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Cornelius J.F.,Heinrich Heine University Düsseldorf | Stoffels G.,Jülich Research Center | Filss C.,Jülich Research Center | Galldiks N.,Jülich Research Center | And 13 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2014

Purpose: O-(2-[18F]Fluoroethyl)-l-tyrosine (18F-FET) is a well-established PET tracer for the imaging of cerebral gliomas, but little is known about 18F-FET uptake in meningiomas. The aim of this study was to explore 18F-FET kinetics and tumour-to-background contrast in meningiomas of various histologies.Methods: A group of 24 patients with suspected cerebral meningioma on MRI/CT had an additional dynamic 18F-FET PET scan prior to surgery. Time–activity curves (TAC) of 18F-FET uptake in the tumours and tumour-to-brain ratios (TBR) for early (3 – 14 min after injection) and late 18F-FET uptake (20 – 40 min after injection) were analysed and compared with histological subtypes and WHO grade. 18F-FET uptake in critical structures in the skull base was also evaluated in terms of tumour-to-tissue (T/Tis) ratio.Results: TBR of 18F-FET uptake in meningiomas was significantly higher in the early phase than in the late phase (3.5 ± 0.8 vs. 2.2 ± 0.3; P < 0.001). The difference in TBR between low-grade meningiomas (WHO grade I, 18 patients) and high-grade meningiomas (WHO grade II or III, 6 patients) was significant in the late phase of 18F-FET uptake (2.1 ± 0.2 vs. 2.5 ± 0.2, P = 0.003) while there was no significant difference in the early phase. ROC analysis showed that TBR of 18F-FET uptake in the late phase had significant power to differentiate low-grade from high-grade meningiomas (AUC 0.87 ± 0.18, sensitivity 83 %, specificity 83 %, optimal cut-off 2.3; P < 0.01). Evaluation of TAC yielded three different curve patterns of 18F-FET PET uptake. Combination of TBR (cut-off value 2.3) and TAC pattern slightly improved the differentiation of high-grade from low-grade meningiomas (accuracy 92 %; P = 0.001). Analysis of background radioactivity in the skull base indicated that 18F-FET uptake may be helpful in distinguishing meningioma tissue in the late phase. T/Tis ratios were >1.2 in all patients for the periorbita, sphenoidal sinus, pituitary gland, tentorium, bone and brain, in more than 90 % of patients for the mucosa and dura, but in only 63 % of patients for the cavernous sinus.Conclusion: 18F-FET PET may provide additional information for noninvasive grading of meningiomas and possibly for the discrimination of tumour in critical areas of the skull base. A further evaluation of 18F-FET PET in meningiomas appears to be justified. © 2014, Springer-Verlag Berlin Heidelberg.


Stegmayr C.,Jülich Research Center | Bandelow U.,Jülich Research Center | Oliveira D.,Jülich Research Center | Lohmann P.,Jülich Research Center | And 12 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2016

Purpose: O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) is an established tracer for the diagnosis of brain tumors with PET. This study investigates the influence of blood-brain barrier (BBB) permeability on 18F-FET uptake in two rat glioma models and one human xenograft model. Methods: F98 glioma, 9L gliosarcoma or human U87 glioblastoma cells were implanted into the striatum of 56 Fischer or RNU rats. Thereafter, animals were divided into a control group and a group receiving injections of the glucocorticoid dexamethasone (Dex). After 12-13 days of tumor growth animals received injection of Evans blue dye (EBD) to visualize BBB disturbance and underwent 18F-FET PET followed by autoradiography. Time activity curves, standardized uptake values (SUV) and Tumor-to-brain ratios (TBR) of 18F-FET uptake [18-61 min post injection (p.i.)] were evaluated using a volume-of-Interest (VOI) analysis. BBB disturbance was quantitatively evaluated by EBD fluorescence. The membrane gaps of blood vessel endothelial tight junctions were measured using electron microscopy to visualize ultrastructural BBB alterations in one untreated and one Dex treated F98 glioma. Data were analyzed by two-way ANOVAs. Results: In Dex treated animals EBD extravasation was significantly reduced in 9L (P < 0.001) and U87 (P = 0.008) models and showed a trend in F98 models (P = 0.053). In contrast, no significant differences of 18F-FET uptake were observed between Dex treated animals and control group except a decrease of the TBR in the 9L tumor model in PET (P < 0.01). Ultrastructural evaluation of tumor blood vessel endothelia revealed significant reduction of the cleft diameter between endothelial cells after Dex treatment in F98 model (P = 0.010). Conclusion: Despite a considerable reduction of BBB permeability in rat gliomas after Dex treatment, no relevant changes of 18F-FET uptake were noted in this experimental study. Thus, 18F-FET uptake in gliomas appears to be widely independent of the permeability of the BBB. © 2016 Springer-Verlag Berlin Heidelberg


Filss C.P.,Jülich Research Center | Stoffels G.,Jülich Research Center | Galldiks N.,Jülich Research Center | Galldiks N.,University of Cologne | And 12 more authors.
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2014

Anatomical imaging with magnetic resonance imaging (MRI) is currently the method of first choice for diagnostic investigation of glial tumors. However, different MR sequences may over- or underestimate tumor size and thus it may not be possible to delineate tumor from adjacent brain. In order to compensate this confinement additonal MR sequences like perfusion weighted MRI (PWI) with regional cerebral blood volume (rCBV) or positron emission tomography (PET) with aminoacids are used to gain further information. Recent studies suggest that both of theses image modalities provide similar diagnostic information. For comparison tumor to brain ratios (TBR) with mean and maximum values are frequently used but results from different studies can often not be checked against each other. Furthermore, especially the maximum TBR in rCBV is at risk to be falsified by artifacts (e.g. blood vessels). These confinements are reduced by the use of histograms since all information of the VOIs are equally displayed. In this study we measured and compared the intersection of tumor and reference tissue histograms in 18F-FET PET and rCBV maps in glioma patients. Methods Twenty-seven glioma patients with contrast enhancing lesion on T1-weighted MR images were investigated using static 18F-FET PET and rCBV in MRI using a PET-MR hybrid scanner. In all patients diagnosis was confirmed histologically (7 grade II gliomas, 6 grade III gliomas and 14 grade IV gliomas). We generated a set of tumor and reference tissue Volumes-of-Interest (VOIs) based on T1 weighted images in MRI with the tumor VOI defined by contrast enhancement and transferred these VOIs to the corresponding 18F-FET PET scans and rCBV maps. From these VOIs we generated tumor and reference tissue histograms with a unity of one for each curve integral and measured the proportion of the area under the tumor curve that falls into the reference curve for 18F-FET PET and rCBV maps for each patient. Results The mean proportion of the area under the tumor curve that falls into the reference curve was smaller in FET PET than in rCBV maps (13.1±19.5% vs. 45.0±21.3%; p<0.001). Conclusions Measuring the intersection of tumor and reference tissue histograms in 18F-FET PET and rCBV maps based on identical VOIs defined in anatomical images with tumor marked by contrast enhancement in T1-weighted images can easily be performed and indicates that tumor volume can better be discriminated from background in 18F-FET PET compared to rCBV in MRI. With this approach artefacts (e.g. blood vessels) impair the results to a lesser degree compared to the mean and especially maximal TBRs which are often used when comparing these two image modalities. © 2013 Elsevier B.V. All rights reserved.


Piroth M.D.,RWTH Aachen | Piroth M.D.,Julich Aachen Research Alliance JARA Section JARA Brain | Prasath J.,Jülich Research Center | Prasath J.,Julich Aachen Research Alliance JARA Section JARA Brain | And 18 more authors.
Nuclear Medicine and Biology | Year: 2013

PET using O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) allows improved imaging of tumor extent of cerebral gliomas in comparison to MRI. In experimental brain infarction and hematoma, an unspecific accumulation of 18F-FET has been detected in the area of reactive astrogliosis which is a common cellular reaction in the vicinity of cerebral gliomas. The aim of this study was to investigate possible 18F-FET uptake in the area of reactive gliosis in the vicinity of untreated and irradiated rat gliomas. Methods: F98-glioma cells were implanted into the caudate nucleus of 33 Fisher CDF rats. Sixteen animals remained untreated and in 17 animals the tumor was irradiated by Gamma Knife 5-8days after implantation (2/50Gy, 3/75Gy, 6/100Gy, 6/150Gy). After 8-17 days of tumor growth the animals were sacrificed following injection of 18F-FET. Brains were removed, cut in coronal sections and autoradiograms of 18F-FET distribution were produced and compared with histology (toluidine blue) and reactive astrogliosis (GFAP staining). 18F-FET uptake in the tumors and in areas of reactive astrocytosis was evaluated by lesion to brain ratios (L/B). Results: Large F98-gliomas were present in all animals showing increased 18F-FET-uptake which was similar in irradiated and non-irradiated tumors (L/B: 3.9±0.8 vs. 4.0±1.3). A pronounced reactive astrogliosis was noted in the vicinity of all tumors that showed significantly lower 18F-FET-uptake than the tumors (L/B: 1.5±0.4 vs. 3.9±1.1). The area of 18F-FET-uptake in the tumor was congruent with histological tumor extent in 31/33 animals. In 2 rats irradiated with 150Gy, however, high 18F-FET uptake was noted in the area of astrogliosis which led to an overestimation of the tumor size. Conclusions: Reactive astrogliosis in the vicinity of gliomas generally leads to only a slight 18F-FET-enrichment that appears not to affect the correct definition of tumor extent for treatment planning. © 2013 Elsevier Inc.


Lohmann P.,Jülich Research Center | Herzog H.,Jülich Research Center | Rota Kops E.,Jülich Research Center | Stoffels G.,Jülich Research Center | And 15 more authors.
European Radiology | Year: 2015

Objective: We aimed to evaluate the diagnostic potential of dual-time-point imaging with positron emission tomography (PET) using O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) for non-invasive grading of cerebral gliomas compared with a dynamic approach. Methods: Thirty-six patients with histologically confirmed cerebral gliomas (21 primary, 15 recurrent; 24 high-grade, 12 low-grade) underwent dynamic PET from 0 to 50 min post-injection (p.i.) of 18F-FET, and additionally from 70 to 90 min p.i. Mean tumour-to-brain ratios (TBRmean) of 18F-FET uptake were determined in early (20–40 min p.i.) and late (70–90 min p.i.) examinations. Time–activity curves (TAC) of the tumours from 0 to 50 min after injection were assigned to different patterns. The diagnostic accuracy of changes of 18F-FET uptake between early and late examinations for tumour grading was compared to that of curve pattern analysis from 0 to 50 min p.i. of 18F-FET. Results: The diagnostic accuracy of changes of the TBRmean of 18F-FET PET uptake between early and late examinations for the identification of HGG was 81 % (sensitivity 83 %; specificity 75 %; cutoff - 8 %; p < 0.001), and 83 % for curve pattern analysis (sensitivity 88 %; specificity 75 %; p < 0.001). Conclusion: Dual-time-point imaging of 18F-FET uptake in gliomas achieves diagnostic accuracy for tumour grading that is similar to the more time-consuming dynamic data acquisition protocol. Key Points: • Dual-time-point imaging is equivalent to dynamic FET PET for grading of gliomas. • Dual-time-point imaging is less time consuming than dynamic FET PET. • Costs can be reduced due to higher patient throughput. • Reduced imaging time increases patient comfort and sedation might be avoided. • Quicker image interpretation is possible, as no curve evaluation is necessary. © 2015, European Society of Radiology.

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