In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus.
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.
Kishimoto
Hiroyuki
H
Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Kojima
Toru
T
Watanabe
Yuichi
Y
Kagawa
Shunsuke
S
Fujiwara
Toshiya
T
Uno
Futoshi
F
Teraishi
Fuminori
F
Kyo
Satoru
S
Mizuguchi
Hiroyuki
H
Hashimoto
Yuuri
Y
Urata
Yasuo
Y
Tanaka
Noriaki
N
Fujiwara
Toshiyoshi
T
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001011:Aorta / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018715:Microscopy, Video / Q000379:methods*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D019098:Telomerase / Q000378:metabolism*
D049452:Green Fluorescent Proteins; D019098:Telomerase