Hot spots in dynamic18FET-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.

Dynamic 18F‐FET PET in suspected WHO grade II gliomas defines distinct biological subgroups with different clinical courses

“…The sample size calculation was done after completion of the descriptive part of the study. 20 On the basis of this initial work, we assumed that most tumors with increasing TAC pattern would represent grade II and those with decreasing TAC would represent grade III gliomas. In accordance with the WHO classification, 1 we did not expect a distinct prognosis of the focal decreasing as compared to the homogeneous decreasing TAC group.…”

“…11,18,19 For characterization of MRI-suspected low-grade gliomas by 18 F-FET PET, we had previously mapped the tumor volumes using dynamic 18 F-FET uptake analyses. 20 We have correlated the obtained TAC patterns with the corresponding histological findings and identified three characteristic TAC patterns: Tumors exhibiting increasing TAC throughout the tumor volume ("homogeneous increasing TAC group") and those exhibiting decreasing TAC either homogeneously throughout the tumor volume ("homogeneous decreasing TAC group") or only focally within a tumor volume with otherwise increasing TAC ("focal decreasing TAC group").…”

“…All consecutively included 55 patients of the initial (descriptive) analysis were also considered in the current report. 20 Informed consent was obtained from all patients. The study protocol was reviewed and approved by the ethical review board of the LudwigMaximilians University, Munich, Germany (AZ 216/14).…”

“…Serial biopsy samples were collected in 1 mm steps along a trajectory representative of the tumor inside and outside of the premarked hot spot, if present. 20 Using microforceps, the maximum amount of tissue per biopsy specimen was 1 mm 3 . For each of the collected biopsy specimens, the position on the defined trajectory and the distance from the predefined target point were exactly determined.…”

Diagnostic accuracy of F-18-fluoroethyltyrosine PET and PET/CT in patients with brain tumor

“…Qualitative FET-PET uptake does not allow tumor grading, but dynamic FET-PET analysis helps in the differentiation of low-from highgrade tumors [8]. FET-PET has also been shown to be valuable for guiding biopsy, diagnosing brain tumor recurrence after initial therapy, and directing radiosurgery [9]. As FET exhibits lower uptake by inflammatory cells than 11 C-methionine and FDG, it can be used for differentiating tumor from radionecrosis [10].…”