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.
