Real-time monitoring of microdistribution of antibody-photon absorber conjugates during photoimmunotherapy in vivo.
Real-time monitoring of microdistribution of antibody-photon absorber conjugates during photoimmunotherapy in vivo.
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DOI：
10.1016/j.jconrel.2017.06.004
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发表时间：
2017-08-28
期刊：
影响因子：
--
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Tang Q;Nagaya T;Liu Y;Lin J;Sato K;Kobayashi H;Chen Y
光免疫疗法（PIT）是一种新兴的低副作用癌症治疗方法，基于单克隆抗体（mAb）与近红外（NIR）酞菁染料IRDye 700DX偶联。IR700是荧光的，可以用作显像剂，也有光毒性。它在近红外光照射后诱导细胞快速死亡。PIT诱导高度选择性的癌细胞死亡，同时使大多数肿瘤血管不受伤害，导致一种称为超增强渗透和保留（SUPR）的效果。SUPR显著提高了抗癌药物的有效性。目前，基于宏观荧光反射成像的IR700荧光信号监测PIT的治疗效果。然而，这种技术缺乏分辨率和深度信息来揭示肿瘤内mAb-IR700分布的异质性。我们将传统的荧光成像显微镜与两束成像纤维束（~0.85 mm）相结合，应用了一种微创双通道荧光纤维成像系统。该方法实时监测PIT期间肿瘤内不同位置（如肿瘤表面与肿瘤深部）的mAb-IR700分布和治疗效果。这使得体内治疗效果和治疗方案的评估成为可能。PIT后肿瘤表面IR700荧光强度平均恢复为91.50%，深部肿瘤IR700荧光强度平均恢复为100.63%。为了验证结果，我们还使用双光子显微镜联合微棱镜记录了PIT期间不同肿瘤深度的mAb-IR700分布和绿色荧光蛋白（GFP）的荧光强度。PIT治疗后，肿瘤深部IR700荧光恢复明显高于肿瘤表面。这种现象可以解释为NIR-PIT后血管通透性立即增加。肿瘤表面GFP荧光强度较深部肿瘤和对照组（无PIT）明显下降。
Photoimmunotherapy (PIT) is an emerging low side effect cancer therapy based on a monoclonal antibody (mAb) conjugated with a near-infrared (NIR) phthalocyanine dye IRDye 700DX. IR700 is fluorescent, can be used as an imaging agent, and also is phototoxic. It induces rapid cell death after exposure to NIR light. PIT induces highly selective cancer cell death, while leaving most of tumor blood vessels unharmed, leading to an effect called super-enhanced permeability and retention (SUPR). SUPR significantly improves the effectiveness of the anticancer drug. Currently, the therapeutic effects of PIT are monitored using the IR700 fluorescent signal based on macroscopic fluorescence reflectance imagery. This technique, however, lacks the resolution and depth information to reveal the intratumor heterogeneity of mAb-IR700 distribution. We applied a minimally invasive two-channel fluorescence fiber imaging system by combining the traditional fluorescence imaging microscope with two imaging fiber bundles (~0.85 mm). This method monitored mAb-IR700 distribution and therapeutic effects during PIT at different intratumor locations (e.g., tumor surface vs. deep tumor) in situ and in real time simultaneously. This enabled evaluation of the therapeutic effects in vivo and treatment regimens. The average IR700 fluorescence intensity recovery after PIT to the tumor surface is 91.50%, while it is 100.63% in deep tumors. To verify the results, two-photon microscopy combined with a microprism was also used to record the mAb-IR700 distribution and fluorescence intensity of green fluorescent protein (GFP) at different tumor depths during PIT. After PIT treatment, there was significantly higher IR700 fluorescence recovery in deep tumor than in the tumor surface. This phenomenon can be explained by increased vascular permeability immediately after NIR-PIT. Fluorescence intensity of GFP at the tumor surface decreased significantly more compared to that of deep tumor and in controls (no PIT).
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影响因子：
8.8
作者：
Carcenac, M;Dorvillius, M;Pèlegrin, A
通讯作者：
Pèlegrin, A
DOI：
10.1523/jneurosci.2369-11.2011
发表时间：
2011-09-14
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Luo Z;Volkow ND;Heintz N;Pan Y;Du C
通讯作者：
Du C
影响因子：
6.6
作者：
Nagaya, Tadanobu;Nakamura, Yuko;Kobayashi, Hisataka
通讯作者：
Kobayashi, Hisataka
DOI：
10.1038/nri2744
发表时间：
2010-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4
作者：
Parish, CR
通讯作者：
Parish, CR