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

• 上田, 真史

• Ogawa, Kei

• Miyano, Azusa

• Ono, Masahiro

• Kizaka-Kondoh, Shinae

• 佐治, 英郎

抄録

[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 ([123/125]I-DKOP30 or [125]I-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 [125]I-DKOP30 underwent degradation in a proteasome-dependent manner, while [125]I-mDKOP was not degraded. Biodistribution analysis showed [125]I-DKOP30 accumulation in tumors. The tumors were clearly visualized by in vivo imaging, and intratumoral distribution of [125]I-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 [125]I-mDKOP was not. [Conclusion] [123]I-DKOP30 is a useful peptide probe for the imaging of HIF-1-active tumors.

収録刊行物

• Molecular imaging and biology

  Molecular imaging and biology 15 (6), 713-721, 2013-05-21

  Springer

キーワード

• Tumor hypoxia
• Hypoxia-inducible factor-1
• Oxygen-dependent degradation
• Peptide
• Nuclear medical imaging
• Amino Acid Sequence
• Animals
• Autoradiography
• Cell Hypoxia
• Cell Line, Tumor
• Female
• HeLa Cells
• Humans
• Hypoxia-Inducible Factor 1/analysis
• Hypoxia-Inducible Factor 1/chemistry
• Hypoxia-Inducible Factor 1/metabolism
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C3H
• Mice, Nude
• Molecular Probe Techniques
• Molecular Probes/chemistry
• Molecular Probes/pharmacokinetics
• Molecular Sequence Data
• Peptides/chemistry
• Peptides/pharmacokinetics
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon

詳細情報

• CRID: 1050001335810692480
• NII論文ID: 120005587812
• NII書誌ID: AA1170000X
• ISSN: 15361632
• ISSN: 18602002
• HANDLE: 2433/196858
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles