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Rapid detection of hypoxia-inducible factor-1-active tumours: pretargeted imaging with a protein degrading in a mechanism similar to hypoxia-inducible factor-1α

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Abstract

Purpose

Hypoxia-inducible factor-1 (HIF-1) plays an important role in malignant tumour progression. For the imaging of HIF-1-active tumours, we previously developed a protein, POS, which is effectively delivered to and selectively stabilized in HIF-1-active cells, and a radioiodinated biotin derivative, (3-123I-iodobenzoyl)norbiotinamide (123I-IBB), which can bind to the streptavidin moiety of POS. In this study, we aimed to investigate the feasibility of the pretargeting method using POS and 123I-IBB for rapid imaging of HIF-1-active tumours.

Methods

Tumour-implanted mice were pretargeted with POS. After 24 h, 125I-IBB was administered and subsequently, the biodistribution of radioactivity was investigated at several time points. In vivo planar imaging, comparison between 125I-IBB accumulation and HIF-1 transcriptional activity, and autoradiography were performed at 6 h after the administration of 125I-IBB. The same sections that were used in autoradiographic analysis were subjected to HIF-1α immunohistochemistry.

Results

125I-IBB accumulation was observed in tumours of mice pretargeted with POS (1.6%ID/g at 6 h). This result is comparable to the data derived from 125I-IBB-conjugated POS-treated mice (1.4%ID/g at 24 h). In vivo planar imaging provided clear tumour images. The tumoral accumulation of 125I-IBB significantly correlated with HIF-1-dependent luciferase bioluminescence (R=0.84, p<0.01). The intratumoral distribution of 125I-IBB was heterogeneous and was significantly correlated with HIF-1α-positive regions (R=0.58, p<0.0001).

Conclusion

POS pretargeting with 123I-IBB is a useful technique in the rapid imaging and detection of HIF-1-active regions in tumours.

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Acknowledgments

The authors would like to thank Nihon Medi-Physics for providing ammonium 123I-iodide. This work was supported in part by “R&D of Molecular Imaging Equipment for Malignant Tumor Therapy Support” of the New Energy and Industrial Technology Development Organization (NEDO), Japan, a Health Labour Sciences Research Grant for Research on Advanced Medical Technology from the Ministry of Health, Labour and Welfare of Japan, and a Grant-in-Aid for Exploratory Research (17659010) and a Grant-in-Aid for Young Scientists (B) (21791187) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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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, Takashi Kudo, Yuji Kuge, Hiroaki Konishi, Azusa Miyano, Masahiro Ono & Hideo Saji

  3. Central Institute of Isotope Science, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-0815, Japan

    Yuji Kuge

  4. Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Takahiro Mukai

  5. Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Shotaro Tanaka, Shinae Kizaka-Kondoh & Masahiro Hiraoka

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  1. Masashi Ueda
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Correspondence to Hideo Saji.

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Ueda, M., Kudo, T., Kuge, Y. et al. Rapid detection of hypoxia-inducible factor-1-active tumours: pretargeted imaging with a protein degrading in a mechanism similar to hypoxia-inducible factor-1α. Eur J Nucl Med Mol Imaging 37, 1566–1574 (2010). https://doi.org/10.1007/s00259-010-1467-4

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  • DOI: https://doi.org/10.1007/s00259-010-1467-4

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