Production and use of Pb-203 for cancer therapy research

描述（由申请人提供）：该项目的总体目标是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Pb-203将成为使用铅-212治疗的显像剂。在过去的五年中，研究人员在基于Pb-212靶向放疗的临床前研究中取得了可喜的结果。这些由NCI的校内和校外项目资助的许多研究的结果表明，他们希望进入临床试验阶段。目前正在开发使用Pb-212治疗转移性黑色素瘤、腹腔内弥散性卵巢癌、胰腺癌和结肠癌的疗法。这些疾病没有有效的治疗方法，据美国癌症协会估计，今年美国有超过11.2万人死于这些疾病。为了从动物研究过渡到临床试验，必须开发一种诊断性放射性核素替代治疗性Pb-212标签，以便在制备或施用相应的治疗剂量之前测量该药物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Pb-203。通过用Pb-203代替Pb-212作为放射性核素标记，Pb-212标记的治疗药物被转化为必要的生物相同的单光子显像剂。该I期SBIR将演示Pb-203的生产和标记。在I期成功完成后，将提出II期SBIR，以扩展该技术以完全支持临床试验，并最终支持批准的Pb-212标记治疗剂。

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.