Role of Fluorophore Charge on the In Vivo Optical Imaging Properties of Near-Infrared Cyanine Dye/Monoclonal Antibody Conjugates.
Role of Fluorophore Charge on the In Vivo Optical Imaging Properties of Near-Infrared Cyanine Dye/Monoclonal Antibody Conjugates.
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DOI：
10.1021/acs.bioconjchem.5b00492
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发表时间：
2016-02-17
影响因子：
4.7
通讯作者：
Kobayashi H
中科院分区：
文献类型：
--
作者：
Sato K;Gorka AP;Nagaya T;Michie MS;Nani RR;Nakamura Y;Coble VL;Vasalatiy OV;Swenson RE;Choyke PL;Schnermann MJ;Kobayashi H
近红外(NIR)荧光团与可见光荧光团相比有几个优点，包括在组织中具有更好的光穿透性和更低的自发荧光。我们最近证明，与现有的C4‘-O-芳基化合物相比，一类含有新型C4’-O-芳基连接剂的新型近红外菁染料具有更好的化学稳定性和优异的光学性能。我们合成了两个具有相同核心结构但不同吲哚取代基的近红外菁染料：含有四个磺酸盐基团的FNIR-774和含有两个磺酸盐和两个季铵盐阳离子的FNIR-Z-759，分别产生阴离子(−3)或单阳离子(+1)电荷。在这项研究中，我们比较了fNIR-774和fNIR-Z-759与Panitumab(PAN)在抗体与染料比例为1：2或1：5时的单抗(MAb)在体外和体内的光学成像性能。这两种染料的结合物在体外的靶细胞中表现出相似的猝灭能力、稳定性和亮度。然而，FNIR-Z-759结合物在小鼠中表现出显著的低本底，导致更高的肿瘤与本底比。因此，与FNIR-774结合物相比，FNIR-Z-759结合物似乎具有更好的体内成像特性，特别是在腹部，无论染料-mAb比率如何。这些结果表明，两性离子菁染料是一类很有前途的荧光团，可以用来改善抗体-近红外染料结合物的体内光学成像。
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-arlkyl 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-tobackground 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.
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影响因子：
3.1
作者：
Hyun H;Henary M;Gao T;Narayana L;Owens EA;Lee JH;Park G;Wada H;Ashitate Y;Frangioni JV;Choi HS
通讯作者：
Choi HS
影响因子：
3.6
作者：
Lee, Hyeran;Mason, J. Christian;Achilefu, Samuel
通讯作者：
Achilefu, Samuel
基于物理和生物学的下一代分子成像探针的合理化学设计：混合方式，颜色和信号。
影响因子：
46.2
作者：
Kobayashi H;Longmire MR;Ogawa M;Choyke PL
通讯作者：
Choyke PL
影响因子：
7.3
作者：
Njiojob, Costyl N.;Owens, Eric A.;Narayana, Lakshminarayana;Hyun, Hoon;Choi, Hak Soo;Henary, Maged
通讯作者：
Henary, Maged
影响因子：
4
作者：
Li, XM;Wang, JW;Hoffman, RM
通讯作者：
Hoffman, RM