Molecular Cages for Alpha Particle Radioimmunotherapy

放射免疫疗法（RIT）是一种很有前途的癌症治疗方法，其中放射性核素与仅在肿瘤细胞上表达的抗原特异性单克隆抗体相关联。一旦mAb定位到肿瘤细胞，放射性核素就会衰变并杀死细胞。到目前为止，经过临床试验的化合物都是基于释放β的放射性核素，因为它们可以可靠地与单抗联系起来。然而，α辐射对分布癌具有显著的优势，包括短路径长度和更大的细胞毒性。由于缺乏治疗上理想半衰期的放射性核素的强大螯合剂，α辐射核素的发展受到严重阻碍。该项目旨在开发一种100%安全壳的新封装，适用于所有锕系放射性核素。拟议的商业应用：这种封装将使α粒子RIT方法能够用于治疗白血病、淋巴瘤、微转移、肺癌和其他肿瘤小于几个细胞直径的癌症。这种疗法的发展有大约30万美国人/年的潜在市场。

Radioimmunotherapy (RIT) is a promising therapy for cancer, wherein radionuclides are linked to monoclonal antibodies specific for antigens expressed solely on tumor cells. Once the mAb locates the tumor cell, the radionuclide decays and kills the cell. The compounds that have so far undergone clinical trials are based on beta-emitting radionuclides, because they can be reliably linked to the mAb. However, alpha radiation has significant advantages for distributed carcinomas, including short path length and much greater cytotoxicity The development of alpha-emitting radionuclides has been severely hampered by a lack of robust chelates for radionuclides with therapeutically desirable half- lives. This project aims to develop a new encapsulate with 100% containment, suitable for all actinide radionuclides. PROPOSED COMMERCIAL APPLICATIONS: This encapsulate will enable alpha particle RIT methods to be developed for the treatment of leukemias, lymphomas, micrometastates, lung cancer, and other cancers where tumors are smaller than a few cell diameters. The development of such a therapy has a potential market of approximately 300,000 Americans/yr.