Research Papers:

Heptamethine carbocyanine DZ-1 dye for near-infrared fluorescence imaging of hepatocellular carcinoma

Jiaze An, Ningning Zhao, Caiqin Zhang, Yong Zhao, Dengxu Tan, Ya Zhao, Bing Bai, Hai Zhang, Boyang Jason Wu and Changhong Shi _

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Oncotarget. 2017; 8:56880-56892. https://doi.org/10.18632/oncotarget.18131

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Jiaze An1,2,*, Ningning Zhao1,*, Caiqin Zhang1, Yong Zhao1, Dengxu Tan1, Ya Zhao1, Bing Bai1, Hai Zhang1, Boyang Jason Wu3,** and Changhong Shi1,**

1Laboratory Animal Center, The Fourth Military Medical University, Xi’an, Shaanxi 710032, China

2Department of Hepatobiliary and Pancreaticosplenic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, China

3Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99210, USA

*These authors contributed equally to this work

**Joint corresponding authors

Correspondence to:

Changhong Shi, email: [email protected]

Boyang Jason Wu, email: [email protected]

Keywords: heptamethine carbocyanine, hepatocellular carcinoma, HIF1α, near-infrared fluorescence, organic anion-transporting polypeptide

Received: February 28, 2017     Accepted: April 17, 2017     Published: May 24, 2017


Near-infrared fluorescence (NIRF) dyes have recently emerged as promising tools for non-invasive imaging of different types of cancers. Here, we explored the potential utility of a NIRF DZ-1 dye, with dual imaging and tumour targeting functions, in hepatocellular carcinoma (HCC). We showed the preferential uptake of DZ-1 by HCC cells in vitro and in derived subcutaneous/orthotopic tumour xenografts, accompanied by a minimal effect on normal cells. DZ-1 simplified tumour growth profiling as well, since we were able to correlate NIRF signals with tumour volume and/or tumour-emitting luminescence in mice. Using both orthotopic tumour transplantation and cirrhosis models in parallel, we demonstrated the ability of DZ-1 to differentiate liver tumour from cirrhosis. DZ-1 showed superiority in HCC imaging over indocyanine green by demonstrating significantly enhanced tumour-targeting specificity. At the cellular level, DZ-1 was mainly retained in mitochondria and lysosomes. Additionally, DZ-1 fluorescence spectroscopy has been used for the intraoperative navigation of rabbit liver cancer, to determine surgical margins. We showed that tumor hypoxia and select organic anion-transporting polypeptide genes mediate NIRF dye uptake in HCC, which was supported by clinical evidence. All these findings represent the first evidence that DZ-1 is an effective molecular probe for tumour-specific imaging in HCC, and provide insights into the development of a new generation of imaging agents for intraoperative guidance of cancer surgery.

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