SBIR-STTR Award

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.

Thesaurus Terms:
lead, radionuclide, radionuclide imaging /scanning, radiotracer, technology /technique development chemical conjugate, evaluation /testing, particle accelerator, peptide, physical separation, thallium affinity labeling, bioimaging /biomedical imaging

Promising results are being obtained from studies of molecules labeled with Lead-212 (Pb-212) as potential targeted radiotherapeutic agent against metastatic melanoma. According to the American Cancer Society approximately 60,000 people in the US will be diagnosed with melanoma this year, and 8,000 will die from this disease. For Pb-212 melanoma therapy to proceed to clinical trials, it requires an imaging surrogate for treatment planning and disease staging. The Federal Food and Drug Administration recommended Pb-203 be developed as the imaging companion, the subject of this application. To prepare for clinical trials, animal studies will demonstrate that Pb-203 imaging isotope is a viable substitute for the therapeutic Pb-212 label. Animal studies will be performed to determine the agent's affinity for tumor cells, biodistribution will be assessed. Additionally to satisfy FDA requirements for clinical trials and approved drug product, a Pb-203 production method will be developed so that the isotope can be produced to support Pb-212 based therapies. After successful completion of this Phase II SBIR, AlphaMed will have completed the preclinical animal work needed to support an IND application for using Pb-203 labeled [DOTA]-ReCCMSH as the imaging partner for its Pb-212 based melanoma therapy. To support other Pb-212 based therapies, AlphaMed will have its Pb-203 production method listed as a Drug Master File, available to be referenced in IND applications. Targeted radiotherapy has shown to be very effective in preclinical tests in treating metastatic melanoma, a deadly form of skin cancer that takes 8,000 lives a year in the US. To proceed to clinical trials, an imaging isotope of the same element as the therapeutic will be used for treatment planning. Successful completion of this grant application will demonstrate the proposed imaging isotope is suitable and an acceptable isotope production process is established.

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Thesaurus Terms:
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