Zhang Caiqin, Zhao Yong, Zhang He, Chen Xue, Zhao Ningning, Tan Dengxu, Zhang Hai, Shi Changhong
Laboratory Animal Center, the Fourth Military Medical University, Xi'an 710032, China.
Int J Mol Sci. 2017 Jun 21;18(6):1332. doi: 10.3390/ijms18061332.
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.
近红外荧光（NIRF）成像在无创肿瘤成像中具有广泛应用的强大潜力。吲哚菁绿（ICG）是唯一经美国食品药品监督管理局（FDA）批准用于临床诊断的NIRF染料；然而，它不稳定且对肿瘤的靶向性较差。DZ-1是一种新型的七甲川花菁NIRF染料，适用于成像和肿瘤靶向。在此，我们比较了DZ-1和ICG的荧光强度及代谢情况。此外，我们使用培养的肝癌（HCC）细胞系、肝癌裸鼠皮下异种移植模型和兔原位移植模型，测定了它们靶向肿瘤细胞的特异性和能力。我们发现DZ-1在肿瘤组织中蓄积，并在皮下和原位模型中特异性识别肝癌。DZ-1的NIRF强度比ICG强一个数量级，并且在兔模型中DZ-1在术中显示出优异的肿瘤靶向性。重要的是，ICG在肿瘤部位以及肝脏和肾脏中蓄积。此外，DZ-1类似物-吉西他滨偶联物（NIRG）在肝癌患者来源的异种移植（PDX）小鼠中表现出类似的肿瘤特异性靶向和成像特性，包括抑制肿瘤生长。与ICG相比，DZ-1和NIRG表现出卓越的肿瘤靶向特异性。我们表明DZ-1是一种用于肝癌特异性成像、靶向和治疗的有效分子探针。
