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

Hiroyuki Kishimoto, Toru Kojima, Yuichi Watanabe, Shunsuke Kagawa, Toshiya Fujiwara, Futoshi Uno, Fuminori Teraishi, Satoru Kyo, Hiroyuki Mizuguchi, Yuuri Hashimoto, Yasuo Urata, Noriaki Tanaka, Toshiyoshi Fujiwara

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136 Citations (Scopus)

Abstract

Currently available methods for detection of tumors in vivo such as computed tomography and magnetic resonance imaging are not specific for tumors. Here we describe a new approach for visualizing tumors whose fluorescence can be detected using telomerase-specific replication-competent adenovirus expressing green fluorescent protein (GFP) (OBP-401). OBP-401 contains the replication cassette, in which the human telomerase reverse transcriptase (hTERT) promoter drives expression of E1 genes, and the GFP gene for monitoring viral replication. When OBP-401 was intratumorally injected into HT29 tumors orthotopically implanted into the rectum in BALB/c nu/nu mice, para-aortic lymph node metastasis could be visualized at laparotomy under a three-chip color cooled charged-coupled device camera. Our results indicate that OBP-401 causes viral spread into the regional lymphatic area and selectively replicates in neoplastic lesions, resulting in GFP expression in metastatic lymph nodes. This technology is adaptable to detect lymph node metastasis in vivo as a preclinical model of surgical navigation.

Original languageEnglish
Pages (from-to)1213-1219
Number of pages7
JournalNature Medicine
Volume12
Issue number10
DOIs
Publication statusPublished - Oct 2006

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Kishimoto, H., Kojima, T., Watanabe, Y., Kagawa, S., Fujiwara, T., Uno, F., Teraishi, F., Kyo, S., Mizuguchi, H., Hashimoto, Y., Urata, Y., Tanaka, N., & Fujiwara, T. (2006). In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus. Nature Medicine, 12(10), 1213-1219. https://doi.org/10.1038/nm1404