Real-time fluorescence imaging of abdominal, pleural, and lymphatic metastases

Virally-directed fluorescence imaging has the potential to revolutionize intra-operative oncologic staging and tumor resection. Many viruses genetically engineered to specifically infect tumor cells as cancer therapy can be further modified to have a visible marker gene for cancer staging. In this chapter, we describe such a herpes simplex virus (HSV) modified to be detected by fluorescence. Other viruses so designed can be similarly used in cancer detection and staging. Replication-competent, tumor-specific HSV NV1066 expresses green fluorescent protein (GFP) in infected cancer cells. One single dose of NV1066 administered via intratumor, intracavitary, or systemic injection can spread within and across body cavities to target tumor cells while sparing normal tissue cells from infection. Tumors otherwise invisible by conventional laparoscopy appear green with the use of an endoscope equipped with a fluorescent filter. Furthermore, with GFP expression easily visualized by stereomicroscopy, microscopic, and pathologic analysis is significantly enhanced. This chapter addresses NV1066-directed visualization of peritoneal, pleural, and lymphatic metastases. This chapter also provides protocols for the production of tumor models in various body cavities in rodents.