Iridium complex probes for monitoring of cellular oxygen levels and imaging of hypoxic tissues

Toshitada Yoshihara; Atsushi Kobayashi; Shinpei Oda; Masahiro Hosaka; Toshiyuki Takeuchi; Seiji Tobita

doi:10.1117/12.910170

2 February 2012 Iridium complex probes for monitoring of cellular oxygen levels and imaging of hypoxic tissues

Toshitada Yoshihara, Atsushi Kobayashi, Shinpei Oda, Masahiro Hosaka, Toshiyuki Takeuchi, Seiji Tobita

Proceedings Volume 8233, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications IV; 82330A (2012) https://doi.org/10.1117/12.910170
Event: SPIE BiOS, 2012, San Francisco, California, United States

Abstract

We have recently reported that a red-emitting iridium complex (btp)₂ Ir (acac) (BTP) serves as a hypoxia-sensing probe for tumor imaging in living mice. BTP exhibits oxygen-sensitive phosphorescence that can be utilized to monitor oxygen levels in living cells and to visualize hypoxic tissues. To improve the tissue penetrance of BTP, we designed and synthesized near-IR emitting iridium complexes by two different approaches: extension of the π- conjugated system of benzothienyl-pyridinato ligand in BTP and introduction of substituents into suitable positions of ligands. The former approach was successful, and near-IR emitting iridium complexes were obtained without reduction in the emission quantum yield. Cellular uptake of BTP was greatly improved by introducing a hydrophilic group into the acetylacetonato ligand. Using these improved probes, in-vivo lifetime measurements were made to substantiate the hypoxia of tumor tissues in SCC-7 tumor-bearing mice. The second-harmonic (532 nm) of Nd³⁺:YAG laser was used to excite iridium complexes in tissues, and the phosphorescence lifetime was measured using the time-correlated single photon counting technique. The phosphorescence emitted from the tumor region actually gave longer lifetimes compared to those emitted from the normal tissues, demonstrating the hypoxic nature of tumor tissues.

Citation Download Citation

Toshitada Yoshihara, Atsushi Kobayashi, Shinpei Oda, Masahiro Hosaka, Toshiyuki Takeuchi, and Seiji Tobita "Iridium complex probes for monitoring of cellular oxygen levels and imaging of hypoxic tissues", Proc. SPIE 8233, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications IV, 82330A (2 February 2012); https://doi.org/10.1117/12.910170

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