A luciferin analogue generating near-infrared bioluminescence achieves highly sensitive deep-tissue imaging.
A luciferin analogue generating near-infrared bioluminescence achieves highly sensitive deep-tissue imaging.
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DOI：
10.1038/ncomms11856
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发表时间：
2016-06-14
影响因子：
16.6
通讯作者：
Kizaka-Kondoh S
中科院分区：
文献类型：
--
作者：
Kuchimaru T;Iwano S;Kiyama M;Mitsumata S;Kadonosono T;Niwa H;Maki S;Kizaka-Kondoh S
在临床前癌症研究中，使用萤火虫荧光素酶和 D-荧光素进行生物发光成像已成为监测体外和体内生物过程的标准。然而，D-荧光素产生的生物发光的发射最大值 (λmax) 为 562 nm，光在生物组织中的穿透性不高。这强调需要开发红移生物发光成像系统以提高深层组织中目标的检测灵敏度。在这里，我们表征了新合成的荧光素类似物 AkaLumine-HCl 的生物发光特性。 AkaLumine-HCl 与天然萤火虫荧光素酶反应时产生的生物发光处于近红外波长范围（λmax=677nm），与 D-荧光素和新兴的合成荧光素 CycLuc1 相比，在极低浓度下获得最大信号，从而显着提高深层组织的目标检测灵敏度。这些特性为在各种动物模型中使用天然萤火虫荧光素酶进行非侵入性生物发光成像提供了更灵敏和准确的方法。 D-荧光素是体外和体内成像的标准生物发光底物。作者在这里介绍了 AkaLumine-HCl，这是一种可溶性荧光素类似物，具有近红外发射最大值，与 D-荧光素相比，它可以在较低浓度下进行深部组织成像。
In preclinical cancer research, bioluminescence imaging with firefly luciferase and D-luciferin has become a standard to monitor biological processes both in vitro and in vivo. However, the emission maximum (λmax) of bioluminescence produced by D-luciferin is 562 nm where light is not highly penetrable in biological tissues. This emphasizes a need for developing a red-shifted bioluminescence imaging system to improve detection sensitivity of targets in deep tissue. Here we characterize the bioluminescent properties of the newly synthesized luciferin analogue, AkaLumine-HCl. The bioluminescence produced by AkaLumine-HCl in reactions with native firefly luciferase is in the near-infrared wavelength ranges (λmax=677 nm), and yields significantly increased target-detection sensitivity from deep tissues with maximal signals attained at very low concentrations, as compared with D-luciferin and emerging synthetic luciferin CycLuc1. These characteristics offer a more sensitive and accurate method for non-invasive bioluminescence imaging with native firefly luciferase in various animal models. D-luciferin is the standard bioluminescent substrate for in vitro and in vivo imaging. Here the authors introduce AkaLumine-HCl, a soluble luciferin analogue with a near-infrared emission maximum, which allows deep tissue imaging at lower concentrations than D-luciferin.