PMID- 26963468
OWN - NLM
STAT- MEDLINE
DCOM- 20170224
LR  - 20170817
IS  - 1473-5628 (Electronic)
IS  - 0143-3636 (Linking)
VI  - 37
IP  - 7
DP  - 2016 Jul
TI  - Radiosensitizing effect of irisquinone on glioma through the downregulation of 
      HIF-1alpha evaluated by 18F-FDG and 18F-FMISO PET/CT.
PG  - 705-14
LID - 10.1097/MNM.0000000000000498 [doi]
AB  - OBJECTIVE: The aim of this study was to elucidate the radiosensitizing mechanism 
      of irisquinone (IQ) and evaluate the utility of F-fluorodeoxyglucose (F-FDG) and 
      F-fluoromisonidazole (F-FMISO) PET/computed tomography (CT) in assessing the 
      radiosensitizing effect of IQ. MATERIALS AND METHODS: In an in-vitro experiment, 
      C6 rat glioma cells were treated with IQ, radiation, or both. The viability and 
      radiosensitivity of C6 cells were detected using the MTT assay and clonogenic 
      survival assay. The expression of hypoxia-inducible factor-1alpha (HIF-1alpha) was 
      evaluated by real-time PCR and western blot. In an in-vivo experiment, C6 rat 
      glioma cells were implanted into the right flank of rats and treated with IQ, 
      radiation, both, or no treatment. F-FDG and F-FMISO PET/CT images were obtained 
      before and after treatment. The expression of HIF-1alpha was detected by 
      immunohistochemistry staining. RESULTS: In the in-vitro experiment, the results 
      of the MTT assay showed that the half-inhibition concentration (IC50) of IQ for 
      normoxic and hypoxic C6 tumor cells was 17.2 and 21.0 nmol/l, respectively. 
      Clonogenic survival assay showed that IQ could improve the radiosensitivity of 
      both normoxic and hypoxic C6 tumor cells. When the concentration of irradiation 
      was 20% IC50 (4.2 nmol/l), the sensitive enhancement ratio of normoxic and 
      hypoxic C6 tumor cells was 1.18 and 1.33, respectively. The mRNA and protein 
      expression levels of HIF-1alpha decreased significantly when treated with IQ plus 
      radiation compared with the other groups.In the in-vivo experiment, 24 or 48 h 
      after different treatments, the maximum standardized uptake values (SUVmax) of 
      F-FDG or F-FMISO uptake decreased in the radiation group and the IQ plus 
      radiation group, whereas these values increased in the control and IQ groups. The 
      SUVmax of F-FDG or F-FMISO uptake in IQ plus radiation group were lower than 
      those of the radiation group (t=3.28, 2.62, P<0.05). However, there was no 
      significant decrease in tumor volumes in the radiation group and the IQ plus 
      radiation treatment group early after treatment.Immunohistochemistry staining 
      showed that there were significant differences in the expression of HIF-1alpha in the 
      four groups (F=87.1, P<0.01). The SUVmax of both F-FDG and F-FMISO uptake showed 
      a significant correlation with the expression of HIF-1alpha. F-FMISO provided a 
      higher correlation coefficient with HIF-1alpha than F-FDG (r=0.93, 0.82, P<0.01). 
      CONCLUSION: The present experiments indicated that IQ enhanced the 
      radiosensitivity of C6 rat glioma cells both in vitro and in vivo. The primary 
      mechanism of this radiosensitizing effect involves the downregulation of HIF-1alpha. 
      F-FDG and F-FMISO PET/CT were sensitive and noninvasive for monitoring the early 
      radiosensitizing effect of IQ. Meanwhile, F-FMISO PET/CT provided more 
      information on the changes in tumor hypoxic status.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Nuclear Medicine, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
FAU - Zhang, Yu
AU  - Zhang Y
FAU - Yu, Wenjing
AU  - Yu W
FAU - Zhao, Xuefeng
AU  - Zhao X
FAU - Xue, Yangyang
AU  - Xue Y
FAU - Xu, Huiqin
AU  - Xu H
LA  - eng
PT  - Journal Article
PL  - England
TA  - Nucl Med Commun
JT  - Nuclear medicine communications
JID - 8201017
RN  - 0 (Benzoquinones)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Radiation-Sensitizing Agents)
RN  - 0 (Radiopharmaceuticals)
RN  - 082285VIDF (fluoromisonidazole)
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - 8FE7LTN8XE (Misonidazole)
RN  - GW0P1VS52W (irisquinone)
SB  - IM
MH  - Animals
MH  - Benzoquinones/*administration & dosage
MH  - Cell Line, Tumor
MH  - Down-Regulation/drug effects
MH  - Fluorodeoxyglucose F18/pharmacokinetics
MH  - Glioma/diagnostic imaging/*metabolism/*radiotherapy
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Male
MH  - Misonidazole/*analogs & derivatives/pharmacokinetics
MH  - Positron Emission Tomography Computed Tomography/methods
MH  - Radiation-Sensitizing Agents/administration & dosage
MH  - Radiopharmaceuticals
MH  - Radiotherapy Dosage
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Treatment Outcome
MH  - Tumor Hypoxia/drug effects/*radiation effects
EDAT- 2016/03/11 06:00
MHDA- 2017/02/25 06:00
CRDT- 2016/03/11 06:00
PHST- 2016/03/11 06:00 [entrez]
PHST- 2016/03/11 06:00 [pubmed]
PHST- 2017/02/25 06:00 [medline]
AID - 10.1097/MNM.0000000000000498 [doi]
PST - ppublish
SO  - Nucl Med Commun. 2016 Jul;37(7):705-14. doi: 10.1097/MNM.0000000000000498.