Open AccessFluorescence tumor imaging by i.v. administered indocyanine green in a mouse model of colitis‐associated colon cancer
Author(s) -
Nagahara Rei,
Onda Nobuhiko,
Yamashita Susumu,
Kojima Miho,
Inohana Mari,
Eguchi Ayumi,
Nakamura Misato,
Matsumoto Shinya,
Yoshida Toshinori,
Shibutani Makoto
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13564
Subject(s) - azoxymethane , pathology , indocyanine green , colorectal cancer , ex vivo , in vivo , vascular permeability , fluorescence lifetime imaging microscopy , medicine , chemistry , cancer research , cancer , biology , fluorescence , physics , microbiology and biotechnology , quantum mechanics
Fluorescence tumor imaging using exogenous fluorescent tumor‐targeting agents has potential to improve early tumor detection. The fluorescent contrast agent indocyanine green ( ICG ) is used in medical diagnostics. The aim of the present study is to investigate the tumor imaging capability and the imaging mechanism of i.v. administered ICG in a mouse model of colitis‐associated colon cancer. To do this, an azoxymethane/dextran sodium sulfate‐induced colon cancer mouse model was used. Ex vivo imaging experiments were carried out 1 hour after i.v. injection of ICG . The ICG fluorescence was observed in the colon tumor tissues, with sufficient tumor to normal tissue ratio, correlating with tumor malignancy. In the tumor tissues, ICG fluorescence was localized in the vascular interstitial tissue. Immunofluorescence microscopy revealed that tumor cells formed tight junctions normally, suggesting an inability of tumor cellular uptake of ICG . In contrast, tumor tissues increased the CD 31‐immunoreactive endothelial cell area, and accumulated stromal cells immunoreactive for COX ‐2 and tumor cell population immunoreactive for inducible nitric oxide synthase. In vivo vascular permeability assay revealed that prostaglandin E 2 promoted the endothelial cell permeability of ICG . In conclusion, our data indicated that fluorescence contrast‐enhanced imaging following i.v. administered ICG can be applied to the detection of colon tumors in a mouse colitis‐associated colon cancer model. The tumor tissue preference of ICG in the present model can be attributed to the enhanced vascular leakage of ICG involving inflammatory mediators, such as COX ‐2 and inducible nitric oxide synthase, in conjunction with increased tumor vascularity.