PMID- 23338175
OWN - NLM
STAT- MEDLINE
DCOM- 20130716
LR  - 20211021
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 42
IP  - 3
DP  - 2013 Mar
TI  - Biological characteristics of intratumoral [F-18]‑fluoromisonidazole distribution 
      in a rodent model of glioma.
PG  - 823-30
LID - 10.3892/ijo.2013.1781 [doi]
AB  - Accurate imaging to identify hypoxic regions in tumors is key for radiotherapy 
      planning. [F-18]‑fluoro-misonidazole ([F-18]-FMISO) is widely used for tumor 
      hypoxia imaging and has the potential to optimize radiotherapy planning. However, 
      the biological characteristics of intratumoral [F-18]-FMISO distribution have not 
      yet been fully investigated. In hypoxic cells, the hypoxia-inducible factor-1 
      (HIF-1) target proteins that induce cellular proliferation and glucose 
      metabolism, glucose transporter-1 (Glut-1) and hexokinase-II (HK-II), are 
      upregulated. In this study, we determined the intratumoral distribution of 
      [F-18]-FMISO by autoradiography (ARG) and compared it with pimonidazole uptake, 
      expression of Glut-1, tumor proliferative activity (Ki-67 index) and glucose 
      metabolism ([C-14]2-fluoro-2-deoxy-D-glucose uptake; [C-14]-FDG) in a glioma rat 
      model. Five C6 glioma‑bearing rats were injected with [F-18]-FMISO and 
      [C-14]-FDG. After 90 min, the rats were injected with pimonidazole and 60 min 
      later, the rats were sacrificed and tumor tissues were sectioned into slices. The 
      adjacent slices were used for ARG and immunohistochemical (IHC) analyses of 
      pimonidazole, Glut-1 and Ki-67. [F-18]-FMISO ARG images were divided into regions 
      of high [F-18]-FMISO uptake (FMISO+) and low [F-18]-FMISO uptake (FMISO-). 
      Pimonidazole and Glut-1 expression levels, Ki-67 index and [C-14]-FDG 
      distribution were evaluated in the regions of interest (ROIs) placed on FMISO+ 
      and FMISO-. [F-18]-FMISO distribution was generally consistent with pimonidazole 
      distribution. The percentage of positively stained areas (% positive) of Glut-1 
      in FMISO+ was significantly higher compared to FMISO- (24 +/- 8% in FMISO+ and 9 +/- 
      4% in FMISO-; P<0.05). There were no significant differences in Ki-67 index and 
      [C-14]-FDG uptake between FMISO+ and FMISO- (for Ki-67, 10 +/- 5% in FMISO+ and 12 
      +/- 5% in FMISO-, P=ns; for [C-14]-FDG, 1.4 +/- 0.3% ID/g/kg in FMISO+ and 1.3 +/- 0.3% 
      ID/g/kg in FMISO-, P = ns). Intratumoral [F-18]-FMISO distribution reflected 
      tumor hypoxia and expression of the hypoxia‑related gene product Glut-1; it did 
      not, however, reflect tumor proliferation or glucose metabolism. Our findings 
      help elucidate the biological characteristics of intratumoral [F-18]-FMISO 
      distribution that are relevant to radiotherapy planning.
FAU - Hatano, Toshiyuki
AU  - Hatano T
AD  - Central Institute of Isotope Science, Hokkaido University, Sapporo, Japan.
FAU - Zhao, Songji
AU  - Zhao S
FAU - Zhao, Yan
AU  - Zhao Y
FAU - Nishijima, Ken-Ichi
AU  - Nishijima K
FAU - Kuno, Norihito
AU  - Kuno N
FAU - Hanzawa, Hiroko
AU  - Hanzawa H
FAU - Sakamoto, Takeshi
AU  - Sakamoto T
FAU - Tamaki, Nagara
AU  - Tamaki N
FAU - Kuge, Yuji
AU  - Kuge Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130118
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Nitroimidazoles)
RN  - 082285VIDF (fluoromisonidazole)
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - 46JO4D76R2 (pimonidazole)
RN  - 8FE7LTN8XE (Misonidazole)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Autoradiography
MH  - Biological Transport
MH  - Brain Neoplasms/*diagnosis
MH  - Cell Hypoxia
MH  - Cell Proliferation
MH  - Fluorodeoxyglucose F18/metabolism
MH  - Glioma/*diagnosis
MH  - Glucose/metabolism
MH  - Glucose Transporter Type 1/biosynthesis
MH  - Hexokinase/biosynthesis
MH  - Hypoxia-Inducible Factor 1/genetics/metabolism
MH  - Ki-67 Antigen
MH  - Male
MH  - Misonidazole/*analogs & derivatives/metabolism
MH  - Nitroimidazoles/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Tissue Distribution
PMC - PMC3597456
EDAT- 2013/01/23 06:00
MHDA- 2013/07/17 06:00
PMCR- 2013/01/18
CRDT- 2013/01/23 06:00
PHST- 2012/11/09 00:00 [received]
PHST- 2012/12/18 00:00 [accepted]
PHST- 2013/01/23 06:00 [entrez]
PHST- 2013/01/23 06:00 [pubmed]
PHST- 2013/07/17 06:00 [medline]
PHST- 2013/01/18 00:00 [pmc-release]
AID - ijo-42-03-0823 [pii]
AID - 10.3892/ijo.2013.1781 [doi]
PST - ppublish
SO  - Int J Oncol. 2013 Mar;42(3):823-30. doi: 10.3892/ijo.2013.1781. Epub 2013 Jan 18.