Pb-212 generator for cancer therapy

描述（由申请人提供）：本提案的长期目标是开发铅-212/铋-212 （Pb-212/bi-212）发生器和足够数量的源材料，以支持临床试验和批准的药物产品。在临床前研究中使用释放α的放射性核素正在产生有希望的结果。转移性黑色素瘤、卵巢癌和弥散性腹膜内癌的治疗方法正在研究中，并正在进行临床试验。目前还没有有效的治疗方法来治疗这些疾病，在美国，每年有超过2万人死于这些疾病。为了使这项有前景的研究继续下去，需要一种批准用于人类的同位素发生器，并需要稳定的同位素供应，以支持临床试验和批准的药物产品。

DESCRIPTION (provided by applicant): The long-term objective of this proposal is to develop a lead-212/bismuth-212 (Pb-212/bi-212) generator and sufficient amounts of source material that will support clinical trials and approved drug products. The use of alpha emitting radionuclides in pre-clinical studies is yielding promising results. Treatments for metastatic melanoma, ovarian cancer and disseminated intraperitoneal cancers are being investigated and are proceeding to clinical trials. There is no effective treatment for these diseases, which take more than 20,000 lives a year in the US. For this promising research to continue, an isotope generator that is approved for human use and a steady supply of this isotope in quantities required to support clinical trials and approved drug products is required. The current isotope generator design was developed for use in small-scale pre-clinical research and is not suited for routine use in a clinical or radiopharmaceutical environment. It is an organic resin based cation exchange column typically eluted with dilute hydrochloric acid. Organic resins are susceptible to radiolytic damage; especially from high energy/high LET alpha emissions. The acid etuate is not directly compatible with antibody or peptide labeling conditions, and it is corrosive to needles, other metallic components and septa with metallic fillers. The latter can introduce impurities that compete with the radionuclides in labeling reactions. In addition, the precursor isotopes that are used to produce this isotope generator were derived from legacy material developed during the Cold War years. This amount of this material is limited and is not sufficient to support later phase trials or approved drug products. The specific aims of this proposal is to (1) design and demonstrate a Pb-212 isotope generator that is suitable for administering to humans and for use in a clinical environment and (2) determine the optimal path to increase the amount of starting material necessary to support the production of Pb-212 generators in sufficient quantities anticipated by clinical trials and approved drug products.