Real-Time Imaging of Tumors Using Replication-Competent Light-Emitting Microorganisms

Early detection of cancer and metastases is pivotal to the success of subsequent treatment intervention. In recent years, the use of live microorganisms, such as viruses and bacteria, has gained substantial research and clinical interest in both detection and therapy of cancer. Many of these live microorganisms have shown remarkable tumor-specific replication following systemic delivery. With the aid of modern molecular technologies, modified live microorganisms can be engineered to carry additional diagnostic and therapeutic capabilities. We have shown that when armed with light-emitting protein genes, such as genes for luciferase and green fluorescent protein, the entry and specific amplification of systemically-delivered vaccinia virus and bacteria in tumors can be visualized in real time using a low-light imager, or using macro- and micro-fluorescence microscopes. Therefore, through optical imaging, the location of tumors and metastases could be revealed by these light-emitting microorganisms. The tumor-colonization capability has been demonstrated in both immuno-competent as well as immuno-compromised rodent models with syngeneic and allogeneic tumors. Based on their “tumor-finding” nature, bacteria and viruses could be further designed as “vehicles” to carry multiple genes for detection and therapy of cancer.