Role of Fluorophore Charge on the In Vivo Optical Imaging Properties of Near-Infrared Cyanine Dye/Monoclonal Antibody Conjugates
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- 作者：Kazuhide Sato ; Alexander P. Gorka ; Tadanobu Nagaya ; Megan S. Michie ; Roger R. Nani ; Yuko Nakamura ; Vince L. Coble ; Olga V. Vasalatiy ; Rolf E. Swenson ; Peter L. Choyke ; Martin J. Schnermann ; Hisataka Kobayashi
- 刊名：Bioconjugate Chemistry
- 出版年：2016
- 出版时间：February 17, 2016
- 年：2016
- 卷：27
- 期：2
- 页码：404-413
- 全文大小：695K
- ISSN：1520-4812
文摘
Near-infrared (NIR) fluorophores have several advantages over visible-light fluorophores, including superior light penetration in tissue and lower autofluorescence. We recently demonstrated that a new class of NIR cyanine dyes containing a novel C4′-O-alkyl linker exhibit greater chemical stability and excellent optical properties relative to existing C4′-O-aryl variants. We synthesized two NIR cyanine dyes with the same core structure but different indolenine substituents: FNIR-774 bearing four sulfonate groups and FNIR-Z-759 bearing a combination of two sulfonates and two quaternary ammonium cations, resulting in an anionic (−3) or monocationic (+1) charge, respectively. In this study, we compare the in vitro and in vivo optical imaging properties of monoclonal antibody (mAb) conjugates of FNIR-774 and FNIR-Z-759 with panitumumab (pan) at antibody-to-dye ratios of 1:2 or 1:5. Conjugates of both dyes demonstrated similar quenching capacity, stability, and brightness in target cells in vitro. However, FNIR-Z-759 conjugates showed significantly lower background in mice, resulting in higher tumor-to-background ratio. Thus, FNIR-Z-759 conjugates appear to have superior in vivo imaging characteristics compared with FNIR-774 conjugates, especially in the abdominal region, regardless of the dye-mAb ratio. These results suggest that zwitterionic cyanine dyes are a promising class of fluorophores for improving in vivo optical imaging with antibody–NIR dye conjugates.