A versatile technique for the in vivo imaging of human tumor xenografts using near-infrared fluorochrome-conjugated macromolecule probes.
A versatile technique for the in vivo imaging of human tumor xenografts using near-infrared fluorochrome-conjugated macromolecule probes.
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DOI：
10.1371/journal.pone.0082708
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Nakamura M
中科院分区：
文献类型：
--
作者：
Suemizu H;Kawai K;Higuchi Y;Hashimoto H;Ogura T;Itoh T;Sasaki E;Nakamura M
在这里，我们提出了一种通用的方法，用于检测人体肿瘤异种移植在体内，基于增强的渗透性和保留（EPR）的效果，使用近红外（NIR）荧光染料共轭大分子探针。牛血清白蛋白（BSA）和两种免疫球蛋白-抗人类白细胞抗原（HLA）单克隆抗体和同种型对照IgG 2a-标记与XenoLight CF 770荧光染料，并作为近红外共轭大分子探针研究全身成像在各种异种移植小鼠模型。在注射NIR-大分子探针的24小时内，在皮下移植的BxPC-3（人胰腺癌）细胞和HCT 116（结肠直肠癌）细胞中观察到NIR荧光信号，但未观察到来自荧光染料本身或来自NIR缀合的小分子（甘氨酸）注射的信号。通过皮下移植模型中T-HCT 116异种移植物（其中HCT 116细胞稳定表达橙红色荧光蛋白tdTomato）内NIR缀合的免疫球蛋白的定位，证实了肿瘤靶向的准确性。然而，在皮下移植模型中，抗HLA抗体组和同种型对照组之间感兴趣区域的NIR信号强度没有显著差异。因此，体内肿瘤内的抗体积累是基于EPR效应。通过脾内注射T-HCT 116细胞产生的肝转移通过NIR缀合的抗HLA探针而不是通过来自tdTomato报告子的橙红色荧光信号清楚地可视化。该结果证明了NIR探针在增强组织渗透方面优于tdTomato报告蛋白。在另一种异种移植模型中，使用NIR缀合的大分子探针成功地可视化了LC 11-JCK（人非小细胞肺癌）的患者来源的异种移植物（PDX），而没有任何遗传修饰。这些结果表明，NIR缀合的大分子，优选地，抗HLA抗体探针是使用全身成像在实验转移模型中检测人类肿瘤的有价值的工具。
Here, we present a versatile method for detecting human tumor xenografts in vivo, based on the enhanced permeability and retention (EPR) effect, using near-infrared (NIR) fluorochrome-conjugated macromolecule probes. Bovine serum albumin (BSA) and two immunoglobulins—an anti-human leukocyte antigen (HLA) monoclonal antibody and isotype control IgG2a—were labeled with XenoLight CF770 fluorochrome and used as NIR-conjugated macromolecule probes to study whole-body imaging in a variety of xenotransplantation mouse models. NIR fluorescent signals were observed in subcutaneously transplanted BxPC-3 (human pancreatic cancer) cells and HCT 116 (colorectal cancer) cells within 24 h of NIR-macromolecule probe injection, but the signal from the fluorochrome itself or from the NIR-conjugated small molecule (glycine) injection was not observed. The accuracy of tumor targeting was confirmed by the localization of the NIR-conjugated immunoglobulin within the T-HCT 116 xenograft (in which the orange-red fluorescent protein tdTomato was stably expressed by HCT 116 cells) in the subcutaneous transplantation model. However, there was no significant difference in the NIR signal intensity of the region of interest between the anti-HLA antibody group and the isotype control group in the subcutaneous transplantation model. Therefore, the antibody accumulation within the tumor in vivo is based on the EPR effect. The liver metastasis generated by an intrasplenic injection of T-HCT 116 cells was clearly visualized by the NIR-conjugated anti-HLA probe but not by the orange-red fluorescent signal derived from the tdTomato reporter. This result demonstrated the superiority of the NIR probes over the tdTomato reporter protein at enhancing tissue penetration. In another xenograft model, patient-derived xenografts (PDX) of LC11-JCK (human non-small cell lung cancer) were successfully visualized using the NIR-conjugated macromolecule probe without any genetic modification. These results suggested that NIR-conjugated macromolecule, preferably, anti-HLA antibody probe is a valuable tool for the detection of human tumors in experimental metastasis models using whole-body imaging.
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非小细胞肺癌的患者衍生异种移植物：旧模型的复兴，用于研究定制治疗和癌症干细胞的现代概念。
影响因子：
--
作者：
Moro M;Bertolini G;Tortoreto M;Pastorino U;Sozzi G;Roz L
通讯作者：
Roz L
DOI：
10.1126/science.1168683
发表时间：
2009-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Shu X;Royant A;Lin MZ;Aguilera TA;Lev-Ram V;Steinbach PA;Tsien RY
通讯作者：
Tsien RY
影响因子：
8.4
作者：
Oshika, Y;Nakamura, M;Ueyama, Y
通讯作者：
Ueyama, Y
影响因子：
--
作者：
Lin MZ;McKeown MR;Ng HL;Aguilera TA;Shaner NC;Campbell RE;Adams SR;Gross LA;Ma W;Alber T;Tsien RY
通讯作者：
Tsien RY
DOI：
10.1016/j.bbrc.2011.01.042
发表时间：
2011-02-18
影响因子：
3.1
作者：
Hasegawa M;Kawai K;Mitsui T;Taniguchi K;Monnai M;Wakui M;Ito M;Suematsu M;Peltz G;Nakamura M;Suemizu H
通讯作者：
Suemizu H