Clinical Research Papers:
Optical imaging of gastric cancer with near-infrared heptamethine carbocyanine fluorescence dyes
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Ningning Zhao1,*, Caiqin Zhang1,*, Yong Zhao1, Bing Bai1, Jiaze An1, Hai Zhang1, Jason Boyang Wu2, Changhong Shi1
1Laboratory Animal Center, the Fourth Military Medical University, Xi’an, Shaanxi 710032, China
2Uro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
*These authors have contributed equally to this work
Changhong Shi, email: email@example.com
Jason Boyang Wu, email: BoyangJason.Wu@cshs.org
Keywords: near-infrared fluorescence, heptamethine carbocyanine dyes, gastric cancer, patient-derived tumor xenograft, HIF1α
Received: February 18, 2016 Accepted: May 26, 2016 Published: June 14, 2016
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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