title: Optical imaging of gastric cancer with near-infrared heptamethine carbocyanine fluorescence dyes.
abstract: Near-infrared fluorescence (NIRF) imaging agents are promising tools for noninvasive cancer imaging. Here, we explored the tumor-specific targeting ability of NIRF heptamethine carbocyanine MHI-148 dye in cultured gastric cancer cells, gastric cancer cell-derived and patient-derived tumor xenograft (PDX) models. We show that the NIRF dye specifically accumulated in tumor regions of both xenograft models, suggesting the potential utility of the dye for tumor-specific imaging and targeting in gastric cancer. We also demonstrated significant correlations between NIRF signal intensity and tumor volume in PDX models. Mechanistically, the higher cellular uptake of MHI-148 in gastric cancer cells than in normal cells was stimulated by hypoxia and activation of a group of organic anion-transporting polypeptide (OATP) genes. Importantly, this NIRF dye was not retained in inflammatory stomach tissues induced by gastric ulcer in mice. In addition, fresh clinical gastric tumor specimens, when perfused with NIR dye, exhibited increased uptake of NIR dye in situ. Together, these results show the possibility of using NIRF dyes as novel candidate agents for clinical imaging and detection of gastric cancer.
authors.affiliation: Laboratory Animal Center, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Laboratory Animal Center, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Caiqin
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Laboratory Animal Center, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Laboratory Animal Center, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Bai
authors.affiliation: Laboratory Animal Center, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Jiaze
authors.initials: J
authors.lastname: An
authors.affiliation: Laboratory Animal Center, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Urologic Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Jason Boyang
authors.initials: JB
authors.lastname: Wu
authors.affiliation: Laboratory Animal Center, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Changhong
authors.initials: C
authors.lastname: Shi
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000737:chemistry*; D045744:Cell Line, Tumor; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007249:Inflammation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D061848:Optical Imaging; D013274:Stomach Neoplasms / Q000000981:diagnostic imaging*
chemical_list: D002232:Carbocyanines; D005456:Fluorescent Dyes; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: HIF1α; gastric cancer; heptamethine carbocyanine dyes; near-infrared fluorescence; patient-derived tumor xenograft