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Updated: Jun 20, 2026
Dual Bioluminescence Imaging of Tumor Progression and Angiogenesis
Published on: August 1, 2019
In vivo internal tumor illumination by telomerase-dependent adenoviral GFP for precise surgical navigation
Hiroyuki Kishimoto1, Ming Zhao, Katsuhiro Hayashi
1AntiCancer, Inc, San Diego, CA 92111, USA.
Abstract:
Cancer surgery requires the complete and precise identification of malignant tissue margins including the smallest disseminated lesions. Internal green fluorescent protein (GFP) fluorescence can intensely illuminate even single cells but requires GFP sequence transcription within the cell. Introducing and selectively activating the GFP gene in malignant tissue in vivo is made possible by the development of OBP-401, a telomerase-dependent, replication-competent adenovirus expressing GFP. This potentially powerful adjunct to surgical navigation was demonstrated in 2 nude mouse models that represent difficult surgical challenges--the resection of widely disseminated cancer. HCT-116, a model of intraperitoneal disseminated human colon cancer, was labeled by virus injection into the peritoneal cavity. A549, a model of pleural dissemination of human lung cancer, was labeled by virus administered into the pleural cavity. Only the malignant tissue fluoresced brightly in both models. In the intraperitoneal model of disseminated cancer, fluorescence-guided surgery enabled resection of all tumor nodules labeled with GFP by OBP-401. The data in this report suggest that adenoviral-GFP labeling tumors in patients can enable fluorescence-guided surgical navigation.
Insights
A novel adenoviral vector, OBP-401, enables precise in vivo cancer cell labeling with green fluorescent protein (GFP). This facilitates fluorescence-guided surgery, improving the complete resection of disseminated tumors in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Surgical Innovation
Background:
- Accurate identification of malignant tissue margins and disseminated lesions is critical for effective cancer surgery.
- Current methods may struggle with detecting the smallest cancerous cells, potentially leading to incomplete tumor removal.
- Green fluorescent protein (GFP) offers intense cellular illumination but requires in vivo gene expression.
Purpose of the Study:
- To evaluate the efficacy of OBP-401, a telomerase-dependent adenovirus expressing GFP, for in vivo tumor labeling.
- To assess the utility of OBP-401 in guiding surgical resection of widely disseminated cancers in preclinical models.
- To determine the potential of adenoviral-GFP labeling for enhancing fluorescence-guided surgical navigation in patients.
Main Methods:
- Utilized two nude mouse models: HCT-116 (human colon cancer) for intraperitoneal dissemination and A549 (human lung cancer) for pleural dissemination.
- Administered OBP-401 via intraperitoneal or intrapleural injection to label disseminated tumors.
- Performed fluorescence-guided surgery to resect GFP-labeled tumor nodules.
Main Results:
- OBP-401 selectively and intensely labeled malignant tissues in both intraperitoneal and pleural dissemination models.
- In the intraperitoneal model, fluorescence-guided surgery successfully resected all GFP-labeled tumor nodules.
- Only cancerous tissues exhibited bright fluorescence, distinguishing them from surrounding healthy tissue.
Conclusions:
- Adenoviral-mediated GFP expression via OBP-401 is a viable strategy for in vivo tumor labeling.
- OBP-401 facilitates precise surgical navigation and complete tumor resection in models of disseminated cancer.
- This approach holds promise for improving surgical outcomes in cancer patients through enhanced intraoperative visualization.
