PMID- 22687695
OWN - NLM
STAT- MEDLINE
DCOM- 20130312
LR  - 20190724
IS  - 1347-5231 (Electronic)
IS  - 0031-6903 (Linking)
VI  - 132
IP  - 5
DP  - 2012
TI  - [Development of a method of high-contrasted nuclear medical imaging of 
      hypoxia-inducible factor-1-active tumor by using a pretargeting approach].
PG  - 595-600
AB  - In solid tumors, hypoxic regions arise because of an imbalance between oxygen 
      supply and consumption. The transcription factor hypoxia-inducible factor-1 
      (HIF-1), which is overexpressed in hypoxic regions, was recently reported to be a 
      master transcriptional activator of various genes (such as those involved in 
      glucose metabolism, vascularization, invasion, and metastasis) related to 
      malignant phenotypes. Therefore, the development of techniques for the 
      noninvasive detection of HIF-1-active hypoxic tumor cells is of great interest. 
      Although various modalities are used for molecular imaging in vivo, nuclear 
      medical imaging, which can give information about organ functions, plays a 
      central quantitative role in molecular imaging. However, because radioactive 
      probes become attenuated due to the nuclide-specific half-life, an appropriate 
      probe design and/or imaging method is required to obtain a high-contrasted image 
      within a limited time. My colleagues and I have developed a probe and a method 
      for the rapid detection of HIF-1-active hypoxic regions in tumors. Because the alpha 
      subunit of HIF-1 (HIF-1alpha) controls the transcriptional activity of HIF-1 and is 
      unique in that its degradation is regulated by the oxygen partial pressure, we 
      first developed a fusion protein probe that is degraded similarly as HIF-1alpha. 
      Then, to control the biodistribution of radioactivity, we utilized a 
      "pretargeting method" that uses a combination of the fusion protein and a 
      small-molecule radioactive probe that can bind to the protein and is rapidly 
      cleared from the blood. Rapid and high-contrast imaging of HIF-1-active tumors 
      can be achieved with this pretargeting method.
FAU - Ueda, Masashi
AU  - Ueda M
AD  - Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of 
      Medicine, Kyoto University, Japan. uedama@kuhp.kyoto-u.ac.jp
LA  - jpn
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Japan
TA  - Yakugaku Zasshi
JT  - Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
JID - 0413613
RN  - 0 (Fluorine Radioisotopes)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (RNA-Binding Protein FUS)
RN  - 0 (Radiopharmaceuticals)
SB  - IM
MH  - Animals
MH  - Fluorine Radioisotopes
MH  - Humans
MH  - *Hypoxia-Inducible Factor 1/metabolism/physiology
MH  - Mice
MH  - Neoplasms/*diagnostic imaging/metabolism
MH  - Positron-Emission Tomography/*methods
MH  - RNA-Binding Protein FUS
MH  - Radiopharmaceuticals
MH  - Tomography, Emission-Computed, Single-Photon/*methods
EDAT- 2012/06/13 06:00
MHDA- 2013/03/13 06:00
CRDT- 2012/06/13 06:00
PHST- 2012/06/13 06:00 [entrez]
PHST- 2012/06/13 06:00 [pubmed]
PHST- 2013/03/13 06:00 [medline]
AID - JST.JSTAGE/yakushi/132.595 [pii]
AID - 10.1248/yakushi.132.595 [doi]
PST - ppublish
SO  - Yakugaku Zasshi. 2012;132(5):595-600. doi: 10.1248/yakushi.132.595.