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Evaluation of Early Therapeutic Effects after Near-Infrared Photoimmunotherapy (NIR-PIT) Using Luciferase–Luciferin Photon-Counting and Fluorescence Imaging
Molecular Pharmaceutics ( IF 4.9 ) Pub Date : 2017-11-22 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00731
Yasuhiro Maruoka 1 , Tadanobu Nagaya 1 , Yuko Nakamura 1 , Kazuhide Sato 1 , Fusa Ogata 1 , Shuhei Okuyama 1 , Peter L. Choyke 1 , Hisataka Kobayashi 1
Affiliation  

Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that induces highly selective immunogenic cell death. It is based on an antibody–photoabsorber conjugate (APC) that is activated by NIR light. The purpose of this study was to investigate the effects of NIR-PIT as measured by luciferase–luciferin photon-counting and fluorescence imaging. Six days after subcutaneous injection of A431-luc-GFP cells tumors formed in a xenograft mouse model. The EGFR-targeting antibody, panitumumab, was conjugated to the photoabsorber, IRDye-700DX (pan–IR700), and was intravenously administered to tumor-bearing mice. Serial luciferase–luciferin photon-counting images and both green fluorescent protein (GFP) and IR700 fluorescence images were obtained from the same mice before and after NIR-PIT treatment (0, 10, 20, 30 min (early phase), and 24, 48 h (late phase) after NIR light exposure). Optical signal intensities were compared for each modality. IR700 fluorescence and luciferase–luciferin photon-counting images showed decreased intensities in both the early and late phases after NIR-PIT (p < 0.01). On the other hand, GFP fluorescence images showed decreased intensities only in the late phase (p < 0.01). In the early phase, GFP fluorescence images showed smaller intensity reductions compared to IR700 fluorescence and luciferase–luciferin photon-counting (p < 0.01), while in the late phase, IR700 fluorescence showed smaller intensity reductions than luciferase–luciferin photon-counting and GFP fluorescence (p < 0.05), due to redistribution of pan–IR700 within the tumor bed. In conclusion, luciferase–luciferin photon-counting imaging is suitable to evaluate early phase NIR-PIT effects, while both luciferase–luciferin photon-counting and GFP reflected later phase effects.

中文翻译:

使用荧光素酶-荧光素光子计数和荧光成像评估近红外光免疫疗法(NIR-PIT)后的早期治疗效果

近红外光免疫疗法(NIR-PIT)是一种新开发的癌症疗法,可诱导高度选择性的免疫原性细胞死亡。它基于被近红外光激活的抗体-光吸收剂偶联物(APC)。本研究的目的是研究通过荧光素酶-荧光素光子计数和荧光成像测量的NIR-PIT的影响。皮下注射A431-luc-GFP细胞六天后,异种移植小鼠模型中形成了肿瘤。靶向EGFR的抗体panitumumab与光吸收剂IRDye-700DX(pan–IR700)偶联,并静脉注射给荷瘤小鼠。连续荧光素酶-荧光素光子计数图像以及绿色荧光蛋白(GFP)和IR700荧光图像均来自于在NIR-PIT处理之前和之后(早期,0、10、20、30分钟,NIR曝光后24、48小时(后期)。比较每种模态的光信号强度。IR700荧光和荧光素酶-荧光素光子计数图像显示,NIR-PIT后早期和晚期强度均降低(p <0.01)。另一方面,GFP荧光图像仅在后期显示强度降低(p <0.01)。与IR700荧光和荧光素酶-荧光素光子计数相比,GFP荧光图像在早期显示强度降低较小(p <0.01),而在后期,IR700荧光的强度降低量小于荧光素酶-荧光素光子计数和GFP强度降低。荧光(p <0.05),这是由于pan-IR700在肿瘤床内的重新分布所致。总之,萤光素酶-萤光素的光子计数成像适合评估早期NIR-PIT效应,而萤光素酶-萤光素的光子计数和GFP均可反映后期相位效应。
更新日期:2017-11-23
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