title: Methyl-L-11C-methionine PET as a diagnostic marker for malignant progression in patients with glioma.
abstract: Methyl-L-(11)C-methionine ((11)C-MET) PET has been shown to detect brain tumors with a high sensitivity and specificity. In this study, we investigated the potential of (11)C-MET PET to noninvasively detect tumor progression in patients with gliomas. Moreover, we analyzed the relationship between changes in (11)C-MET uptake on PET and changes in various molecular immunohistochemical markers during progression of gliomas.
  
  
  METHODS
  Twenty-four patients with histologically proven glioma were investigated repeatedly with (11)C-MET PET. (11)C-MET uptake was determined for a circular region of interest. Histologic and molecular analyses for tumor progression were performed after open surgery and stereotactic biopsy, respectively.
  
  
  RESULTS
  In patients with malignant progression, the mean increase in (11)C-MET uptake was 54.4% (SD, 45.5%; range, 3.1%-162.2%), whereas in patients without a change in tumor grade, mean (11)C-MET uptake did not significantly change (3.9%; SD, 13.7%; range, -24.4% to 26.3%). The difference in the change in (11)C-MET uptake between the group with malignant progression and the group without malignant progression was highly significant (P < 0.001). Receiver-operating-curve analysis revealed a sensitivity of 90% and a specificity of 92.3% for the detection of malignant transformation by an increase in (11)C-MET uptake of more than 14.6%. Increased (11)C-MET uptake of more than 14.6% was indicative of malignant progression in all but 3 leave-one-out iterations. A detailed immunohistochemical analysis demonstrated a significant correlation between changes in (11)C-MET uptake and the expression of vascular endothelial growth factor.
  
  
  CONCLUSIONS
  These data suggest that (11)C-MET-PET represents a noninvasive method to detect malignant progression in patients with gliomas. Moreover, the increase in (11)C-MET uptake during malignant progression is reflected by an increase in angiogenesis-promoting markers as vascular endothelial growth factor.
authors.affiliation: Max Planck Institute for Neurological Research with Klaus Joachim Zülch Laboratories, Cologne, Germany.
authors.forename: Roland T
authors.initials: RT
authors.lastname: Ullrich
authors.forename: Lutz
authors.initials: L
authors.lastname: Kracht
authors.forename: Anna
authors.initials: A
authors.lastname: Brunn
authors.forename: Karl
authors.initials: K
authors.lastname: Herholz
authors.forename: Peter
authors.initials: P
authors.lastname: Frommolt
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Miletic
authors.forename: Martina
authors.initials: M
authors.lastname: Deckert
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Heiss
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Jacobs
mesh_terms: D000293:Adolescent; D000328:Adult; D001692:Biological Transport; D002648:Child; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives*; D008875:Middle Aged; D049268:Positron-Emission Tomography; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D008715:Methionine; C038344:methionine methyl ester