Molecular imaging using an anti-human tissue factor monoclonal antibody in an orthotopic glioma xenograft model.

Molecular imaging using an anti-human tissue factor monoclonal antibody in an orthotopic glioma xenograft model.
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DOI:
10.1038/s41598-017-12563-5
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发表时间:
2017-09-26
期刊:
影响因子:
4.6
通讯作者:
Matsumura Y
Matsumura Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Takashima H;Tsuji AB;Saga T;Yasunaga M;Koga Y;Kuroda JI;Yano S;Kuratsu JI;Matsumura Y

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神经胶质瘤的核医学成像检查已被引入临床实践,以评估恶性程度和确定活检的采样位置。然而,这些模式有一些局限性。组织因子(TF)在各种类型的癌症中过表达,包括神经胶质瘤。因此,我们产生了抗人TF单克隆抗体(mAb)克隆1849。在本研究中,使用抗TF 1849单克隆抗体对胶质瘤标本进行免疫组化显示,TF在胶质瘤中的表达与基于世界卫生组织(WHO)分类的恶性程度成比例增加,并且TF在坏死和假性扁平化细胞中显著表达,这是多形性胶质母细胞瘤(GBM)的组织病理学标志。此外,在荧光和单光子发射计算机断层扫描/计算机断层扫描(SPECT/CT)成像研究中,抗TF 1849 IgG在TF过表达的小鼠颅内肿瘤中有效蓄积。尽管未来临床使用111 In标记的抗TF 1849 IgG的免疫SPECT需要进一步研究,但免疫SPECT可能代表一种独特的成像模式,其可以显示胶质瘤的生物学特征,与使用现有成像模式获得的生物学特征不同,并且可能有助于评估恶性程度并确定胶质瘤患者活检的采样位置,尤其是GBM。
Nuclear medicine examinations for imaging gliomas have been introduced into clinical practice to evaluate the grade of malignancy and determine sampling locations for biopsies. However, these modalities have some limitations. Tissue factor (TF) is overexpressed in various types of cancers, including gliomas. We thus generated an anti-human TF monoclonal antibody (mAb) clone 1849. In the present study, immunohistochemistry performed on glioma specimens using anti-TF 1849 mAb showed that TF expression in gliomas increased in proportion to the grade of malignancy based on the World Health Organization (WHO) classification, and TF was remarkably expressed in necrosis and pseudopalisading cells, the histopathological hallmarks of glioblastoma multiforme (GBM). Furthermore, in both fluorescence and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging studies, anti-TF 1849 IgG efficiently accumulated in TF-overexpressing intracranial tumours in mice. Although further investigation is required for a future clinical use of immuno-SPECT with 111In-labelled anti-TF 1849 IgG, the immuno-SPECT may represent a unique imaging modality that can visualize the biological characteristics of gliomas differently from those obtained using the existing imaging modalities and may be useful to evaluate the grade of malignancy and determine sampling locations for biopsies in patients with glioma, particularly GBM.
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