title: Role of O-(2-(18)F-fluoroethyl)-L-tyrosine PET for differentiation of local recurrent brain metastasis from radiation necrosis.
abstract: The aim of this study was to investigate the potential of O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET for differentiating local recurrent brain metastasis from radiation necrosis after radiation therapy because the use of contrast-enhanced MRI for this issue is often difficult.
  
  
  METHODS
  Thirty-one patients (mean age ± SD, 53 ± 11 y) with single or multiple contrast-enhancing brain lesions (n = 40) on MRI after radiation therapy of brain metastases were investigated with dynamic (18)F-FET PET. Maximum and mean tumor-to-brain ratios (TBR(max) and TBR(mean), respectively; 20-40 min after injection) of (18)F-FET uptake were determined. Time-activity curves were generated, and the time to peak (TTP) was calculated. Furthermore, time-activity curves of each lesion were assigned to one of the following curve patterns: (I) constantly increasing (18)F-FET uptake, (II) (18)F-FET uptake peaking early (TTP ≤ 20 min) followed by a plateau, and (III) (18)F-FET uptake peaking early (TTP ≤ 20 min) followed by a constant descent. The diagnostic accuracy of the TBR(max) and TBR(mean) of (18)F-FET uptake and the curve patterns for the correct identification of recurrent brain metastasis were evaluated by receiver-operating-characteristic analyses or Fisher exact test for 2 × 2 contingency tables using subsequent histologic analysis (11 lesions in 11 patients) or clinical course and MRI findings (29 lesions in 20 patients) as reference.
  
  
  RESULTS
  Both TBR(max) and TBR(mean) were significantly higher in patients with recurrent metastasis (n = 19) than in patients with radiation necrosis (n = 21) (TBR(max), 3.2 ± 0.9 vs. 2.3 ± 0.5, P < 0.001; TBR(mean), 2.1 ± 0.4 vs. 1.8 ± 0.2, P < 0.001). The diagnostic accuracy of (18)F-FET PET for the correct identification of recurrent brain metastases reached 78% using TBR(max) (area under the ROC curve [AUC], 0.822 ± 0.07; sensitivity, 79%; specificity, 76%; cutoff, 2.55; P = 0.001), 83% using TBR(mean) (AUC, 0.851 ± 0.07; sensitivity, 74%; specificity, 90%; cutoff, 1.95; P < 0.001), and 92% for curve patterns II and III versus curve pattern I (sensitivity, 84%; specificity, 100%; P < 0.0001). The highest accuracy (93%) to diagnose local recurrent metastasis was obtained when both a TBR(mean) greater than 1.9 and curve pattern II or III were present (AUC, 0.959 ± 0.03; sensitivity, 95%; specificity, 91%; P < 0.001).
  
  
  CONCLUSIONS
  Our findings suggest that the combined evaluation of the TBR(mean) of (18)F-FET uptake and the pattern of the time-activity curve can differentiate local brain metastasis recurrence from radionecrosis with high accuracy. (18)F-FET PET may thus contribute significantly to the management of patients with brain metastases.
authors.affiliation: Institute of Neuroscience and Medicine (INM-3,-4,-5), Forschungszentrum Jülich, Jülich, Germany. N.Galldiks@fz-juelich.de
authors.forename: Norbert
authors.initials: N
authors.lastname: Galldiks
authors.forename: Gabriele
authors.initials: G
authors.lastname: Stoffels
authors.forename: Christian P
authors.initials: CP
authors.lastname: Filss
authors.forename: Marc D
authors.initials: MD
authors.lastname: Piroth
authors.forename: Michael
authors.initials: M
authors.lastname: Sabel
authors.forename: Maximilian I
authors.initials: MI
authors.lastname: Ruge
authors.forename: Hans
authors.initials: H
authors.lastname: Herzog
authors.forename: Nadim J
authors.initials: NJ
authors.lastname: Shah
authors.forename: Gereon R
authors.initials: GR
authors.lastname: Fink
authors.forename: Heinz H
authors.initials: HH
authors.lastname: Coenen
authors.forename: Karl-Josef
authors.initials: KJ
authors.lastname: Langen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001692:Biological Transport; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000556:secondary*; D003937:Diagnosis, Differential; D006801:Humans; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000000981:diagnostic imaging / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography; D012372:ROC Curve; D011832:Radiation Injuries / Q000000981:diagnostic imaging* / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D055815:Young Adult
chemical_list: C117289:O-(2-fluoroethyl)tyrosine; D014443:Tyrosine