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）：可以通过将放射免疫疗法（RAIT）与纳米技术结合在一起来实现新颖的癌症治疗方法。在这项指导的定量研究职业发展奖（K25）的申请中，候选人提议通过包装纳米颗粒（NPS）的放射性同位素（NPS）来提高RAIT在恶性实体瘤中的功效。该项目是候选人布莱恩·史密斯（Brian Smith）博士和导师格雷戈里·亚当斯（Gregory Adams）博士之间的独特合作，他是放射免疫疗法的尊敬的专家。中心假设是，具有免疫学靶向放射性纳米颗粒将证明对实体瘤的治疗性比偶然的偶联物更有效。该假设将使用rhenium radiotal进行测试，rhenium radiotal具有两个用于RAIT的同位素，以及针对肿瘤相关的HER2/NEU抗原的单链FV（SCFV）抗体。提出了三组实验。第一组（AIM 1）着重于水溶性rhenium nps的合成。第二组（AIM 2）涉及SCFV分子与NP的附着，以及定量这些纳米颗粒放射免疫偶联物（NPRICS）的体外性能。结果将指导综合参数的更改，以便生成具有有希望的体内应用属性的NPRIC。在第三组（AIM 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NPR的生物分布和治疗功效。 该项目的执行将为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，以从事跨学科职业，以应用纳米技术在癌症检测和治疗中。特定的职业目标是（a）在核医学，免疫学和癌症生理学领域的教育，（b）生物医学实验室实践培训，包括免疫化学和放射化学，以及（c）在适当进行动物研究中进行培训。