In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus

Area of Science:

• Oncology
• Virology
• Medical Imaging

Background:

• Current in vivo tumor detection methods like CT and MRI lack tumor specificity.
• There is a need for more specific diagnostic tools for detecting tumors and metastases.
• Telomerase is a promising biomarker for cancer, being active in most tumor cells but not in normal cells.

Purpose of the Study:

• To develop and evaluate a novel tumor visualization method using a telomerase-specific oncolytic adenovirus.
• To assess the potential of OBP-401 for detecting lymph node metastasis in a preclinical model.

Main Methods:

• Development of OBP-401, a replication-competent adenovirus engineered with a human telomerase reverse transcriptase (hTERT) promoter driving E1 gene and green fluorescent protein (GFP) expression.
• Intratumoral injection of OBP-401 into HT29 tumors orthotopically implanted in mice.
• Visualization of viral replication and tumor spread using fluorescence detection under laparotomy.

Main Results:

• OBP-401 demonstrated selective replication in neoplastic lesions.
• Intratumoral injection led to viral spread into the regional lymphatic system.
• Para-aortic lymph node metastasis was successfully visualized via GFP expression in metastatic lymph nodes.
• The method allowed for in vivo detection of lymph node metastasis.

Conclusions:

• Telomerase-specific adenovirus OBP-401 enables selective tumor visualization and detection of lymph node metastasis.
• This technology holds promise as a preclinical model for surgical navigation and cancer detection.
• OBP-401 represents a significant advancement in targeted cancer imaging and diagnostics.