Affibody-Indocyanine Green Based Contrast Agent for Photoacoustic and Fluorescence Molecular Imaging of B7-H3 Expression in Breast Cancer

Affibody-Indocyanine Green Based Contrast Agent for Photoacoustic and Fluorescence Molecular Imaging of B7-H3 Expression in Breast Cancer
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DOI:
10.1021/acs.bioconjchem.9b00239
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发表时间:
2019-06-01
影响因子:
4.7
通讯作者:
Wilson, Katheryne E.
Wilson, Katheryne E.
中科院分区:
化学2区
文献类型:
--
作者:
Bam, Rakesh;Laffey, Makenna;Wilson, Katheryne E.

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光谱光声(SpA)分子成像在识别针对特定标志物的外源性造影剂方面具有很高的潜力。抗体染料结合物最近被广泛用于临床前水疗和其他光学成像方式,用于高度特异的乳腺癌分子成像。然而,基于抗体的试剂存在循环时间长的问题,这限制了图像的特异性。在这里,一种小的蛋白质支架,附着体(Aby),连接到吲哚青绿(ICG),一种近红外荧光染料,作为靶向分子成像探针的有效性被证明。特别是,B7-H3(CD276),一种在乳腺癌中表达的细胞受体,通过SPA和荧光分子成像进行成像,以区分小鼠浸润性肿瘤和正常腺体。与B7-H3特异性Aby结合的ICG(Aby(B7-H3)-ICG)在小鼠乳腺肿瘤中显示出明显高于正常腺体的信号。ABY(B7-H3)-ICG是用于乳腺癌检测的分子SPA成像的引人注目的支架。
Spectroscopic photoacoustic (sPA) molecular imaging has high potential for identification of exogenous contrast agents targeted to specific markers. Antibody dye conjugates have recently been used extensively for preclinical sPA and other optical imaging modalities for highly specific molecular imaging of breast cancer. However, antibody-based agents suffer from long circulation times that limit image specificity. Here, the efficacy of a small protein scaffold, the affibody (ABY), conjugated to indocyanine green (ICG), a near-infrared fluorescence dye, as a targeted molecular imaging probe is demonstrated. In particular, B7-H3 (CD276), a cellular receptor expressed in breast cancer, was imaged via sPA and fluorescence molecular imaging to differentiate invasive tumors from normal glands in mice. Administration of ICG conjugated to an ABY specific to B7-H3 (ABY(B7-H3)-ICG) showed significantly higher signal in mammary tumors compared to normal glands of mice. ABY(B7-H3)-ICG is a compelling scaffold for molecular sPA imaging for breast cancer detection.