Noninvasive Real-time Imaging of Tumors and Metastases Using Tumor-targeting Light-emitting Escherichia coli

A number of bacteria types are known to preferentially grow in tumors. We have taken advantage of this phenomenon to target luciferase-expressing Escherichia coli to tumors and metastases in mouse models to image them noninvasively. After intravenous injection of pLux-expressing E. coli (108 CFU), bioluminescence signals from the bacteria were detected exclusively in tumor tissue after 24 hours. The balanced-lethal host–vector system using the gene encoding aspartate β-semialdehyde dehydrogenase (asd) enabled stable maintenance of the pLux in the tumor-targeting E. coli. This phenomenon of selective tumor targeting and proliferation of E. coli was observed in a diverse range of tumors implanted in nude mice. More importantly, E. coli was capable of targeting both primary tumors and metastases, enabling them to be imaged noninvasively in both nude and immunocompetent mice. Our results suggest the potential clinical use of this technology for tumor targeting.