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 Teranishi, Satoru Kyo, Hiroyuki Mizuguchi, Yuuri Hashimoto, Yasuo Urata, Noriaki Tanaka, Toshiyoshi Fujiwara

Research output: Contribution to journalArticle

130 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

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Telomerase
Adenoviridae
Tumors
Green Fluorescent Proteins
Lymph Nodes
Neoplasm Metastasis
Imaging techniques
Neoplasms
Genes
Anatomic Models
Viral Genes
Magnetic resonance
Rectum
Laparotomy
Tomography
Navigation
Color
Fluorescence
Cameras
Magnetic Resonance Imaging

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus. / Kishimoto, Hiroyuki; Kojima, Toru; Watanabe, Yuichi; Kagawa, Shunsuke; Fujiwara, Toshiya; Uno, Futoshi; Teranishi, Fuminori; Kyo, Satoru; Mizuguchi, Hiroyuki; Hashimoto, Yuuri; Urata, Yasuo; Tanaka, Noriaki; Fujiwara, Toshiyoshi.

In: Nature Medicine, Vol. 12, No. 10, 10.2006, p. 1213-1219.

Research output: Contribution to journalArticle

Kishimoto, H, Kojima, T, Watanabe, Y, Kagawa, S, Fujiwara, T, Uno, F, Teranishi, 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, vol. 12, no. 10, pp. 1213-1219. https://doi.org/10.1038/nm1404
Kishimoto, Hiroyuki ; Kojima, Toru ; Watanabe, Yuichi ; Kagawa, Shunsuke ; Fujiwara, Toshiya ; Uno, Futoshi ; Teranishi, Fuminori ; Kyo, Satoru ; Mizuguchi, Hiroyuki ; Hashimoto, Yuuri ; Urata, Yasuo ; Tanaka, Noriaki ; Fujiwara, Toshiyoshi. / In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus. In: Nature Medicine. 2006 ; Vol. 12, No. 10. pp. 1213-1219.
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