In vivo internal tumor illumination by telomerase-dependent adenoviral GFP for precise surgical navigation

Hiroyuki Kishimoto, Ming Zhao, Katsuhiro Hayashi, Yasuo Urata, Noriaki Tanaka, Toshiyoshi Fujiwara, Sheldon Penman, Robert M. Hoffman

Research output: Contribution to journalArticle

124 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)14514-14517
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number34
DOIs
Publication statusPublished - Aug 25 2009

Keywords

  • Adenovirus
  • Green fluorescent protein
  • Metastasis

ASJC Scopus subject areas

  • General

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