A luciferin analogue generating near-infrared bioluminescence achieves highly sensitive deep-tissue imaging.
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.
School of Life Science and Technology, Tokyo Institute of Technology, 4259, Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
Takahiro
0000-0002-5355-3165
T
Kuchimaru
Graduate School of Informatics and Engineering, The University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan.
Satoshi
S
Iwano
Graduate School of Informatics and Engineering, The University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan.
Masahiro
M
Kiyama
School of Life Science and Technology, Tokyo Institute of Technology, 4259, Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
Shun
S
Mitsumata
School of Life Science and Technology, Tokyo Institute of Technology, 4259, Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
Tetsuya
T
Kadonosono
Graduate School of Informatics and Engineering, The University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan.
Haruki
H
Niwa
Graduate School of Informatics and Engineering, The University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, Tokyo 182-8585, Japan.
Shojiro
S
Maki
School of Life Science and Technology, Tokyo Institute of Technology, 4259, Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
Shinae
0000-0003-3085-5782
S
Kizaka-Kondoh
D000818:Animals; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D049454:Firefly Luciferin / Q000031:analogs & derivatives / Q000378:metabolism*; D006801:Humans; D049409:Luciferases, Firefly / Q000737:chemistry / Q000378:metabolism*; D008163:Luminescent Measurements / Q000295:instrumentation / Q000379:methods*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
C485197:luciferase, Photinus; D049454:Firefly Luciferin; D049409:Luciferases, Firefly