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Molecular Imaging and Biology

, Volume 13, Issue 5, pp 1003–1010 | Cite as

PET Imaging of Hypoxia-Inducible Factor-1-Active Tumor Cells with Pretargeted Oxygen-Dependent Degradable Streptavidin and a Novel 18F-Labeled Biotin Derivative

  • Takashi Kudo
  • Masashi Ueda
  • Hiroaki Konishi
  • Hidekazu Kawashima
  • Yuji Kuge
  • Takahiro Mukai
  • Azusa Miyano
  • Shotaro Tanaka
  • Shinae Kizaka-Kondoh
  • Masahiro Hiraoka
  • Hideo SajiEmail author
Research Article

Abstract

Purpose

We aimed to evaluate the feasibility of using streptavidin–biotin-based pretargeting for positron emission tomography (PET) imaging of hypoxia-inducible factor (HIF)-1-active tumors.

Procedures

We used POS, a genetically engineered form of streptavidin that selectively stabilizes in HIF-1-active cells, and (4-18F-fluorobenzoyl)norbiotinamide (18F-FBB), a radiolabeled biotin derivative, for performing a biodistribution study and for PET imaging. The tumoral 18F-FBB accumulation was compared to the HIF-1-dependent luciferase bioluminescence and HIF-1α immunohistochemical signal.

Results

18F-FBB accumulation was observed in POS-pretargeted tumors in mice (2.85 ± 0.55% injected dose per gram at 3 h), and clear PET images were obtained at the same time point. The tumoral 18F-FBB accumulation positively correlated with luciferase bioluminescence (R = 0.72, P < 0.05), and most of the area showing 18F-FBB accumulation corresponded to HIF-1α-positive areas.

Conclusion

Pretargeting with POS and 18F-FBB is an effective approach for PET imaging of HIF-1-active areas in tumors.

Key Words

Tumor hypoxia Hypoxia-inducible factor-1 (HIF-1) Oxygen-dependent degradation domain (ODD) Pretargeting 18F-labeled biotin derivative 

Notes

Acknowledgments

We are grateful to Hiroyuki Kimura, Kenji Tomatsu, and Yu Ogawa for preparation of 18F-SFB, and Kei Ogawa for skilled technical assistance.

This study was supported in part by Health Labour Sciences Research Grant for Research on Advanced Medical Technology from the Ministry of Health, Labour and Welfare of Japan; “R&D of Molecular Imaging Equipment for Malignant Tumor Therapy Support” by the New Energy and Industrial Technology Development Organization (NEDO), 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.

Conflict of interest

The authors have no conflict of interest.

Supplementary material

11307_2010_418_MOESM1_ESM.pdf (33 kb)
ESM 1 (PDF 32.5 kb)

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Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2010

Authors and Affiliations

  • Takashi Kudo
    • 1
  • Masashi Ueda
    • 1
    • 2
  • Hiroaki Konishi
    • 1
  • Hidekazu Kawashima
    • 1
    • 3
  • Yuji Kuge
    • 1
    • 4
  • Takahiro Mukai
    • 5
  • Azusa Miyano
    • 1
  • Shotaro Tanaka
    • 6
  • Shinae Kizaka-Kondoh
    • 6
  • Masahiro Hiraoka
    • 6
  • Hideo Saji
    • 1
    Email author
  1. 1.Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto UniversityKyotoJapan
  2. 2.Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of MedicineKyoto UniversityKyotoJapan
  3. 3.Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of MedicineKyoto UniversityKyotoJapan
  4. 4.Central Institute of Isotope ScienceHokkaido UniversitySapporoJapan
  5. 5.Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical SciencesKyushu UniversityFukuokaJapan
  6. 6.Department of Radiation Oncology and Image-Applied Therapy, Graduate School of MedicineKyoto UniversityKyotoJapan

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