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Background and Objectives: Clinical heterogeneity of patients with Parkinson disease (PD) is well recognized. PD with REM sleep behavior disorder (RBD) is a more malignant phenotype with faster motor progression and higher nonmotor symptom burden. However, the neural mechanisms underlying this clinical divergence concerning imbalances in neurotransmitter systems remain elusive., Methods: Combining magnetic resonance (MR) spectroscopy and [ 11 C]ABP688 PET on a PET/MR hybrid system, we simultaneously investigated two different mechanisms of glutamate signaling in patients with PD. Patients were grouped according to their RBD status in overnight video-polysomnography and compared with age-matched and sex-matched healthy control (HC) participants. Total volumes of distribution (V T ) of [ 11 C]ABP688 were estimated with metabolite-corrected plasma concentrations during steady-state conditions between 45 and 60 minutes of the scan following a bolus-infusion protocol. Glutamate, glutamine, and glutathione levels were investigated with single-voxel stimulated echo acquisition mode MR spectroscopy of the left basal ganglia., Results: We measured globally elevated V T of [ 11 C]ABP688 in 16 patients with PD and RBD compared with 17 patients without RBD and 15 HC participants ( F (2,45) = 5.579, p = 0.007). Conversely, glutamatergic metabolites did not differ between groups and did not correlate with the regional V T of [ 11 C]ABP688. V T of [ 11 C]ABP688 correlated with the amount of REM sleep without atonia ( F (1,42) = 5.600, p = 0.023) and with dopaminergic treatment response in patients with PD ( F (1,30) = 5.823, p = 0.022)., Discussion: Our results suggest that patients with PD and RBD exhibit altered glutamatergic signaling indicated by higher V T of [ 11 C]ABP688 despite unaffected glutamate levels. The imbalance of glutamate receptors and MR spectroscopy glutamate metabolite levels indicates a novel mechanism contributing to the heterogeneity of PD and warrants further investigation of drugs targeting mGluR5.

Purpose: Morphological imaging using MRI is essential for brain tumour diagnostics. Dynamic susceptibility contrast (DSC) perfusion-weighted MRI (PWI), as well as amino acid PET, may provide additional information in ambiguous cases. Since PWI is often unavailable in patients referred for amino acid PET, we explored whether maps of relative cerebral blood volume (rCBV) in brain tumours can be extracted from the early phase of PET using O-(2- 18 F-fluoroethyl)-L-tyrosine ( 18 F-FET)., Procedure: Using a hybrid brain PET/MRI scanner, PWI and dynamic 18 F-FET PET were performed in 33 patients with cerebral glioma and four patients with highly vascularized meningioma. The time interval from 0 to 2 min p.i. was selected to best reflect the blood pool phase in 18 F-FET PET. For each patient, maps of MR-rCBV, early 18 F-FET PET (0-2 min p.i.) and late 18 F-FET PET (20-40 min p.i.) were generated and coregistered. Volumes of interest were placed on the tumour (VOI-TU) and normal-appearing brain (VOI-REF). The correlation between tumour-to-brain ratios (TBR) of the different parameters was analysed. In addition, three independent observers evaluated MR-rCBV and early 18 F-FET maps ( 18 F-FET-rCBV) for concordance in signal intensity, tumour extent and intratumoural distribution., Results: TBRs calculated from MR-rCBV and 18 F-FET-rCBV showed a significant correlation (r = 0.89, p < 0.001), while there was no correlation between late 18 F-FET PET and MR-rCBV (r = 0.24, p = 0.16) and 18 F-FET-rCBV (r = 0.27, p = 0.11). Visual rating yielded widely agreeing findings or only minor differences between MR-rCBV maps and 18 F-FET-rCBV maps in 93 % of the tumours (range of three independent raters 91-94%, kappa among raters 0.78-1.0)., Conclusion: Early 18 F-FET maps (0-2 min p.i.) in gliomas provide similar information to MR-rCBV maps and may be helpful when PWI is not possible or available. Further studies in gliomas are needed to evaluate whether 18 F-FET-rCBV provides the same clinical information as MR-rCBV., (© 2023. The Author(s).)

Contrast-enhanced MRI is the method of choice for brain tumor diagnostics, despite its low specificity for tumor tissue. This study compared the contribution of MR spectroscopic imaging (MRSI) and amino acid PET to improve the detection of tumor tissue. Methods: In 30 untreated patients with suspected glioma, O -(2-[ 18 F]fluoroethyl)-l-tyrosine ( 18 F-FET) PET; 3-T MRSI with a short echo time; and fluid-attenuated inversion recovery, T2-weighted, and contrast-enhanced T1-weighted MRI were performed for stereotactic biopsy planning. Serial samples were taken along the needle trajectory, and their masks were projected to the preoperative imaging data. Each sample was individually evaluated neuropathologically. 18 F-FET uptake and the MRSI signals choline (Cho), N -acetyl-aspartate (NAA), creatine, myoinositol, and derived ratios were evaluated for each sample and classified using logistic regression. The diagnostic accuracy was evaluated by receiver operating characteristic analysis. Results: On the basis of the neuropathologic evaluation of tissue from 88 stereotactic biopsies, supplemented with 18 F-FET PET and MRSI metrics from 20 areas on the healthy-appearing contralateral hemisphere to balance the glioma/nonglioma groups, 18 F-FET PET identified glioma with the highest accuracy (area under the receiver operating characteristic curve, 0.89; 95% CI, 0.81-0.93; threshold, 1.4 × background uptake). Among the MR spectroscopic metabolites, Cho/NAA normalized to normal brain tissue showed the highest diagnostic accuracy (area under the receiver operating characteristic curve, 0.81; 95% CI, 0.71-0.88; threshold, 2.2). The combination of 18 F-FET PET and normalized Cho/NAA did not improve the diagnostic performance. Conclusion: MRI-based delineation of gliomas should preferably be supplemented by 18 F-FET PET., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: In glioma patients, tumor growth and subsequent treatments are associated with various types of brain lesions. We hypothesized that cognitive functioning in these patients critically depends on the maintained structural connectivity of multiple brain networks., Methods: The study included 121 glioma patients (median age, 52 years; median Eastern Cooperative Oncology Group performance score 1; CNS-WHO Grade 3 or 4) after multimodal therapy. Cognitive performance was assessed by 10 tests in 5 cognitive domains at a median of 14 months after treatment initiation. Hybrid amino acid PET/MRI using the tracer O-(2-[ 18 F]fluoroethyl)-L-tyrosine, a network-based cortical parcellation, and advanced tractography were used to generate whole-brain fiber count-weighted connectivity matrices. The matrices were applied to a cross-validated machine-learning model to identify predictive fiber connections (edges), critical cortical regions (nodes), and the networks underlying cognitive performance., Results: Compared to healthy controls ( n  = 121), patients' cognitive scores were significantly lower in 9 cognitive tests. The models predicted the scores of 7/10 tests (median correlation coefficient, 0.47; range, 0.39-0.57) from 0.6% to 5.4% of the matrix entries; 84% of the predictive edges were between nodes of different networks. Critically involved cortical regions (≥10 adjacent edges) included predominantly left-sided nodes of the visual, somatomotor, dorsal/ventral attention, and default mode networks. Highly critical nodes (≥15 edges) included the default mode network's left temporal and bilateral posterior cingulate cortex., Conclusions: These results suggest that the cognitive performance of pretreated glioma patients is strongly related to structural connectivity between multiple brain networks and depends on the integrity of known network hubs also involved in other neurological disorders., Competing Interests: N.G. has received honoraria from Telix Pharmaceuticals and Blue Earth Diagnostics. The other authors report no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Advanced MRI methods and PET using radiolabelled amino acids provide valuable information, in addition to conventional MR imaging, for brain tumour diagnostics. These methods are particularly helpful in challenging situations such as the differentiation of malignant processes from benign lesions, the identification of non-enhancing glioma subregions, the differentiation of tumour progression from treatment-related changes, and the early assessment of responses to anticancer therapy. The debate over which of the methods is preferable in which situation is ongoing, and has been addressed in numerous studies. Currently, most radiology and nuclear medicine departments perform these examinations independently of each other, leading to multiple examinations for the patient. The advent of hybrid PET/MRI allowed a convergence of the methods, but to date simultaneous imaging has reached little relevance in clinical neuro-oncology. This is partly due to the limited availability of hybrid PET/MRI scanners, but is also due to the fact that PET is a second-line examination in brain tumours. PET is only required in equivocal situations, and the spatial co-registration of PET examinations of the brain to previous MRI is possible without disadvantage. A key factor for the benefit of PET/MRI in neuro-oncology is a multimodal approach that provides decisive improvements in the diagnostics of brain tumours compared with a single modality. This review focuses on studies investigating the diagnostic value of combined amino acid PET and 'advanced' MRI in patients with cerebral gliomas. Available studies suggest that the combination of amino acid PET and advanced MRI improves grading and the histomolecular characterisation of newly diagnosed tumours. Few data are available concerning the delineation of tumour extent. A clear additive diagnostic value of amino acid PET and advanced MRI can be achieved regarding the differentiation of tumour recurrence from treatment-related changes. Here, the PET-guided evaluation of advanced MR methods seems to be helpful. In summary, there is growing evidence that a multimodal approach can achieve decisive improvements in the diagnostics of cerebral gliomas, for which hybrid PET/MRI offers optimal conditions.

PET imaging using radiolabeled amino acids in addition to MRI has become a valuable diagnostic tool in the clinical management of patients with brain tumors. This review provides a comprehensive overview of PET studies in glioma patients with a mutation in the isocitrate dehydrogenase gene (IDH). A considerable fraction of these tumors typically show no contrast enhancement on MRI, especially when classified as grade 2 according to the World Health Organization classification of Central Nervous System tumors. Major diagnostic challenges in this situation are differential diagnosis, target definition for diagnostic biopsies, delineation of glioma extent for treatment planning, differentiation of treatment-related changes from tumor progression, and the evaluation of response to alkylating agents. The main focus of this review is the role of amino acid PET in this setting. Furthermore, in light of clinical trials using IDH inhibitors targeting the mutated IDH enzyme for treating patients with IDH-mutant gliomas, we also aim to give an outlook on PET probes specifically targeting the IDH mutation, which appear potentially helpful for response assessment., (© 2022. The Author(s).)

Background: In glioma patients, multimodality therapy and recurrent tumor can lead to structural brain tissue damage characterized by pathologic findings in MR and PET imaging. However, little is known about the impact of different types of damage on the fiber architecture of the affected white matter., Patients and Methods: This study included 121 pretreated patients (median age, 52 years; ECOG performance score, 0 in 48%, 1-2 in 51%) with histomolecularly characterized glioma (WHO grade IV glioblastoma, n=81; WHO grade III anaplastic astrocytoma, n=28; WHO grade III anaplastic oligodendroglioma, n=12), who had a resection, radiotherapy, alkylating chemotherapy, or combinations thereof. After a median follow-up time of 14 months (range, 1-214 months), anatomic MR and O-(2-[ 18 F]fluoroethyl)-L-tyrosine (FET) PET images were acquired on a 3T hybrid PET/MR scanner. Post-therapeutic findings comprised resection cavities, regions with contrast enhancement or increased FET uptake and T2/FLAIR hyperintensities. Local fiber density was determined from high angular-resolution diffusion-weighted imaging and advanced tractography methods. A cohort of 121 healthy subjects selected from the 1000BRAINS study matched for age, gender and education served as a control group., Results: Lesion types differed in both affected tissue volumes and relative fiber densities compared to control values (resection cavities: median volume 20.9 mL, fiber density 16% of controls; contrast-enhanced lesions: 7.9 mL, 43%; FET uptake areas: 30.3 mL, 49%; T2/FLAIR hyperintensities: 53.4 mL, 57%, p<0.001). In T2/FLAIR-hyperintense lesions caused by peritumoral edema due to recurrent glioma (n=27), relative fiber density was as low as in lesions associated with radiation-induced gliosis (n=13, 48% vs. 53%, p=0.17). In regions with pathologically increased FET uptake, local fiber density was inversely related (p=0.005) to the extent of uptake. Total fiber loss associated with contrast-enhanced lesions (p=0.006) and T2/FLAIR hyperintense lesions (p=0.013) had a significant impact on overall ECOG score., Conclusions: These results suggest that apart from resection cavities, reduction in local fiber density is greatest in contrast-enhancing recurrent tumors, but total fiber loss induced by edema or gliosis has an equal detrimental effect on the patients' performance status due to the larger volume affected., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Friedrich, Farrher, Caspers, Lohmann, Lerche, Stoffels, Filss, Weiss Lucas, Ruge, Langen, Shah, Fink, Galldiks and Kocher.)

Purpose: To investigate the potential of radiomics applied to static clinical PET data using the tracer O-(2-[ 18 F]fluoroethyl)-L-tyrosine (FET) to differentiate treatment-related changes (TRC) from tumor progression (TP) in patients with gliomas., Patients and Methods: One hundred fifty-one (151) patients with histologically confirmed gliomas and post-therapeutic progressive MRI findings according to the response assessment in neuro-oncology criteria underwent a dynamic amino acid PET scan using the tracer O-(2-[ 18 F]fluoroethyl)-L-tyrosine (FET). Thereof, 124 patients were investigated on a stand-alone PET scanner (data used for model development and validation), and 27 patients on a hybrid PET/MRI scanner (data used for model testing). Mean and maximum tumor to brain ratios (TBR mean , TBR max ) were calculated using the PET data from 20 to 40 min after tracer injection. Logistic regression models were evaluated for the FET PET parameters TBR mean , TBR max , and for radiomics features of the tumor areas as well as combinations thereof to differentiate between TP and TRC. The best performing models in the validation dataset were finally applied to the test dataset. The diagnostic performance was assessed by receiver operating characteristic analysis., Results: Thirty-seven patients (25%) were diagnosed with TRC, and 114 (75%) with TP. The logistic regression model comprising the conventional FET PET parameters TBR mean and TBR max resulted in an AUC of 0.78 in both the validation (sensitivity, 64%; specificity, 80%) and the test dataset (sensitivity, 64%; specificity, 80%). The model combining the conventional FET PET parameters and two radiomics features yielded the best diagnostic performance in the validation dataset (AUC, 0.92; sensitivity, 91%; specificity, 80%) and demonstrated its generalizability in the independent test dataset (AUC, 0.85; sensitivity, 81%; specificity, 70%)., Conclusion: The developed radiomics classifier allows the differentiation between TRC and TP in pretreated gliomas based on routinely acquired static FET PET scans with a high diagnostic accuracy., (© 2022. The Author(s).)

O-(2-[ 18 F]fluoroethyl)-L-tyrosine (FET) is a widely used amino acid tracer for positron emission tomography (PET) imaging of brain tumours. This retrospective study and survey aimed to analyse our extensive database regarding the development of FET PET investigations, indications, and the referring physicians' rating concerning the role of FET PET in the clinical decision-making process. Between 2006 and 2019, we performed 6534 FET PET scans on 3928 different patients against a backdrop of growing demand for FET PET. In 2019, indications for the use of FET PET were as follows: suspected recurrent glioma (46%), unclear brain lesions (20%), treatment monitoring (19%), and suspected recurrent brain metastasis (13%). The referring physicians were neurosurgeons (60%), neurologists (19%), radiation oncologists (11%), general oncologists (3%), and other physicians (7%). Most patients travelled 50 to 75 km, but 9% travelled more than 200 km. The role of FET PET in decision-making in clinical practice was evaluated by a questionnaire consisting of 30 questions, which was filled out by 23 referring physicians with long experience in FET PET. Fifty to seventy per cent rated FET PET as being important for different aspects of the assessment of newly diagnosed gliomas, including differential diagnosis, delineation of tumour extent for biopsy guidance, and treatment planning such as surgery or radiotherapy, 95% for the diagnosis of recurrent glioma, and 68% for the diagnosis of recurrent brain metastases. Approximately 50% of the referring physicians rated FET PET as necessary for treatment monitoring in patients with glioma or brain metastases. All referring physicians stated that the availability of FET PET is essential and that it should be approved for routine use. Although the present analysis is limited by the fact that only physicians who frequently referred patients for FET PET participated in the survey, the results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for its approval for routine use.

Background: Motor response to dopaminergic therapy is a characteristic of patients with Parkinson's disease (PD). Whether nondopaminergic neurotransmitters contribute to treatment response is uncertain., Objectives: The aim of this study is to determine whether putaminal y-aminobutyric acid (GABA) levels are associated with dopaminergic motor response., Methods: We assessed putaminal GABA levels in 19 PD patients and 13 healthy controls (HCs) utilizing ultra-high field proton magnetic resonance spectroscopy. Motor performance was evaluated using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Part III, in the ON and OFF states. Statistical analysis comprised group comparisons, correlation analysis, and multiple linear regression., Results: In PD, GABA levels were significantly higher compared to HCs (1.50 ± 0.26 mM vs. 1.26 ± 0.31 mM, P = 0.022). Furthermore, GABA levels were independent predictors of absolute and relative dopaminergic treatment response., Conclusions: Our findings indicate that elevated putaminal GABA levels are associated with worse dopaminergic response in PD, emphasizing the essential role of nondopaminergic neurotransmitters in motor response. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Purpose: Perfusion-weighted MRI (PWI) and O-(2-[ 18 F]fluoroethyl-)-l-tyrosine ([ 18 F]FET) PET are both applied to discriminate tumor progression (TP) from treatment-related changes (TRC) in patients with suspected recurrent glioma. While the combination of both methods has been reported to improve the diagnostic accuracy, the performance of a sequential implementation has not been further investigated. Therefore, we retrospectively analyzed the diagnostic value of consecutive PWI and [ 18 F]FET PET., Methods: We evaluated 104 patients with WHO grade II-IV glioma and suspected TP on conventional MRI using PWI and dynamic [ 18 F]FET PET. Leakage corrected maximum relative cerebral blood volumes (rCBV max ) were obtained from dynamic susceptibility contrast PWI. Furthermore, we calculated static (i.e., maximum tumor to brain ratios; TBR max ) and dynamic [ 18 F]FET PET parameters (i.e., Slope). Definitive diagnoses were based on histopathology (n = 42) or clinico-radiological follow-up (n = 62). The diagnostic performance of PWI and [ 18 F]FET PET parameters to differentiate TP from TRC was evaluated by analyzing receiver operating characteristic and area under the curve (AUC)., Results: Across all patients, the differentiation of TP from TRC using rCBV max or [ 18 F]FET PET parameters was moderate (AUC = 0.69-0.75; p < 0.01). A rCBV max cutoff > 2.85 had a positive predictive value for TP of 100%, enabling a correct TP diagnosis in 44 patients. In the remaining 60 patients, combined static and dynamic [ 18 F]FET PET parameters (TBR max , Slope) correctly discriminated TP and TRC in a significant 78% of patients, increasing the overall accuracy to 87%. A subgroup analysis of isocitrate dehydrogenase (IDH) mutant tumors indicated a superior performance of PWI to [ 18 F]FET PET (AUC = 0.8/< 0.62, p < 0.01/≥ 0.3)., Conclusion: While marked hyperperfusion on PWI indicated TP, [ 18 F]FET PET proved beneficial to discriminate TP from TRC when PWI remained inconclusive. Thus, our results highlight the clinical value of sequential use of PWI and [ 18 F]FET PET, allowing an economical use of diagnostic methods. The impact of an IDH mutation needs further investigation.

Over the last years, the amount, variety, and complexity of neuroimaging data acquired in patients with brain tumors for routine clinical purposes and the resulting number of imaging parameters have substantially increased. Consequently, a timely and cost-effective evaluation of imaging data is hardly feasible without the support of methods from the field of artificial intelligence (AI). AI can facilitate and shorten various time-consuming steps in the image processing workflow, e.g., tumor segmentation, thereby optimizing productivity. Besides, the automated and computer-based analysis of imaging data may help to increase data comparability as it is independent of the experience level of the evaluating clinician. Importantly, AI offers the potential to extract new features from the routinely acquired neuroimages of brain tumor patients. In combination with patient data such as survival, molecular markers, or genomics, mathematical models can be generated that allow, for example, the prediction of treatment response or prognosis, as well as the noninvasive assessment of molecular markers. The subdiscipline of AI dealing with the computation, identification, and extraction of image features, as well as the generation of prognostic or predictive mathematical models, is termed radiomics. This review article summarizes the basics, the current workflow, and methods used in radiomics with a focus on feature-based radiomics in neuro-oncology and provides selected examples of its clinical application., (Copyright © 2020 Elsevier Inc. All rights reserved.)

PET using O -(2- 18 F-fluoroethyl)-l-tyrosine ( 18 F-FET) is useful to detect residual tumor tissue after glioma resection. Recent animal experiments detected reactive changes in 18 F-FET uptake at the rim of the resection cavity within the first 2 wk after resection of gliomas. In the present study, we evaluated pre- and postoperative 18 F-FET PET scans of glioma patients with particular emphasis on the identification of reactive changes after surgery. Methods: Forty-three patients with cerebral gliomas (9 low-grade, 34 high-grade; 9 primary tumors, 34 recurrent tumors) who had preoperative (time before surgery: median, 23 d; range, 6-44 d) and postoperative 18 F-FET PET (time after surgery: median, 14 d; range, 5-28 d) were included. PET scans (20-40 min after injection) were evaluated visually for complete or incomplete resection and compared with MRI. Changes in 18 F-FET uptake were evaluated by tumor-to-brain ratios in residual tumor and by maximum lesion-to-brain ratios near the resection cavity. Results: Visual analysis of 18 F-FET PET scans revealed complete resection in 16 of 43 patients and incomplete resection in the remaining patients. PET results were concordant with MRI in 69% of the patients. The maximum lesion-to-brain ratio for 18 F-FET uptake near the resection cavity was significantly higher than preoperative values (1.59 ± 0.36 vs. 1.14 ± 0.17; n = 43; P < 0.001). In 11 patients (26%), a flare phenomenon was observed, with a considerable increase in 18 F-FET uptake compared with preoperative values in either the residual tumor ( n = 5) or areas remote from the tumor on the preoperative PET scan ( n = 6) (2.92 ± 1.24 vs. 1.62 ± 0.75; P < 0.001). Further follow-up in 5 patients showed decreasing 18 F-FET uptake in the flare areas in 4 patients and progress in 1 patient. Conclusion: Our study confirmed that 18 F-FET PET provides valuable information for assessing the success of glioma resection. Postoperative reactive changes at the rim of the resection cavity appear to be mild. However, in 23% of the patients, a postoperative flare phenomenon was observed that warrants further investigation., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: Integrated histomolecular diagnostics of gliomas according to the World Health Organization (WHO) classification of 2016 has refined diagnostic accuracy and prediction of prognosis. This study aimed at exploring the prognostic value of dynamic O-(2-[ 18 F]-fluoroethyl)-L-tyrosine (FET) PET in newly diagnosed, histomolecularly classified astrocytic gliomas of WHO grades III or IV., Methods: Before initiation of treatment, dynamic FET PET imaging was performed in patients with newly diagnosed glioblastoma (GBM) and anaplastic astrocytoma (AA). Static FET PET parameters such as maximum and mean tumour/brain ratios (TBR max/mean ), the metabolic tumour volume (MTV) as well as the dynamic FET PET parameters time-to-peak (TTP) and slope, were obtained. The predictive ability of FET PET parameters was evaluated concerning the progression-free and overall survival (PFS, OS). Using ROC analyses, threshold values for FET PET parameters were obtained. Subsequently, univariate Kaplan-Meier and multivariate Cox regression survival analyses were performed to assess the predictive power of these parameters for survival., Results: Sixty patients (45 GBM and 15 AA patients) of two university centres were retrospectively identified. Patients with isocitrate dehydrogenase (IDH)-mutant or O 6 -methylguanine-DNA-methyltransferase (MGMT) promoter-methylated tumours had a significantly longer PFS and OS (both P < 0.001). Furthermore, ROC analysis of IDH-wildtype glioma patients (n = 45) revealed that a TTP > 25 min (AUC, 0.90; sensitivity, 90%; specificity, 87%; P < 0.001) was highly prognostic for longer PFS (13 vs. 7 months; P = 0.005) and OS (29 vs. 12 months; P < 0.001). In contrast, at a lower level of significance, TBR max , TBR mean , and MTV were only prognostic for longer OS (P = 0.004, P = 0.038, and P = 0.048, respectively). Besides complete resection and a methylated MGMT promoter, TTP remained significant in multivariate survival analysis (all P ≤ 0.02), indicating an independent predictor for OS., Conclusions: Our data suggest that dynamic FET PET allows the identification of patients with longer OS among patients with newly diagnosed IDH-wildtype GBM and AA.

In glioma patients, differentiation between tumor progression (TP) and treatment-related changes (TRCs) remains challenging. Difficulties in classifying imaging alterations may result in a delay or an unnecessary discontinuation of treatment. PET using O -(2- 18 F-fluoroethyl)-l-tyrosine ( 18 F-FET) has been shown to be a useful tool for detecting TP and TRCs. Methods: We retrospectively evaluated 127 consecutive patients with World Health Organization grade II-IV glioma who underwent 18 F-FET PET imaging to distinguish between TP and TRCs. 18 F-FET PET findings were verified by neuropathology (40 patients) or clinicoradiologic follow-up (87 patients). Maximum tumor-to-brain ratios (TBR max ) of 18 F-FET uptake and the slope of the time-activity curves (20-50 min after injection) were determined. The diagnostic accuracy of 18 F-FET PET parameters was evaluated by receiver-operating-characteristic analysis and χ 2 testing. The prognostic value of 18 F-FET PET was estimated using the Kaplan-Meier method. Results: TP was diagnosed in 94 patients (74%) and TRCs in 33 (26%). For differentiating TP from TRCs, receiver-operating-characteristic analysis yielded an optimal 18 F-FET TBR max cutoff of 1.95 (sensitivity, 70%; specificity, 71%; accuracy, 70%; area under the curve, 0.75 ± 0.05). The highest accuracy was achieved by a combination of TBR max and slope (sensitivity, 86%; specificity, 67%; accuracy, 81%). However, accuracy was poorer when tumors harbored isocitrate dehydrogenase ( IDH ) mutations (91% in IDH -wild-type tumors, 67% in IDH -mutant tumors, P < 0.001). 18 F-FET PET results correlated with overall survival ( P < 0.001). Conclusion: In our neurooncology department, the diagnostic performance of 18 F-FET PET was convincing but slightly inferior to that of previous reports., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Objectives: Recent research suggested an influence of diminished central nervous serotonin (5-HT) synthesis on the leptin axis via immunological mechanisms in healthy adult females. However, studies assessing immunological parameters in combination with dietary challenge techniques that impact brain 5-HT synthesis in humans are lacking.  Methods: In the present trial, a pilot analysis was conducted on data obtained in healthy adult humans receiving either different dietary acute tryptophan depletion (ATD) challenge or tryptophan (TRP)-balanced control conditions (BAL) to study the effects of reduced central nervous 5-HT synthesis on serum tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and IL-6 concentrations. The data of N = 35 healthy adults were analysed who were randomly subjected to one of the following two dietary conditions in a double-blind between-subject approach: (1) The Moja-De ATD challenge (ATD), or (2) TRP-balanced control condition for ATD Moja-De (BAL). Serum concentrations for the assessment of relevant parameters (TNF-α, IL-1β and IL-6) and relevant TRP-related characteristics after the respective challenge procedures were assessed at baseline (T0) and in hourly intervals after administration over a period of 6 h (T1-T6).  Results: The ATD condition did not result in significant changes to cytokine concentrations for the entire study sample, or in male and female subgroups. Depletion of CNS 5-HT via dietary TRP depletion appears to have no statistically significant short-term impact on cytokine concentrations in healthy adults.  Conclusions: Future research on immunological stressors in combination with challenge techniques will be of value in order to further disentangle the complex interplay between brain 5-HT synthesis and immunological pathways.

Mutations in the isocitrate dehydrogenase (IDH mut) gene have gained paramount importance for the prognosis of glioma patients. To date, reliable techniques for a preoperative evaluation of IDH genotype remain scarce. Therefore, we investigated the potential of O-(2-[ 18 F]fluoroethyl)-L-tyrosine (FET) PET radiomics using textural features combined with static and dynamic parameters of FET uptake for noninvasive prediction of IDH genotype. Prior to surgery, 84 patients with newly diagnosed and untreated gliomas underwent FET PET using a standard scanner (15 of 56 patients with IDH mut) or a dedicated high-resolution hybrid PET/MR scanner (11 of 28 patients with IDH mut). Static, dynamic and textural parameters of FET uptake in the tumor area were evaluated. Diagnostic accuracy of the parameters was evaluated using the neuropathological result as reference. Additionally, FET PET and textural parameters were combined to further increase the diagnostic accuracy. The resulting models were validated using cross-validation. Independent of scanner type, the combination of standard PET parameters with textural features increased significantly diagnostic accuracy. The highest diagnostic accuracy of 93% for prediction of IDH genotype was achieved with the hybrid PET/MR scanner. Our findings suggest that the combination of conventional FET PET parameters with textural features provides important diagnostic information for the non-invasive prediction of the IDH genotype.

Objective: To compare the diagnostic performance of O-(2- 18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) positron emission tomography (PET) and perfusion-weighted magnetic resonance imaging (PWI) for the diagnosis of progressive or recurrent glioma., Methods: Thirty-two pretreated gliomas (25 progressive or recurrent tumors, 7 treatment-related changes) were investigated with 18 F-FET PET and PWI via a hybrid PET/magnetic resonance scanner. Volumes of interest with a diameter of 16 mm were centered on the maximum of abnormality in the tumor area in PET and PWI maps (relative cerebral blood volume, relative cerebral blood flow, mean transit time) and the contralateral unaffected hemisphere. Mean and maximum tumor-to-brain ratios as well as dynamic data for 18 F-FET uptake were calculated. Diagnostic accuracies were evaluated by receiver operating characteristic analyses, calculating the area under the curve., Results: 18 F-FET PET showed a significant greater sensitivity to detect abnormalities in pretreated gliomas than PWI (76% vs. 52%, P = 0.03). The maximum tumor-to-brain ratio of 18 F-FET PET was the only parameter that discriminated treatment-related changes from progressive or recurrent gliomas (area under the curve, 0.78; P = 0.03, best cut-off 2.61; sensitivity 80%, specificity 86%, accuracy 81%). Among patients with signal abnormality in both modalities, 75% revealed spatially incongruent local hot spots., Conclusions: This pilot study suggests that 18 F-FET PET is superior to PWI to diagnose progressive or recurrent glioma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Both perfusion-weighted MR imaging (PWI) and O-(2- 18 F-fluoroethyl)-L-tyrosine PET ( 18 F-FET) provide grading information in cerebral gliomas. The aim of this study was to compare the diagnostic value of 18 F-FET PET and PWI for tumor grading in a series of patients with newly diagnosed, untreated gliomas using an integrated PET/MR scanner., Methods: Seventy-two patients with untreated gliomas [22 low-grade gliomas (LGG), and 50 high-grade gliomas (HGG)] were investigated with 18 F-FET PET and PWI using a hybrid PET/MR scanner. After visual inspection of PET and PWI maps (rCBV, rCBF, MTT), volumes of interest (VOIs) with a diameter of 16 mm were centered upon the maximum of abnormality in the tumor area in each modality and the contralateral unaffected hemisphere. Mean and maximum tumor-to-brain ratios (TBR mean , TBR max ) were calculated. In addition, Time-to-Peak (TTP) and slopes of time-activity curves were calculated for 18 F-FET PET. Diagnostic accuracies of 18 F-FET PET and PWI for differentiating low-grade glioma (LGG) from high-grade glioma (HGG) were evaluated by receiver operating characteristic analyses (area under the curve; AUC)., Results: The diagnostic accuracy of 18 F-FET PET and PWI to discriminate LGG from HGG was similar with highest AUC values for TBR mean and TBR max of 18 F-FET PET uptake (0.80, 0.83) and for TBR mean and TBR max of rCBV (0.80, 0.81). In case of increased signal in the tumor area with both methods (n = 32), local hot-spots were incongruent in 25 patients (78%) with a mean distance of 10.6 ± 9.5 mm. Dynamic FET PET and combination of different parameters did not further improve diagnostic accuracy., Conclusions: Both 18 F-FET PET and PWI discriminate LGG from HGG with similar diagnostic performance. Regional abnormalities in the tumor area are usually not congruent indicating that tumor grading by 18 F-FET PET and PWI is based on different pathophysiological phenomena.

Background: PET using O-(2-[ 18 F]fluoroethyl)-L-tyrosine ( 18 F-FET) is an established method for brain tumour diagnostics, but data processing varies in different centres. This study analyses the influence of methodological differences between two centres for tumour characterization with 18 F-FET PET using the same PET scanner. Methodological differences between centres A and B in the evaluation of 18 F-FET PET data were identified for (1) framing of PET dynamic data, (2) data reconstruction, (3) cut-off values for tumour delineation to determine tumour-to-brain ratios (TBR) and tumour volume (T vol ) and (4) ROI definition to determine time activity curves (TACs) in the tumour. Based on the 18 F-FET PET data of 40 patients with untreated cerebral gliomas (20 WHO grade II, 10 WHO grade III, 10 WHO grade IV), the effect of different data processing in the two centres on TBR mean , TBR max , T vol , time-to-peak (TTP) and slope of the TAC was compared. Further, the effect on tumour grading was evaluated by ROC analysis., Results: Significant differences between centres A and B were found especially for TBR max (2.84 ± 0.99 versus 3.34 ± 1.13; p < 0.001), T vol (1.14 ± 1.28 versus 1.51 ± 1.44; p < 0.001) and TTP (22.4 ± 8.3 min versus 30.8 ± 6.3 min; p < 0.001) and minor differences for TBR mean and slope. Tumour grading was not influenced by different data processing., Conclusions: Variable data processing of 18 F-FET PET in different centres leads to significant differences especially for TBR max and T vol . A standardization of data processing and evaluation is needed to make 18 F-FET PET comparable between different centres.

Objectives: We investigated the potential of textural feature analysis of O-(2-[ 18 F]fluoroethyl)-L-tyrosine ( 18 F-FET) PET to differentiate radiation injury from brain metastasis recurrence., Methods: Forty-seven patients with contrast-enhancing brain lesions (n = 54) on MRI after radiotherapy of brain metastases underwent dynamic 18 F-FET PET. Tumour-to-brain ratios (TBRs) of 18 F-FET uptake and 62 textural parameters were determined on summed images 20-40 min post-injection. Tracer uptake kinetics, i.e., time-to-peak (TTP) and patterns of time-activity curves (TAC) were evaluated on dynamic PET data from 0-50 min post-injection. Diagnostic accuracy of investigated parameters and combinations thereof to discriminate between brain metastasis recurrence and radiation injury was compared., Results: Diagnostic accuracy increased from 81 % for TBR mean alone to 85 % when combined with the textural parameter Coarseness or Short-zone emphasis. The accuracy of TBR max alone was 83 % and increased to 85 % after combination with the textural parameters Coarseness, Short-zone emphasis, or Correlation. Analysis of TACs resulted in an accuracy of 70 % for kinetic pattern alone and increased to 83 % when combined with TBR max ., Conclusions: Textural feature analysis in combination with TBRs may have the potential to increase diagnostic accuracy for discrimination between brain metastasis recurrence and radiation injury, without the need for dynamic 18 F-FET PET scans., Key Points: • Textural feature analysis provides quantitative information about tumour heterogeneity • Textural features help improve discrimination between brain metastasis recurrence and radiation injury • Textural features might be helpful to further understand tumour heterogeneity • Analysis does not require a more time consuming dynamic PET acquisition.

Background: The aim of this study was to investigate the potential of dynamic O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) PET for differentiating local recurrent brain metastasis from radiation injury after radiotherapy since contrast-enhanced MRI often remains inconclusive., Methods: Sixty-two patients (mean age, 55 ± 11 y) with single or multiple contrast-enhancing brain lesions (n = 76) on MRI after radiotherapy of brain metastases (predominantly stereotactic radiosurgery) were investigated with dynamic 18F-FET PET. Maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) of 18F-FET uptake were determined (20-40 min postinjection) as well as tracer uptake kinetics (ie, time-to-peak and slope of time-activity curves). Diagnoses were confirmed histologically (34%; 26 lesions in 25 patients) or by clinical follow-up (66%; 50 lesions in 37 patients). Diagnostic accuracies of PET parameters for the correct identification of recurrent brain metastasis were evaluated by receiver-operating-characteristic analyses or the chi-square test., Results: TBRs were significantly higher in recurrent metastases (n = 36) than in radiation injuries (n = 40) (TBRmax 3.3 ± 1.0 vs 2.2 ± 0.4, P < .001; TBRmean 2.2 ± 0.4 vs 1.7 ± 0.3, P < .001). The highest accuracy (88%) for diagnosing local recurrent metastasis could be obtained with TBRs in combination with the slope of time-activity curves (P < .001)., Conclusions: The results of this study confirm previous preliminary observations that the combined evaluation of the TBRs of 18F-FET uptake and the slope of time-activity curves can differentiate local brain metastasis recurrence from radiation-induced changes with high accuracy. 18F-FET PET may thus contribute significantly to the management of patients with brain metastases., (© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Purpose: Despite the excellent capacity of the conventional MRI to image brain tumours, problems remain in answering a number of critical diagnostic questions. To overcome these diagnostic shortcomings, PET using radiolabeled amino acids and perfusion-weighted imaging (PWI) are currently under clinical evaluation. The role of amino acid PET and PWI in different diagnostic challenges in brain tumours is controversial., Methods: Based on the literature and experience of our centres in correlative imaging with PWI and PET using O -(2-[ 18 F]fluoroethyl)-l-tyrosine or 3,4-dihydroxy-6-[ 18 F]-fluoro-l-phenylalanine, the current role and shortcomings of amino acid PET and PWI in different diagnostic challenges in brain tumours are reviewed. Literature searches were performed on PubMed, and additional literature was retrieved from the reference lists of identified articles. In particular, all studies in which amino acid PET was directly compared with PWI were included., Results: PWI is more readily available, but requires substantial expertise and is more sensitive to artifacts than amino acid PET. At initial diagnosis, PWI and amino acid PET can help to define a site for biopsy but amino acid PET appears to be more powerful to define the tumor extent. Both methods are helpful to differentiate progression or recurrence from unspecific posttherapeutic changes. Assessment of therapeutic efficacy can be achieved especially with amino acid PET, while the data with PWI are sparse., Conclusion: Both PWI and amino acid PET add valuable diagnostic information to the conventional MRI in the assessment of patients with brain tumours, but further studies are necessary to explore the complementary nature of these two methods.

Purpose: To compare the diagnostic information obtained with 6-[(18)F]-fluoro-L-3,4-dihydroxyphenylalanine (F-DOPA) PET and relative cerebral blood volume (rCBV) maps in recurrent or progressive glioma., Methods: All patients with recurrent or progressive glioma referred for F-DOPA imaging at our institution between May 2010 and May 2014 were retrospectively included, provided that macroscopic disease was visible on conventional MRI images and that rCBV maps were available for comparison. The final analysis included 50 paired studies (44 patients). After image registration, automatic tumour segmentation of both sets of images was performed using the average signal in a large reference VOI including grey and white matter multiplied by 1.6. Tumour volumes identified by both modalities were compared and their spatial congruence calculated. The distances between F-DOPA uptake and rCBV hot spots, tumour-to-brain ratios (TBRs) and normalized histograms were also computed., Results: On visual inspection, 49 of the 50 F-DOPA and 45 of the 50 rCBV studies were classified as positive. The tumour volume delineated using F-DOPA (F-DOPAvol 1.6) greatly exceeded that of rCBV maps (rCBVvol 1.6). The median F-DOPAvol 1.6 and rCBVvol 1.6 were 11.44 ml (range 0 - 220.95 ml) and 1.04 ml (range 0 - 26.30 ml), respectively (p < 0.00001). Overall, the median overlapping volume was 0.27 ml, resulting in a spatial congruence of 1.38 % (range 0 - 39.22 %). The mean hot spot distance was 27.17 mm (±16.92 mm). F-DOPA uptake TBR was significantly higher than rCBV TBR (1.76 ± 0.60 vs. 1.15 ± 0.52, respectively; p < 0.0001). The histogram analysis showed that F-DOPA provided better separation of tumour from background. In 6 of the 50 studies (12 %), however, physiological uptake in the striatum interfered with tumour delineation., Conclusion: The information provided by F-DOPA PET and rCBV maps are substantially different. Image interpretation is easier and a larger tumour extent is identified on F-DOPA PET images than on rCBV maps. The clinical impact of such differences needs to be explored in future studies.

Unlabelled: PET using O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) provides important diagnostic information in addition to that from conventional MR imaging on tumor extent and activity of cerebral gliomas. Recent studies suggest that perfusion-weighted MR imaging (PWI), especially maps of regional cerebral blood volume (rCBV), may provide similar diagnostic information. In this study, we directly compared (18)F-FET PET and PWI in patients with brain tumors., Methods: Fifty-six patients with gliomas were investigated using static (18)F-FET PET and PWI. For comparison, 8 patients with meningiomas were included. We generated a set of tumor and reference volumes of interest (VOIs) based on morphologic MR imaging and transferred these VOIs to the corresponding (18)F-FET PET scans and PWI maps. From these VOIs, tumor-to-brain ratios (TBR) were calculated, and normalized histograms were generated for (18)F-FET PET and rCBV maps. Furthermore, in rCBV maps and in (18)F-FET PET scans, tumor volumes, their spatial congruence, and the distance between the local hot spots were assessed., Results: For patients with glioma, TBR was significantly higher in (18)F-FET PET than in rCBV maps (TBR, 2.28 ± 0.99 vs. 1.62 ± 1.13; P < 0.001). Histogram analysis of the VOIs revealed that (18)F-FET scans could clearly separate tumor from background. In contrast, deriving this information from rCBV maps was difficult. Tumor volumes were significantly larger in (18)F-FET PET than in rCBV maps (tumor volume, 24.3 ± 26.5 cm(3) vs. 8.9 ± 13.9 cm(3); P < 0.001). Accordingly, spatial overlap of both imaging parameters was poor (congruence, 11.0%), and mean distance between the local hot spots was 25.4 ± 16.1 mm. In meningioma patients, TBR was higher in rCBV maps than in (18)F-FET PET (TBR, 5.33 ± 2.63 vs. 2.37 ± 0.32; P < 0.001) whereas tumor volumes were comparable., Conclusion: In patients with cerebral glioma, tumor imaging with (18)F-FET PET and rCBV yields different information. (18)F-FET PET shows considerably higher TBRs and larger tumor volumes than rCBV maps. The spatial congruence of both parameters is poor. The locations of the local hot spots differ considerably. Taken together, our data show that metabolically active tumor tissue of gliomas as depicted by amino acid PET is not reflected by rCBV as measured with PWI.

Proline and hydroxyproline represent major constituents of mammalian structural proteins, especially of collagen. An efficient radiosynthesis of the (18)F-labeled proline derivatives cis-/trans-4-[(18)F]fluoro-L-proline was developed two decades ago with the aim to investigate various diseases with altered collagen synthesis using Positron-Emission- Tomography (PET). A number of studies have explored cis-4-[(18)F]fluoro-L-proline uptake in various pathologies associated with increased collagen formation and in neoplastic lesions, but so far the results have not been very promising. Trans-4-[(18)F]fluoro-L-proline has not yet been investigated in detail, however the compound exhibits considerable differences in metabolic behavior and biodistribution compared with its cis-enantiomer. In recent years, the D-isomers of cis- /trans-4-[(18)F]fluoro-proline have been considered as PET tracers as well, and it was observed that both exhibit a preferred uptake into the brain compared with their L-isomers. Surprisingly, a high uptake of cis-4-[(18)F]fluoro-D-proline was found in brain areas exhibiting secondary neurodegeneration as well as in areas of radionecrosis after treatment of brain tumors. In this article, the present knowledge on the biological and physiological properties of cis-/trans-4-[(18)F]fluoro-D/L-proline and the results in various pathologies are reviewed, including some previously unpublished results from our laboratory.

Unlabelled: 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)., Conclusion: 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.

Unlabelled: The assessment of treatment response in glioblastoma is difficult with MRI because reactive blood-brain barrier alterations with contrast enhancement can mimic tumor progression. In this study, we investigated the predictive value of PET using O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET PET) during treatment., Methods: In a prospective study, 25 patients with glioblastoma were investigated by MRI and (18)F-FET PET after surgery (MRI-/FET-1), early (7-10 d) after completion of radiochemotherapy with temozolomide (RCX) (MRI-/FET-2), and 6-8 wk later (MRI-/FET-3). Maximum and mean tumor-to-brain ratios (TBR(max) and TBR(mean), respectively) were determined by region-of-interest analyses. Furthermore, gadolinium contrast-enhancement volumes on MRI (Gd-volume) and tumor volumes in (18)F-FET PET images with a tumor-to-brain ratio greater than 1.6 (T(vol 1.6)) were calculated using threshold-based volume-of-interest analyses. The patients were grouped into responders and nonresponders according to the changes of these parameters at different cutoffs, and the influence on progression-free survival and overall survival was tested using univariate and multivariate survival analyses and by receiver-operating-characteristic analyses., Results: Early after completion of RCX, a decrease of both TBR(max) and TBR(mean) was a highly significant and independent statistical predictor for progression-free survival and overall survival. Receiver-operating-characteristic analysis showed that a decrease of the TBR(max) between FET-1 and FET-2 of more than 20% predicted favorable survival [corrected], with a sensitivity of 83% and a specificity of 67% (area under the curve, 0.75). Six to eight weeks later, the predictive value of TBR(max) and TBR(mean) was less significant, but an association between a decrease of T(vol 1.6) and PFS was noted. In contrast, Gd-volume changes had no significant predictive value for survival., Conclusion: In contrast to Gd-volumes on MRI, changes in (18)F-FET PET may be a valuable parameter to assess treatment response in glioblastoma and to predict survival time.