Telomerase-specific fluorescent navigation system for lung cancer surgery

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Currently available methods for detection of tumors in vivo such as X-ray, computed tomography, and ultrasonography are noninvasive and well studied; the images, however, are not specific for tumors. Direct optical imaging of tumor cells in vivo that can clearly distinguish them from surrounding normal tissues may be clinically useful. Here, we describe a new approach to visualizing tumors whose fluorescence can be detected using telomerase-specific replication-competent adenovirus expressing green fluorescent protein (GFP) (OBP-401). OBP-401 contains the replication cassette, in which the human telomerase reverse transcriptase (hTERT) promoter drives expression of El genes, and the GFP gene for monitoring viral replication. The hTERT is the catalytic subunit of telomerase, which is highly active in cancer cells, but is quiescent in most normal somatic cells. When the human lung cancer cell line H1299 was infected with OBP-401, the virus replicated in tumor cells and showed strong green signals. In contrast, infection of OBP-401 did not show any signals in normal cells such as fibroblasts. We also found that established subcutaneous tumors could be visualized following intratumoral injection of OBP-401. H1299 human lung tumors transplanted into BALB/c nu/nu mice were intratumorally injected with 1 x 10^8 plaque forming units (PFU) of OBP-401. Within 24 hours of treatment, the fluorescence of the expressed GFP became visible by 3CCD camera in these tumors. Moreover, intrathoracic administration of OBP-401 could visualize disseminated A549 tumor nodules in mice following intrathoracic implantation. Our results indicate that intratumoral or intrathoracic injection of OBP-401 might be a useful diagnostic method that provides a foundation for future clinical application.