2009-9-8 PNAS：利用发光蛋白发现活体动物体内肿瘤

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来源 EurekAlert! 2009-9-10 9:20:27 26
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PNAS：利用发光蛋白发现活体动物体内肿瘤) J1 Y" E& u% c5 d, ?/ m9 _5 C! R

2 t& M7 u+ O  H3 h: A  _科学家开发出了一种使用荧光成像技术探测活体动物癌症扩散的方法，这可能有助于提供一个比通常用于癌症成像的放射性物质更廉价和更少毒性的方法。为了帮助对抗癌症，许多制药公司已经开发出了能识别癌细胞表面表达的抗原的特异性抗体，从而发现其他方法无法发现的微小肿瘤。/ i! {8 N8 p7 P: c# g+ e' j4 d+ z
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Yoshihiro Ohmiya及其同事把这样一个抗体（ 一种在许多癌细胞表面表达的胚胎抗原） 与一种红色生物冷光蛋白结合起来。后者是他们把一种远红荧光染料与海萤的荧光素酶结合制造出来的。除了红色，大多数生物发光光谱出现在可见光范围，在这个范围中它们与血红素重叠，降低了生物发光的强度。这种红色冷光探针产生了一种能发现活体小鼠肝癌细胞的荧光。这组科学家说，由于存在商品化的抗癌抗体，这种方法可能迅速利用，用于让癌症可视化，并且提供对于许多类型的肿瘤的早期检测.
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  ^8 T/ l# [& B% {' y) T8 x原始出处：) C1 u3 l- |3 q% F: y3 i
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PNAS September 8, 2009, doi: 10.1073/pnas.0908594106
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In vivo far-red luminescence imaging of a biomarker based on BRET from Cypridina bioluminescence to an organic dye
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/ ?% V+ o! V6 XChun Wua, Kazuhiro Minob, Hidetoshi Akimotob, Makiko Kawabatac, Koji Nakamurac, Michitaka Ozakib and Yoshihiro Ohmiyaa,b,d,1
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aResearch Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology, 1-8-31 Midorigaoka, Ikeda 563-8577, Japan;& y- w  m, E. F, x6 [
bGraduate School of Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan;* O, S7 w5 a7 C* i; X. u
cLivTech, Inc, 907 Nogawa, Miyamae-ku, Kawasaki 216-0001, Japan; and
( |5 i! S" B, B' E0 vdResearch Institute for Genome-based Biofactory, National Institute of Advanced Industrial Science and Technology, 2-17-2-1 Tsukisamu-Higashi, Sapporo 062-8517, Japan
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. R5 l- J: m6 o, @9 D# g; Q- T0 ]We aimed to develop a far-red luminescence imaging technology for visualization of disease specific antigens on cell surfaces in a living body. First, we conjugated a far-red fluorescent indocyanine derivative to biotinylated Cypridina luciferase. This conjugate produced a bimodal spectrum that has long-wavelength bioluminescence emission in the far-red region as a result of bioluminescence resonance energy transfer. To generate a far-red luminescent probe with targeting and imaging capabilities of tumors, we then linked this conjugate to an anti-human Dlk-1 monoclonal antibody via the biotin-avidin interaction. This far-red luminescent probe enabled us to obtain high-resolution microscopic images of live, Dlk-1-expressing Huh-7 cells without an external light source, and to monitor the accumulation of this probe in tumor-bearing mice. Thus this far-red luminescent probe is a convenient analytical tool for the evaluations of monoclonal antibody localization in a living body.

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