PMID- 21824221
OWN - NLM
STAT- MEDLINE
DCOM- 20111219
LR  - 20191210
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Linking)
VI  - 102
IP  - 11
DP  - 2011 Nov
TI  - Evaluation of [125I]IPOS as a molecular imaging probe for hypoxia-inducible 
      factor-1-active regions in a tumor: comparison among single-photon emission 
      computed tomography/X-ray computed tomography imaging, autoradiography, and 
      immunohistochemistry.
PG  - 2090-6
LID - 10.1111/j.1349-7006.2011.02057.x [doi]
AB  - To image hypoxia-inducible factor-1 (HIF-1)-active tumors, we previously 
      developed a chimeric protein probe ([(123/125) I]IPOS) that is degraded in the 
      same manner as HIF-1alpha under normoxic conditions. In the present study, we aim to 
      show that the accumulation of radioiodinated POS reflects the expression of 
      HIF-1. In vivo single-photon emission computed tomography (SPECT)/X-ray CT (CT) 
      imaging, autoradiography, and double-fluorescent immunostaining for HIF-1alpha and 
      pimonidazole (PIMO) were carried out 24 h after the injection of [(125) I]IPOS. 
      Tumor metabolite analysis was also carried out. A tumor was clearly visualized by 
      multi-pinhole, high-resolution SPECT/CT imaging with [(125) I]IPOS. The obtained 
      images were in accordance with the corresponding autoradiograms and with the 
      results of ex vivo biodistribution. A metabolite analysis revealed that 77% of 
      the radioactivity was eluted in the macromolecular fraction, suggesting that the 
      radioactivity mainly existed as [(125) I]IPOS in the tumors. Immunohistochemistry 
      revealed that the HIF-1alpha-positive areas and PIMO-positive areas were not always 
      identical, only some of the regions were positive for both markers. The areas 
      showing [(125) I]IPOS accumulation were positively and significantly correlated 
      with the HIF-1alpha-positive areas (R = 0.75, P < 0.0001). The correlation 
      coefficient between [(125) I]IPOS-accumulated areas and HIF-1alpha-positive areas was 
      significantly greater than that between the [(125) I]IPOS-accumulated areas and 
      the PIMO-positive areas (P < 0.01). These findings indicate that [(125) I]IPOS 
      accumulation reflects HIF-1 expression. Thus, [(123/125) I]IPOS can serve as a 
      useful probe for the molecular imaging of HIF-1-active tumors.
CI  - (c) 2011 Japanese Cancer Association.
FAU - Ueda, Masashi
AU  - Ueda M
AD  - Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of 
      Medicine, Kyoto University, Kyoto, Japan.
FAU - Kudo, Takashi
AU  - Kudo T
FAU - Mutou, Yasuko
AU  - Mutou Y
FAU - Umeda, Izumi Ogihara
AU  - Umeda IO
FAU - Miyano, Azusa
AU  - Miyano A
FAU - Ogawa, Kei
AU  - Ogawa K
FAU - Ono, Masahiro
AU  - Ono M
FAU - Fujii, Hirofumi
AU  - Fujii H
FAU - Kizaka-Kondoh, Shinae
AU  - Kizaka-Kondoh S
FAU - Hiraoka, Masahiro
AU  - Hiraoka M
FAU - Saji, Hideo
AU  - Saji H
LA  - eng
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110915
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (3-(iodobenzoyl)norbiotinamide-PTD-ODD-SAV fusion protein)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nitroimidazoles)
RN  - 0 (Radiopharmaceuticals)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 46JO4D76R2 (pimonidazole)
RN  - 6SO6U10H04 (Biotin)
SB  - IM
MH  - Animals
MH  - *Autoradiography
MH  - Biotin/*analogs & derivatives/pharmacokinetics
MH  - Female
MH  - *Fluorescent Antibody Technique, Direct
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*analysis
MH  - *Iodine Radioisotopes/pharmacokinetics
MH  - Mammary Neoplasms, Experimental/*diagnostic imaging/metabolism
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Neoplasm Proteins/*analysis
MH  - Nitroimidazoles/analysis
MH  - *Radiopharmaceuticals/pharmacokinetics
MH  - *Recombinant Fusion Proteins/pharmacokinetics
MH  - Tissue Distribution
MH  - Tomography, Emission-Computed, Single-Photon/*methods
MH  - *Tomography, X-Ray Computed
EDAT- 2011/08/10 06:00
MHDA- 2011/12/20 06:00
CRDT- 2011/08/10 06:00
PHST- 2011/08/10 06:00 [entrez]
PHST- 2011/08/10 06:00 [pubmed]
PHST- 2011/12/20 06:00 [medline]
AID - 10.1111/j.1349-7006.2011.02057.x [doi]
PST - ppublish
SO  - Cancer Sci. 2011 Nov;102(11):2090-6. doi: 10.1111/j.1349-7006.2011.02057.x. Epub 
      2011 Sep 15.