Phosphorescent light-emitting iridium complexes serve as a hypoxia-sensing probe for tumor imaging in living animals

Toshiyuki Takeuchi; Shaojuan Zhang; Kazuya Negishi; Toshitada Yoshihara; Masahiro Hosaka; Seiji Tobita

doi:10.1117/12.855704

16 February 2010 Phosphorescent light-emitting iridium complexes serve as a hypoxia-sensing probe for tumor imaging in living animals

Toshiyuki Takeuchi, Shaojuan Zhang, Kazuya Negishi, Toshitada Yoshihara, Masahiro Hosaka, Seiji Tobita

Author Affiliations +

Proceedings Volume 7576, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II; 75760B (2010) https://doi.org/10.1117/12.855704
Event: SPIE BiOS, 2010, San Francisco, California, United States

Abstract

Iridium complex, a promising organic light-emitting diode material for next generation television and computer displays, emits phosphorescence. Phosphorescence is quenched by oxygen. We used this oxygen-quenching feature for imaging tumor hypoxia. Red light-emitting iridium complex Ir(btp)₂(acac) (BTP) presented hypoxia-dependent light emission in culture cell lines, whose intensity was in parallel with hypoxia-inducible factor (HIF)-1 expression. BTP was further applied to imaging five nude mouse-transplanted tumors. All tumors presented a bright BTP-emitting image as early as 5 min after the injection. The BTP-dependent tumor image peaked at 1 to 2 h after the injection, and was then removed from tumors within 24 h. The minimal BTP image recognition size was at least 2 mm in diameter. By morphological examination and phosphorescence lifetime measurement, BTP is presumed to localize to the tumor cells, not to stay in the tumor microvessels by binding to albumin. The primary problem on suse of luminescent probe for tumor imaging is its weak penetrance to deep tissues from the skin surface. Since BTP is easily modifiable, we made BTP analogues with a longer excitation/emission wavelength to improve the tissue penetrance. One of them, BTPHSA, displayed 560/720 wavelength, and depicted its clear imaging from tumors transplanted over 6-7 mm deep from the skin surface. We suggest that BTP analogues have a vast potential for imaging hypoxic lesions such as tumor tissues.

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Toshiyuki Takeuchi, Shaojuan Zhang, Kazuya Negishi, Toshitada Yoshihara, Masahiro Hosaka, and Seiji Tobita "Phosphorescent light-emitting iridium complexes serve as a hypoxia-sensing probe for tumor imaging in living animals", Proc. SPIE 7576, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II, 75760B (16 February 2010); https://doi.org/10.1117/12.855704

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