Cancer Detection Cancer is a complex disease that develops due to genetic alterations in oncogenes and tumor suppressor genes and abnormalities in gene expression that provide growth advantage and metastatic potential to the cells. An important example is prostate cancer. It was estimated that, in the year 2005, there were more than 230,000 new cases and about 30,000 deaths of prostate cancer patients in the United States alone. Approximately one in seven American men will be diagnosed with prostate cancer during their lifetime, making it the most commonly diagnosed solid tissue cancer in the United States. Despite advances in prevention and early detection, refinements in surgical technique, and improvements in adjuvant radio- and chemotherapy, the ability to cure many patients with prostate cancer remains elusive. While some localized lesions are amenable to cure with surgery or radiation, metastatic disease continues to be a major source of morbidity and mortality, and the ability to choose the best treatment is limited. Therefore, there is an urgent need to develop new molecular imaging methods based on genetic alterations and antigenic changes in a cell so that better diagnosis, prognosis and treatment of cancer can be realized. We have been developing molecular beacon based methods, aiming to detect tumor-marker genes in cells and tissue specimens with high specificity and sensitivity, allowing a better understanding of tumor biology, and leading to better cancer diagnosis and therapy. The goal of the cancer research projects in the Bao Lab is to establish the ability of in vivo detection of tumor-marker genes with increased sensitivity and specificity using optical imaging, thus providing tools for early detection of cancer, and for clinical evaluation of cancer prognosis and treatment strategies. The specific research topics include: (1) determine the signal-to-background ratio, specificity and sensitivity of molecular beacon based methods in detecting gene expression levels in living cells; (2) enhancing the intracellular stability of molecular beacons by modifying the backbone chemistry; (3) establishing the ability of molecular beacons to quantify relative changes of mRNA expression of multiple cancer markers; (4) demonstrating the capability of molecular beacons in detecting single-base mutations of tumor marker genes; (5) developing NIR molecular beacons for in vivo imaging and demonstrate tissue delivery capabilities, and (6) studying the interaction between cancer-marker mRNA and RNA-binding proteins. We will also develop new activatable nanoprobes such as quantum-dot and lanthanide chelate based linear or hairpin probes for high-sensitivity tumor marker detection in living cells.