In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus
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.
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The mouse colorectal tumor model shows para-arotic lymph node metastasis after implantation, confirmed histologically.
“This mouse model shows para-arotic lymph node metastasis after implantation, which was histologically confirmed.”
From Understanding and exploiting <i>hTERT</i> promoter regulation for diagnosis and treatment of human cancers (2008) · cites this paper as [116]
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- Authors
- 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.
- Affiliations
- Okayama University (JP)
- Kanazawa University (JP)
- National Institute of Biomedical Innovation (JP)
- Oncolys BioPharma (Japan) (JP)
- Corresponding author
- Fujiwara, Toshiyoshi
- ORCID
- Venue
- Nature Medicine
- Published
- 2006-10
- Volume
- 12
- Issue
- 10
- Pages
- 1213-1219
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2144584725
- Cited by
- 179
- References
- 29
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 6 · 2022: 4 · 2021: 14 · 2020: 8 · 2019: 4 · 2018: 4 · 2017: 7 · 2016: 6 · 2015: 12 · 2014: 7 · 2013: 15 · 2012: 17
- FWCI
- 6.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Okayama University Scientific Achievement Repository (Okayama University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- lymph node metastasis, in vivo tumor imaging, telomerase, human telomerase reverse transcriptase, replication-competent adenovirus, green fluorescent protein, intratumoral injection, colorectal cancer, surgical navigation, nude mice
- MeSH terms
- Adenoviridae, Animals, Aorta, Disease Models, Animal, Female, Humans, Lymphatic Metastasis, Mice, Inbred BALB C, Mice, Nude, Neoplasm Metastasis, Neoplasm Transplantation, Microscopy, Video, Telomerase, Green Fluorescent Proteins, Mice
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