Intraoperative localization of lymph node metastases with a replication-competent herpes simplex virus

Area of Science:

• Oncology
• Virology
• Surgical Innovation

Background:

• Lymph node status is critical for prognosis in mesothelioma and thoracic cancers.
• Accurate localization of lymph node metastases is essential for surgical planning and patient selection.
• Current methods for metastasis detection can be limited in intraoperative accuracy.

Purpose of the Study:

• To investigate the use of a modified herpes simplex virus (NV1066) for intraoperative detection of lymph node metastases.
• To assess cancer cell-specific infection and green fluorescent protein (GFP) expression by NV1066.
• To evaluate the feasibility of fluorescent imaging for localizing metastases in vivo.

Main Methods:

• Human mesothelioma cell lines were infected with NV1066 (HSV-GFP).
• In vitro assessments included infection, GFP expression, viral replication, and cytotoxicity.
• Murine models of lymphatic metastasis were created, and lymph node metastases were localized using fluorescent thoracoscopy and laparoscopy.

Main Results:

• NV1066 demonstrated efficient cancer cell-specific infection, replication, and GFP expression in vitro.
• Intraoperative fluorescent imaging successfully located lymph node metastases in vivo.
• Histology and immunohistochemistry confirmed the presence of metastases and viral infection in GFP-expressing regions.

Conclusions:

• Herpes virus-mediated GFP expression enables precise intraoperative localization of lymph node metastases.
• Integration of GFP-detecting filters into surgical scopes can enhance the biopsy of metastatic lymph nodes.
• This approach offers a promising tool for improving surgical outcomes in thoracic malignancies.