title: Development of an oxygen-sensitive degradable peptide probe for the imaging of hypoxia-inducible factor-1-active regions in tumors.
abstract: OBJECTIVE
  We aimed to develop a radiolabeled peptide probe for the imaging of hypoxia-inducible factor-1 (HIF-1)-active tumors.
  
  
  METHODS
  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 (125)I-DKOP30 was significantly correlated with HIF-1-dependent luciferase bioluminescence, while that of (125)I-mDKOP was not.
  
  
  CONCLUSIONS
  (123)I-DKOP30 is a useful peptide probe for the imaging of HIF-1-active tumors.
authors.affiliation: Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ueda
authors.forename: Kei
authors.initials: K
authors.lastname: Ogawa
authors.forename: Azusa
authors.initials: A
authors.lastname: Miyano
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.forename: Shinae
authors.initials: S
authors.lastname: Kizaka-Kondoh
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D015336:Molecular Probe Techniques; D015335:Molecular Probes / Q000737:chemistry / Q000493:pharmacokinetics*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D051793:Hypoxia-Inducible Factor 1; D015335:Molecular Probes; D010455:Peptides