title: Diagnosis of pseudoprogression in patients with glioblastoma using O-(2-[18F]fluoroethyl)-L-tyrosine PET.
abstract: OBJECTIVE
  The follow-up of glioblastoma patients after radiochemotherapy with conventional MRI can be difficult since reactive alterations to the blood-brain barrier with contrast enhancement may mimic tumour progression (i.e. pseudoprogression, PsP). The aim of this study was to assess the clinical value of O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET in the differentiation of PsP and early tumour progression (EP) after radiochemotherapy of glioblastoma.
  
  
  METHODS
  A group of 22 glioblastoma patients with new contrast-enhancing lesions or lesions showing increased enhancement (>25 %) on standard MRI within the first 12 weeks after completion of radiochemotherapy with concomitant temozolomide (median 7 weeks) were additionally examined using amino acid PET with (18)F-FET. Maximum and mean tumour-to-brain ratios (TBRmax, TBRmean) were determined. (18)F-FET uptake kinetic parameters (i.e. patterns of time-activity curves, TAC) were also evaluated. Classification as PsP or EP was based on the clinical course (no treatment change at least for 6 months), follow-up MR imaging and/or histopathological findings. Imaging results were also related to overall survival (OS).
  
  
  RESULTS
  PsP was confirmed in 11 of the 22 patients. In patients with PsP, (18)F-FET uptake was significantly lower than in patients with EP (TBRmax 1.9 ± 0.4 vs. 2.8 ± 0.5, TBRmean 1.8 ± 0.2 vs. 2.3 ± 0.3; both P < 0.001) and presence of MGMT promoter methylation was significantly more frequent (P = 0.05). Furthermore, a TAC type II or III was more frequently present in patients with EP (P = 0.04). Receiver operating characteristic analysis showed that the optimal (18)F-FET TBRmax cut-off value for identifying PsP was 2.3 (sensitivity 100 %, specificity 91 %, accuracy 96 %, AUC 0.94 ± 0.06; P < 0.001). Univariate survival analysis showed that a TBRmax <2.3 predicted a significantly longer OS (median OS 23 vs. 12 months; P = 0.046).
  
  
  CONCLUSIONS
  (18)F-FET PET may facilitate the diagnosis of PsP following radiochemotherapy of glioblastoma.
authors.affiliation: Department of Neurology, University of Cologne, Cologne, Germany, Norbert.Galldiks@uk-koeln.de.
authors.forename: Norbert
authors.initials: N
authors.lastname: Galldiks
authors.forename: Veronika
authors.initials: V
authors.lastname: Dunkl
authors.forename: Gabriele
authors.initials: G
authors.lastname: Stoffels
authors.forename: Markus
authors.initials: M
authors.lastname: Hutterer
authors.forename: Marion
authors.initials: M
authors.lastname: Rapp
authors.forename: Michael
authors.initials: M
authors.lastname: Sabel
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.forename: Sied
authors.initials: S
authors.lastname: Kebir
authors.forename: Franziska
authors.initials: F
authors.lastname: Dorn
authors.forename: Tobias
authors.initials: T
authors.lastname: Blau
authors.forename: Ulrich
authors.initials: U
authors.lastname: Herrlinger
authors.forename: Peter
authors.initials: P
authors.lastname: Hau
authors.forename: Maximilian I
authors.initials: MI
authors.lastname: Ruge
authors.forename: Martin
authors.initials: M
authors.lastname: Kocher
authors.forename: Roland
authors.initials: R
authors.lastname: Goldbrunner
authors.forename: Gereon R
authors.initials: GR
authors.lastname: Fink
authors.forename: Alexander
authors.initials: A
authors.lastname: Drzezga
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmidt
authors.forename: Karl-Josef
authors.initials: KJ
authors.lastname: Langen
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D018450:Disease Progression; D005189:False Positive Reactions; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D014443:Tyrosine / Q000031:analogs & derivatives*
chemical_list: C117289:O-(2-fluoroethyl)tyrosine; D019275:Radiopharmaceuticals; D014443:Tyrosine