Production and use of Pb-203 for cancer therapy research

描述(申请人提供)：该项目的总体目标是在常规基础上以合理的价格生产大量高质量的铅-203，以支持癌症研究和批准的药物产品。预计铅-203将成为使用铅-212进行治疗的显像剂。在过去的五年里，研究人员在基于铅-212靶向放射治疗的临床前研究中取得了令人振奋的结果。这些研究中的许多都是由NCI的校内和校外项目资助的，因此他们预计将进入临床试验。使用铅-212的治疗方法正在开发中，用于治疗转移性黑色素瘤以及腹膜内播散性卵巢癌、胰腺癌和结肠癌。据美国癌症协会估计，这些疾病今年在美国夺走了超过11.2万人的生命，目前还没有有效的治疗方法。为了从动物实验过渡到临床试验，有必要开发一种诊断放射性核素替代治疗性的铅-212标记，以便在准备或给予相应的治疗剂量之前可以测量该试剂对肿瘤细胞的亲和力和生物分布。幸运的是，根据生物医学成像机构间委员会的建议，有一种合适的放射性核素，即铅-203。通过用铅-203代替铅-212作为放射性核素标记，铅-212标记的治疗性药物被转化为所需的生物相同的单光子显像剂。第一阶段SBIR将演示铅-203的生产和标签。在第一阶段成功完成后，将提出第二阶段SBIR，以扩展该技术，以完全支持临床试验，并最终支持经批准的铅-212标签治疗剂。

DESCRIPTION (provided by applicant): The overall goal of this project is to produce large amounts of high-quality lead-203 on a routine basis, at reasonable prices to support cancer research and approved drug products. It is expected that Pb-203 will be the imaging agent for therapies using lead-212. Over the last five years researchers have been obtaining promising results in pre-clinical studies based on targeted radiotherapy using Pb-212. The results of many of these studies, which are being funded by NCI's intramural and extramural programs, are such that they expect to proceed to clinical trials. Therapies using Pb-212 are being developed for metastatic melanoma, and intraperitoneal disseminated ovarian, pancreatic and colon cancers. There is no effective treatment for these diseases, which are estimated by the American Cancer Society to take more than 112,000 lives this year in the US. In order to transition from animal studies into clinical trials it is essential to develop a diagnostic radionuclide substitute for the therapeutic Pb-212 label so that the agent's affinity for tumor cells and biodistribution can be gauged before the corresponding therapeutic dose is prepared or administered. Fortunately, as recommended by the Interagency Council on Biomedical Imaging, there is a suitable radionuclide, Pb-203. By substituting Pb-203 for Pb-212, as the radionuclide label, a Pb-212 labeled therapeutic is converted into the requisite biologically identical single photon-imaging agent. This Phase I SBIR will demonstrate the production and labeling of Pb-203. After successful completion of Phase I, a Phase II SBIR will be proposed to expand the technology to fully support clinical trials, and ultimately support approved Pb-212 labeled therapeutic agents.