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.
Highlights
Near-infrared fluorescence (NIRF) imaging is a promising tool for noninvasive tumor imaging [1,2]
NIRF dye indocyanine green (ICG) can be quickly combined with plasma protein, distributed in systemic blood vessels, and efficiently and selectively taken up by liver cells with rapid blood circulation, which aids in diagnosis of liver fibrosis and cirrhosis and gastrointestinal vascular defects [21,22,23,24]
The conventional NIR dye needs to be labeled with peptides or a specific antigen marker, which facilitates targeting, only a part of the tumor can be identified, and the chemical combination often affects the stability of the target molecule [26,27]
Summary
Near-infrared fluorescence (NIRF) imaging is a promising tool for noninvasive tumor imaging [1,2]. Our research group has synthesized and screened a series of heptamethine cyanine NIRF dyes, including IR-783 and MHI-148 [12,13] These compounds displayed tumor targeting capabilities, in both tumor cells and various nude mouse xenograft models [14,15]. These dyes were conjugated with a vIantr.iJe. Mtyol.oSfcia. The water solubility oOf utrhreesseeardcyhegsroiuspphoaos rs— yntahlelsimzeudsatnbdescdreiesnseodlvaesderiiens odf ihmepettahmyelthsiunelfcoyxaindineeaNnIdRFtdhyeens, diluted with phionsclpuhdaintge-IbRu-7f8fe3raenddsMalHinI-e14fo8r[1i2n,t1r3a].pTehreitsoenceoamlpionujencdtsiodnispdluayreindgtuinmovrivtaorgiemtianggicnagpaabpilpitliiecsa, tinions [18] Both tumor cells and various nude mouse xenograft models [14,15]. SSttrroonnggflfluuoorreesscceennttssiiggnnaallwwaassddeetteecctteeddaattssuubbccuuttaanneeoouussttuummoorrssitiete; ;(D(D–,FF)) IInnhhiibbiittiioonn ooff NNIIRRGGoonn tthhee ttuummoorr ggrroowwtthh ffrroomm lliivveerr ccaanncceerr PPDDXX mmoouussee,, iinncclluuddiinngg CC6644000033,, CC3344556666,, aanndd BB6666887733.. dd rreepprreesseennttss tthhee ttrreeaattmmeennttttiimmee
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
