title: Hot spots in dynamic (18)FET-PET delineate malignant tumor parts within suspected WHO grade II gliomas.
abstract: Molecular imaging studies have recently found inter- and intratumoral heterogeneity in World Health Organization (WHO) grade II gliomas. A correlative analysis with tumor histology, however, is still lacking. For elucidation we conducted the current prospective study. Fifty-five adult patients with an MRI-based suspicion of a WHO grade II glioma were included. [F-18]Fluoroethyltyrosine ((18)FET) uptake kinetic studies were combined with frame-based stereotactic localization techniques and used as a guide for stepwise (1-mm steps) histopathological evaluation throughout the tumor space. In tumors with heterogeneous PET findings, the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and expression of mutated protein isocitrate dehydrogenase variant R132H (IDH1) were determined inside and outside of hot spot volumes. Metabolic imaging revealed 3 subgroups: the homogeneous WHO grade II glioma group (30 patients), the homogeneous malignant glioma group (10 patients), and the heterogeneous group exhibiting both low- and high-grade characteristics at different sites (15 patients). Stepwise evaluation of 373 biopsy samples indicated a strong correlation with analyses of uptake kinetics (p < 0.0001). A homogeneous pattern of uptake kinetics was linked to homogeneous histopathological findings, whereas a heterogeneous pattern was associated with histopathological heterogeneity; hot spots exhibiting malignant glioma characteristics covered 4-44% of the entire tumor volumes. Both MGMT and IDH1 status were identical at different tumor sites and not influenced by heterogeneity. Maps of (18)FET uptake kinetics strongly correlated with histopathology in suspected grade II gliomas. Anaplastic foci can be accurately identified, and this finding has implications for prognostic evaluation and treatment planning.
authors.affiliation: Department of Neurosurgery, Klinikum Grosshadern, Ludwig Maximilians University Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kunz
authors.forename: N
authors.initials: N
authors.lastname: Thon
authors.forename: S
authors.initials: S
authors.lastname: Eigenbrod
authors.forename: C
authors.initials: C
authors.lastname: Hartmann
authors.forename: R
authors.initials: R
authors.lastname: Egensperger
authors.forename: J
authors.initials: J
authors.lastname: Herms
authors.forename: J
authors.initials: J
authors.lastname: Geisler
authors.forename: C
authors.initials: C
authors.lastname: la Fougere
authors.forename: J
authors.initials: J
authors.lastname: Lutz
authors.forename: J
authors.initials: J
authors.lastname: Linn
authors.forename: S
authors.initials: S
authors.lastname: Kreth
authors.forename: A
authors.initials: A
authors.lastname: von Deimling
authors.forename: J C
authors.initials: JC
authors.lastname: Tonn
authors.forename: H A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: G
authors.initials: G
authors.lastname: Pöpperl
authors.forename: F W
authors.initials: FW
authors.lastname: Kreth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics; D049268:Positron-Emission Tomography; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D014443:Tyrosine / Q000031:analogs & derivatives*; D014944:World Health Organization; D055815:Young Adult
chemical_list: D019275:Radiopharmaceuticals; C545932:(18F)fluoroethyltyrosine; D014443:Tyrosine; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D019853:O(6)-Methylguanine-DNA Methyltransferase