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.