3D mesoscopic fluorescence tomography for imaging micro-distribution of antibody-photon absorber conjugates during near infrared photoimmunotherapy in vivo.

3D mesoscopic fluorescence tomography for imaging micro-distribution of antibody-photon absorber conjugates during near infrared photoimmunotherapy in vivo.
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DOI:
10.1016/j.jconrel.2018.04.027
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发表时间:
2018-06-10
期刊:
Journal of controlled release : official journal of the Controlled Release Society
影响因子:
--
通讯作者:
Chen Y
Chen Y
中科院分区:
其他
文献类型:
--
作者:
Tang Q;Nagaya T;Liu Y;Horng H;Lin J;Sato K;Kobayashi H;Chen Y

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光免疫疗法(PIT)是一种新型的低毒副作用的癌症治疗方法,其基础是将近红外(NIR)酞菁染料IRDye700DX(IR 700)与单抗偶联。IR700不仅是一种荧光显像剂,而且具有光毒性。在近红外光照射下,PIT可以诱导高度选择性的癌细胞死亡,而大部分肿瘤血管不受损伤,从而产生一种被称为超强渗透性和滞留(SUPR)的效应,可以显著提高抗癌药物的疗效。目前,PIT的疗效监测多采用二维宏观荧光反射成像仪,缺乏反映mAb-IR700三维分布的分辨率和深度信息。在本研究中,我们应用包括高分辨率光学相干断层扫描(OCT)和高灵敏度荧光层流光学断层扫描(FLOT)在内的多模式光学成像方法,在原位和体内同时提供肿瘤的三维微结构和mAb-IR700在肿瘤内的微观分布。多波长FLOT还可以提供肿瘤的血管形态。因此,3D FLOT重建图像使我们能够非侵入性地评估IR700在血管和不同肿瘤位置/深度的荧光分布变化,从而能够在体内评估治疗效果并相应地优化治疗方案。单抗-IR700可进入更多的肿瘤区域,这可以解释为近红外光凝后即刻血管通透性增加。用双光子显微镜在肿瘤血管附近的肿瘤表面记录mAb-IR700以验证结果。用于坑中和坑后三维微环境监测的多模型光学成像方案
As a novel low-side-effect cancer therapy, photo-immunotherapy (PIT) is based on conjugating monoclonal antibody (mAb) with a near-infrared (NIR) phthalocyanine dye IRDye700DX (IR 700). IR700 is not only fluorescent to be used as an imaging agent, but also phototoxic. When illuminating with NIR light, PIT can induce highly-selective cancer cell death while leaving most of tumor blood vessels unharmed, leading to an effect termed super-enhanced permeability and retention (SUPR), which can significantly improve the effectiveness of anti-cancer drug. Currently, the therapeutic effects of PIT are monitored using 2D macroscopic fluorescence reflectance imager, which lacks the resolution and depth information to reveal the 3D distribution of mAb-IR700. In the study, we applied a multi-modal optical imaging approach including high-resolution optical coherence tomography (OCT) and high-sensitivity fluorescence laminar optical tomography (FLOT), to provide 3D tumor micro-structure and micro-distribution of mAb-IR700 in the tumor simultaneously during PIT in situ and in vivo. The multi-wavelength FLOT can also provide the blood vessels morphology of the tumor. Thus, the 3D FLOT reconstructed images allow us to evaluate the IR700 fluorescence distribution change with respect to the blood vessels and at different tumor locations/depths non-invasively, thereby enabling evaluation of the therapeutic effects in vivo and optimization of treatment regimens accordingly. The mAb-IR700 can access more tumor areas after PIT treatment, which can be explained by increased vascular permeability immediately after NIR-PIT. Two-photon microscopy was also used to record the mAb-IR700 on the tumor surface near the blood vessels to verify the results. Multi-model optical imaging apporach for monitering 3D micro-enveronment during and after PIT
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