PMID- 23861829
OWN - NLM
STAT- MEDLINE
DCOM- 20140203
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 7
DP  - 2013
TI  - Early assessment of the efficacy of temozolomide chemotherapy in experimental 
      glioblastoma using [18F]FLT-PET imaging.
PG  - e67911
LID - 10.1371/journal.pone.0067911 [doi]
LID - e67911
AB  - Addition of temozolomide (TMZ) to radiation therapy is the standard treatment for 
      patients with glioblastoma (GBM). However, there is uncertainty regarding the 
      effectiveness of TMZ. Considering the rapid evolution of the disease, methods to 
      assess TMZ efficacy early during treatment would be of great benefit. Our aim was 
      to monitor early effects of TMZ in a mouse model of GBM using positron emission 
      tomography (PET) with 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT). METHODS: 
      Human glioma cells sensitive to TMZ (Gli36dEGFR-1) were treated with sub-lethal 
      doses of TMZ to obtain cells with lower sensitivity to TMZ (Gli36dEGFR-2), as 
      measured by growth and clonogenic assays. Gli36dEGFR-1 and Gli36dEGFR-2 cells 
      were subcutaneously (s.c.) or intracranially (i.c.) xenografted into nude mice. 
      Mice were treated for 7 days with daily injection of 25 or 50 mg/kg TMZ. 
      Treatment efficacy was measured using [(18)F]FLT-PET before treatment and after 2 
      days. Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) were used to 
      determine tumor volumes before treatment and after 7 days. RESULTS: A significant 
      difference was observed between TMZ and DMSO treated tumors in terms of 
      variations of [(18)F]FLT T/B ratio as soon as day 2 in the i.c. as well as in the 
      s.c. mouse model. Variations of [(18)F]FLT T/B uptake ratio between days 0 and 2 
      correlated with variations of tumor size between days 0 and 7 (s.c. model: 
      n(tumor) = 17 in n(mice) = 11, P<0.01; i.c. model: n(tumor/mice) = 9, P<0.01). 
      CONCLUSIONS: Our results indicate that [(18)F]FLT-PET may be useful for an early 
      evaluation of the response of GBM to TMZ chemotherapy in patients with glioma.
FAU - Viel, Thomas
AU  - Viel T
AD  - European Institute for Molecular Imaging (EIMI), Westfalische Wilhelms-University 
      (WWU), Munster, Germany.
FAU - Schelhaas, Sonja
AU  - Schelhaas S
FAU - Wagner, Stefan
AU  - Wagner S
FAU - Wachsmuth, Lydia
AU  - Wachsmuth L
FAU - Schwegmann, Katrin
AU  - Schwegmann K
FAU - Kuhlmann, Michael
AU  - Kuhlmann M
FAU - Faber, Cornelius
AU  - Faber C
FAU - Kopka, Klaus
AU  - Kopka K
FAU - Schafers, Michael
AU  - Schafers M
FAU - Jacobs, Andreas H
AU  - Jacobs AH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130704
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Biomarkers, Pharmacological)
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Alkylating/*pharmacology
MH  - Biomarkers, Pharmacological/analysis
MH  - Brain Neoplasms/*diagnosis/diagnostic imaging/drug therapy
MH  - Dacarbazine/*analogs & derivatives/pharmacology
MH  - Early Diagnosis
MH  - Female
MH  - *Fluorodeoxyglucose F18/administration & dosage
MH  - Glioblastoma/*diagnosis/diagnostic imaging/drug therapy
MH  - Humans
MH  - Injections, Intraventricular
MH  - Injections, Subcutaneous
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasms, Experimental/diagnosis/diagnostic imaging/drug therapy
MH  - Temozolomide
MH  - Tomography, Emission-Computed
MH  - Treatment Outcome
MH  - Tumor Burden/drug effects
PMC - PMC3701682
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/07/19 06:00
MHDA- 2014/02/04 06:00
PMCR- 2013/07/04
CRDT- 2013/07/18 06:00
PHST- 2012/12/15 00:00 [received]
PHST- 2013/05/22 00:00 [accepted]
PHST- 2013/07/18 06:00 [entrez]
PHST- 2013/07/19 06:00 [pubmed]
PHST- 2014/02/04 06:00 [medline]
PHST- 2013/07/04 00:00 [pmc-release]
AID - PONE-D-12-39584 [pii]
AID - 10.1371/journal.pone.0067911 [doi]
PST - epublish
SO  - PLoS One. 2013 Jul 4;8(7):e67911. doi: 10.1371/journal.pone.0067911. Print 2013.