title: Serial 18F-FET PET Imaging of Primarily 18F-FET-Negative Glioma: Does It Make Sense?
abstract: PET with O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) has gained increasing importance for glioma management. With regard to the occurrence of (18)F-FET-negative glioma, we investigated the value of (18)F-FET PET monitoring of primarily (18)F-FET-negative gliomas concerning the detection of progression and malignant transformation.
  
  
  
  We included 31 patients (26 World Health Organization [WHO] grade II, 5 WHO grade III) with primarily (18)F-FET-negative glioma and available (18)F-FET PET follow-up. (18)F-FET PET analysis comprised maximal tumor-to-background ratio (TBRmax) and dynamic analysis of tumoral (18)F-FET uptake over time (increasing vs. decreasing) including minimal time to peak (TTPmin). PET findings were correlated with MRI and clinical findings of progression as well as histology of recurrent tumors.
  
  
  
  Twenty-three of 31 patients experienced tumor progression (median progression-free survival, 41.7 mo). Fourteen of 23 patients showed tumoral (18)F-FET uptake concurrent to and 4 of 23 before MRI-derived or clinical signs of tumor progression; 2 of 23 patients presented signs of progression in MRI when no concomitant (18)F-FET PET was available, but subsequent follow-up PET was positive. In 3 of 23 patients, no (18)F-FET uptake was detected at tumor progression. Overall, 20 of 31 primarily (18)F-FET-negative glioma turned (18)F-FET-positive during the follow-up. At first occurrence of tumoral (18)F-FET uptake, TBRmax was significantly higher in patients with malignant transformation (11/20) than in those without malignant progression (3.2 ± 0.9 vs. 1.9 ± 0.5; P = 0.001), resulting in a high detection rate for malignant transformation (for TBRmax > 2.46: sensitivity, 82%; specificity, 89%; negative predictive value, 80%; positive predictive value, 90%; and accuracy, 85%). Although static evaluation was superior to dynamic analysis for the detection of malignant transformation (for TTPmin ≤ 17.5 min: sensitivity, 73%; specificity, 67%; negative predictive value, 67%; positive predictive value, 73%; and accuracy, 70%), short TTPmin was associated with an early malignant transformation in the further disease course. Overall, 18 of 31 patients experienced malignant transformation; of these, 16 of 17 (94%) evaluable patients showed (18)F-FET uptake at the time of malignant transformation.
  
  
  
  (18)F-FET PET monitoring with static and dynamic evaluation is useful even in primarily (18)F-FET-negative glioma, providing a high detection rate of both tumor progression and malignant transformation, partly before further signs of progression in MRI. Hence, (18)F-FET uptake indicating malignant transformation might influence the patient management.
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Unterrainer
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schweisthal
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Bogdana
authors.initials: B
authors.lastname: Suchorska
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Wenter
authors.affiliation: Institute for Clinical Radiology, Ludwig-Maximilians-University, Munich, Germany; and.
authors.forename: Christine
authors.initials: C
authors.lastname: Schmid-Tannwald
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Wolfgang P
authors.initials: WP
authors.lastname: Fendler
authors.affiliation: Center for Neuropathology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schüller
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.affiliation: Department of Neurosurgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Jörg-Christian
authors.initials: JC
authors.lastname: Tonn
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University, Munich, Germany Nathalie.albert@med.uni-muenchen.de.
authors.forename: Nathalie L
authors.initials: NL
authors.lastname: Albert
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D003937:Diagnosis, Differential; D005188:False Negative Reactions; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013382:Subtraction Technique; D014443:Tyrosine / Q000031:analogs & derivatives*; D057832:Watchful Waiting / Q000379:methods*; D055815:Young Adult
chemical_list: D019275:Radiopharmaceuticals; C545932:(18F)fluoroethyltyrosine; D014443:Tyrosine
keywords: 18F-FET PET; glioma; kinetic analysis; monitoring; prognostic value