Development of an oxygen-sensitive degradable peptide probe for the imaging of hypoxia-inducible factor-1-active regions in tumors

Masashi Ueda, Kei Ogawa, Azusa Miyano, Masahiro Ono, Shinae Kizaka-Kondoh, Hideo Saji

Research output: Contribution to journalArticle

9 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)713-721
Number of pages9
JournalMolecular Imaging and Biology
Issue number6
Publication statusPublished - Dec 2013
Externally publishedYes



  • Hypoxia-inducible factor-1
  • Nuclear medical imaging
  • Oxygen-dependent degradation
  • Peptide
  • Tumor hypoxia

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Radiology Nuclear Medicine and imaging

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