Lack of prognostic tools to access the proliferative status of breast cancer has been one of the major hurdles in breast cancer treatment planning patient management. Current approaches (tumor biopsy and fine needle aspirates) in the measurement of the metastatic potential of breast cancer suffer from a low predictability (10-35 percent) due to variability of tissue sampling. The goal of the proposed research is to develop Single Photon Emission Computed Tomography (SPECT) based radiopharmaceuticals that can provide a non-invasive means of assessing the proliferative status of breast tumors in vivo and avoid the issues related to improper tissue sampling. Sigma-2 receptors have emerged as a biomarker for breast cancer since they are found over expressed in solid breast tumors and the density of sigma-2 receptors is proportional to the proliferative status of breast tumor cells both in vitro and in vivo. Therefore, a sigma-2 receptor ligand carrying a radionuclide such as technetium-99m may provide the means to detect breast cancer and its proliferative status by applying imaging techniques such as Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET). We have identified a group of small organic compounds that possess a high binding affinity and high selectivity for sigma-2 receptors. In the Phase I SBIR project we plan to apply newly improved synthetic routes to incorporate technetium-99m/rhenium complexes into these highly selective sigma-2 ligands, which are ideal for Single Photon Emission Computed Tomography. These compounds will be evaluated for binding to sigma receptors using in vitro binding assays.
Commercial Applications and Other Benefits as described by the awardee: The product developed in this Phase I SBIR project is a tumor-targeting non-invasive imaging technique that will benefit breast cancer patients in treatment strategy planning and long-term disease control by providing vital information regarding the proliferative status of the tumor. It can also be used as a breast cancer screening technique, which will greatly improve the efficiency and accuracy of the tumor detection. The technique developed in this Phase I SBIR project can also be translated into other area of cancer diagnosis and patient management such as lung cancer, glioblastoma, melanoma, head and neck cancers. The product processes a strong commercial potential because of the widespread availability and low-cost of technetium-99m generators and scanners throughout the country.
