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Int. J. Mol. Sci. 2017, 18(6), 1332; doi:10.3390/ijms18061332

The Application of Heptamethine Cyanine Dye DZ-1 and Indocyanine Green for Imaging and Targeting in Xenograft Models of Hepatocellular Carcinoma

Laboratory Animal Center, the Fourth Military Medical University, Xi’an 710032, China
These authors contributed equally to this work.
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Received: 10 May 2017 / Revised: 7 June 2017 / Accepted: 18 June 2017 / Published: 21 June 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Near infrared fluorescence (NIRF) imaging has strong potential for widespread use in noninvasive tumor imaging. Indocyanine green (ICG) is the only Food and Drug Administration (FDA) -approved NIRF dye for clinical diagnosis; however, it is unstable and poorly targets tumors. DZ-1 is a novel heptamethine cyanine NIRF dye, suitable for imaging and tumor targeting. Here, we compared the fluorescence intensity and metabolism of DZ-1 and ICG. Additionally, we assayed their specificities and abilities to target tumor cells, using cultured hepatocellular carcinoma (HCC) cell lines, a nude mouse subcutaneous xenograft model of liver cancer, and a rabbit orthotopic transplantation model. We found that DZ-1 accumulates in tumor tissue and specifically recognizes HCC in subcutaneous and orthotopic models. The NIRF intensity of DZ-1 was one order of magnitude stronger than that of ICG, and DZ-1 showed excellent intraoperative tumor targeting in the rabbit model. Importantly, ICG accumulated at tumor sites, as well as in the liver and kidney. Furthermore, DZ-1 analog-gemcitabine conjugate (NIRG) exhibited similar tumor-specific targeting and imaging properties, including inhibition of tumor growth, in HCC patient-derived xenograft (PDX) mice. DZ-1 and NIRG demonstrated superior tumor-targeting specificity, compared to ICG. We show that DZ-1 is an effective molecular probe for specific imaging, targeting, and therapy in HCC. View Full-Text
Keywords: near-infrared fluorescence; heptamethine cyanine dyes; hepatocellular carcinoma; xenograft model; optical imaging; intraoperative navigation near-infrared fluorescence; heptamethine cyanine dyes; hepatocellular carcinoma; xenograft model; optical imaging; intraoperative navigation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Zhang, C.; Zhao, Y.; Zhang, H.; Chen, X.; Zhao, N.; Tan, D.; Zhang, H.; Shi, C. The Application of Heptamethine Cyanine Dye DZ-1 and Indocyanine Green for Imaging and Targeting in Xenograft Models of Hepatocellular Carcinoma. Int. J. Mol. Sci. 2017, 18, 1332.

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