组（目标 1）重点关注水溶性铼纳米颗粒的合成。第二组（目标 2）涉及 scFv 分子与 NP 的附着，以及这些纳米颗粒放射免疫缀合物 (NPRIC) 体外性能的量化。结果将指导合成参数的改变，以生产具有在体内应用前景良好的特性的 NPRIC。在第三组（目标 3）中，将在具有肿瘤异种移植物的免疫缺陷小鼠中研究优化的 NPRIC 的生物分布和治疗效果。 该项目的执行将为接受过材料科学家培训的史密斯博士提供必要的知识和技能，以从事纳米技术应用于癌症检测和治疗的跨学科职业。具体的职业目标是（a）核医学、免疫学和癌症生理学领域的教育，（b）包括免疫化学和放射化学在内的生物医学实验室实践培训，以及（c）正确进行动物研究的培训。