期刊
ONCOTARGET
卷 7, 期 35, 页码 57277-57289出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.10031
关键词
near-infrared fluorescence; heptamethine carbocyanine dyes; gastric cancer; patient-derived tumor xenograft; HIF1 alpha
资金
- National Natural Science Foundation Program [31572340]
- Laboratory Animal Science Funding Program [SYDW2014-002]
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.
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