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Development of an Oxygen-Sensitive Degradable Peptide Probe for the Imaging of Hypoxia-Inducible Factor-1-Active Regions in Tumors

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Abstract

Purpose

We aimed to develop a radiolabeled peptide probe for the imaging of hypoxia-inducible factor-1 (HIF-1)-active tumors.

Procedures

We synthesized the peptide probes that contain or lack an essential sequence of the oxygen-dependent degradation of HIF-1α in proteasomes (123/125I-DKOP30 or 125I-mDKOP, respectively). The degradation of probes was evaluated in vitro using cell lysates containing proteasomes. In vivo biodistribution study, planar imaging, autoradiography, and comparison between probe accumulation and HIF-1 transcriptional activity were also performed.

Results

The 125I-DKOP30 underwent degradation in a proteasome-dependent manner, while 125I-mDKOP was not degraded. Biodistribution analysis showed 125I-DKOP30 accumulation in tumors. The tumors were clearly visualized by in vivo imaging, and intratumoral distribution of 125I-DKOP30 coincided with the HIF-1α-positive hypoxic regions. Tumoral accumulation of 125I-DKOP30 was significantly correlated with HIF-1-dependent luciferase bioluminescence, while that of 125I-mDKOP was not.

Conclusion

123I-DKOP30 is a useful peptide probe for the imaging of HIF-1-active tumors.

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Acknowledgments

The authors would like to thank Nihon Medi-Physics Co. Ltd. for providing ammonium [123I]iodide. This work was supported in part by the Research and Development Project on Molecular Probes for Detection of Biological Features on Cancer of the New Energy and Industrial Technology Development Organization (NEDO), Japan, and a Grant-in-Aid for Young Scientists (B) (KAKENHI Grant Number 23791412) from the Japan Society for the Promotion of Science.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Masashi Ueda

  2. Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan

    Masashi Ueda, Kei Ogawa, Azusa Miyano, Masahiro Ono & Hideo Saji

  3. Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8503, Japan

    Shinae Kizaka-Kondoh

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  1. Masashi Ueda
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  2. Kei Ogawa
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  3. Azusa Miyano
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  4. Masahiro Ono
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  5. Shinae Kizaka-Kondoh
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  6. Hideo Saji
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Corresponding author

Correspondence to Hideo Saji.

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Ueda, M., Ogawa, K., Miyano, A. et al. Development of an Oxygen-Sensitive Degradable Peptide Probe for the Imaging of Hypoxia-Inducible Factor-1-Active Regions in Tumors. Mol Imaging Biol 15, 713–721 (2013). https://doi.org/10.1007/s11307-013-0647-6

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  • DOI: https://doi.org/10.1007/s11307-013-0647-6

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