title: Early assessment of the efficacy of temozolomide chemotherapy in experimental glioblastoma using [18F]FLT-PET imaging.
abstract: 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.
authors.affiliation: European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms-University (WWU), Münster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Viel
authors.forename: Sonja
authors.initials: S
authors.lastname: Schelhaas
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagner
authors.forename: Lydia
authors.initials: L
authors.lastname: Wachsmuth
authors.forename: Katrin
authors.initials: K
authors.lastname: Schwegmann
authors.forename: Michael
authors.initials: M
authors.lastname: Kuhlmann
authors.forename: Cornelius
authors.initials: C
authors.lastname: Faber
authors.forename: Klaus
authors.initials: K
authors.lastname: Kopka
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D054316:Biomarkers, Pharmacological / Q000032:analysis; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000188:drug therapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D042241:Early Diagnosis; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage; D005909:Glioblastoma / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000188:drug therapy; D006801:Humans; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy; D000077204:Temozolomide; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D018906:Antineoplastic Agents, Alkylating; D054316:Biomarkers, Pharmacological; D019788:Fluorodeoxyglucose F18; D003606:Dacarbazine; D000077204:Temozolomide