Abstract

Bioluminescence imaging (BLI) is useful to monitor cell movement and gene expression in live animals. However, D-luciferin has a short wavelength (560 nm) which is absorbed by tissues and the use of near-infrared (NIR) luciferin analogues enable high sensitivity in vivo BLI. The AkaLumine-AkaLuc BLI system (Aka-BLI) can detect resolution at the single-cell level; however, it has a clear hepatic background signal. Here, to enable the highly sensitive detection of bioluminescence from the surrounding liver tissues, we focused on seMpai (C15H16N3O2S) which has been synthesized as a luciferin analogue and has high luminescent abilities as same as AkaLumine. We demonstrated that seMpai BLI could detect micro-signals near the liver without any background signal. The solution of seMpai was neutral; therefore, seMpai imaging did not cause any adverse effect in mice. seMpai enabled a highly sensitive in vivo BLI as compared to previous techniques. Our findings suggest that the development of a novel mutated luciferase against seMpai may enable a highly sensitive BLI at the single-cell level without any background signal. Novel seMpai BLI system can be used for in vivo imaging in the fields of life sciences and medicine.

Highlights

  • Bioluminescence imaging (BLI) is used to monitor the behavior of cells and molecules in animal studies [1,2]

  • The in vivo BLI system with luciferase is used for the quantification of tumor volume, monitoring gene expression and detection of cancer metastasis [3,4,5,6,7,8]

  • To improve the background signal in NIR BLI, we focused on a luciferin analogue seMpai (C15H16N3O2S), which demonstrates a high level of luminescence similar to that of AkaLumine and TokeOni [17]

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Summary

Introduction

Bioluminescence imaging (BLI) is used to monitor the behavior of cells and molecules in animal studies [1,2]. The in vivo BLI system with luciferase is used for the quantification of tumor volume, monitoring gene expression and detection of cancer metastasis [3,4,5,6,7,8]. High sensitivity in vivo BLI in deep tissues is difficult by absorption of short wavelength bioluminescence. Recent studies showed that luciferase-luciferin analogue reactions at near-infrared (NIR) wavelengths enable a highly sensitive in vivo BLI [9,10]. The AkaLumine-AkaLuc bioluminescence imaging system (Aka-BLI) at NIR wavelengths can detect resolution at the single-cell level in several live animals [11]. NIR imaging techniques using luciferin analogues are used in oncology, neuroscience and ethology [2,12,13,14]

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