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Simple Summary PET using radiolabelled amino acids has become an essential tool for diagnosing brain tumours in addition to MRI. O-(2-[F-18]fluoroethyl)-L-tyrosine (FET) is one of the most successful tracers in the field. We analysed our database of 6534 FET PET examinations regarding the diagnostic needs and preferences of the referring physicians for FET PET in the clinical decision-making process. The demand for FET PET increased considerably in the last decade, especially for differentiating tumour progress from treatment-related changes in gliomas. Accordingly, referring physicians rated the diagnostics of recurrent glioma and recurrent brain metastases as the most relevant indication for FET PET. The analysis and survey results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for approval for routine use. O-(2-[F-18]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 l

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 timeconsuming 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.

The diagnostic potential of PET using the amino acid analogue O-(2-[F-18]fluoroethyl)-L-tyrosine ([F-18]FET) in brain tumor diagnostics has been proven in many studies during the last two decades and is still the subject of multiple studies every year. In addition to standard magnetic resonance imaging (MRI), positron emission tomography (PET) using [F-18]FET provides important diagnostic data concerning brain tumor delineation, therapy planning, treatment monitoring, and improved differentiation between treatment-related changes and tumor recurrence. The pharmacokinetics, uptake mechanisms and metabolism have been well described in various preclinical studies. The accumulation of [F-18]FET in most benign lesions and healthy brain tissue has been shown to be low, thus providing a high contrast between tumor tissue and benign tissue alterations. Based on logistic advantages of F-18 labelling and convincing clinical results, [F-18]FET has widely replaced short lived amino acid tracers such as L-[C-11]methyl-methionine ([C-11]MET) in many centers across Western Europe. This review summarizes the basic knowledge on [F-18]FET and its contribution to the care of patients with brain tumors. In particular, recent studies about specificity, possible pitfalls, and the utility of [F-18]FET PET in tumor grading and prognostication regarding the revised WHO classification of brain tumors are addressed. (C) 2020 Elsevier Inc. All rights reserved.

PET using O-(2-F-18-fluoroethyl)-L-tyrosine (F-18-FET) is useful to detect residual tumor tissue after glioma resection. Recent animal experiments detected reactive changes in F-18-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 F-18-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 F-18-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 F-18-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 F-18-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 F-18-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 F-18-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 F-18-FET uptake in the flare areas in 4 patients and progress in 1 patient. Conclusion: Our study confirmed that F-18-FET PET provides valuable information for assessing the success of glioma resection. Postoperative reactive changes at the rim of the re

PurposeO-(2-[F-18]fluoroethyl)-l-tyrosine ([F-18]FET) is an established positron emission tomography (PET) tracer for brain tumor imaging. This study explores the influence of dexamethasone therapy on [F-18]FET uptake in the normal brain and its influence on the maximum and mean tumor-to-brain ratio (TBR).Procedures[F-18]FET PET scans of 160 brain tumor patients were evaluated (80 dexamethasone treated, 80 untreated; each group with 40 men/40 women). The standardized uptake value of [F-18]FET uptake in the normal brain (SUVbrain) in the different groups was compared. Nine patients were examined repeatedly with and without dexamethasone therapy.ResultsSUV(brain) of [F-18]FET uptake was significantly higher in dexamethasone-treated patients than in untreated patients (SUVbrain 1.330.1 versus 1.06 +/- 0.16 in male and 1.45 +/- 0.25 versus 1.31 +/- 0.28 in female patients). Similar results were observed in patients with serial PET scans. Furthermore, compared to men, a significantly higher SUVbrain was found in women, both with and without dexamethasone treatment. There were no significant differences between the different groups for TBRmax and TBRmean, which could have been masked by the high standard deviation. In a patient with a stable brain metastasis investigated twice with and without dexamethasone, the TBRmax and the biological tumor volume (BTV) decreased considerably after dexamethasone due to an increased SUVbrain.ConclusionDexamethasone treatment appears to increase the [F-18]FET uptake in the normal brain. An effect on TBRmax, TBRmean, and BTV cannot be excluded which should be considered especially for treatment monitoring and the estimation of BTV using [F-18]FET PET.

Assessment of residual tumor after resection of cerebral gliomas can be difficult with MRI and may be improved by amino acid PET. The aim of this experimental study was to investigate uptake of 2-F-18-fluoroethyl-L-tyrosine (F-18-FET) and L-[methyl-H-3]-methionine (H-3-MET) in residual tumor after surgery and possible false-positive uptake in treatment-related changes. Methods: F98 or GS-9L rat gliomas were implanted into the brain of 64 rats. Tumors were resected after 1 wk of tumor growth, and sham surgery was performed in an additional 10 animals. At different time points after surgery (1, 2, 3, 7, and 14-16 d), rats underwent ex vivo dual-tracer autoradiography using F-18-FET and H-3-MET. Histologic slices were evaluated by immunostaining for cell density and astrogliosis. Tracer uptake was quantified by lesion-to-brain ratios (L/B) at the rim of the resection cavity (considered treatment-related uptake) and in residual or recurrent tumor tissue. Four animals showing no residual tumor underwent PET 3 d after surgery to examine time-activity curves of F-18-FET uptake in treatment-related changes. Results: Treatment-related uptake with a mean L/B of 2.0 +/- 0.3 for F-18-FET and a mean L/B of 1.7 +/- 0.2 for H-3-MET was noted at the rim of the resection cavity in the first week after surgery, decreasing significantly by 14-16 d (P < 0.01). Treatment-related tracer uptake was significantly higher for F-18-FET than for H-3-MET (P< 0.001). Tracer uptake in rat gliomas exceeded treatment-related tracer uptake at all time points (P < 0.001), but the latter was in the range of human gliomas. Reactive astrogliosis was noted near the resection cavity from the second day after surgery. Time-activity curves of F-18-FET uptake in those areas revealed constantly increasing uptake. Conclusion: Surgery may induce significant treatment-related F-18-FET and H-3-MET uptake near the resection cavity in the first week after surgery, presumably caused by reactive astrogliosis. Treatme

PET using the amino-acid O-(2-F-18-fluoroethyl)-L-tyrosine (F-18-FET) is gaining increasing interest for brain tumour management. Semi-quantitative analysis of tracer uptake in brain tumours is based on the standardized uptake value (SUV) and the tumour-to-brain ratio (TBR). The aim of this study was to explore physiological factors that might influence the relationship of SUV of F-18-FET uptake in various brain areas, and thus affect quantification of F-18-FET uptake in brain tumours. Negative F-18-FET PET scans of 107 subjects, showing an inconspicuous brain distribution of F-18-FET, were evaluated retrospectively. Whole-brain quantitative analysis with Statistical Parametric Mapping (SPM) using parametric SUV PET images, and volumes of interest (VOIs) analysis with fronto-parietal, temporal, occipital, and cerebellar SUV background areas were performed to study the effect of age, gender, height, weight, injected activity, body mass index (BMI), and body surface area (BSA). After multivariate analysis, female gender and high BMI were found to be two independent factors associated with increased SUV of F-18-FET uptake in the brain. In women, SUVmean of F-18-FET uptake in the brain was 23% higher than in men (p < 0.01). SUVmean of F-18-FET uptake in the brain was positively correlated with BMI (r = 0.29; p < 0.01). The influence of these factors on SUV of F-18-FET was similar in all brain areas. In conclusion, SUV of F-18-FET in the normal brain is influenced by gender and weakly by BMI, but changes are similar in all brain areas.

Restoration of the blood-brain barrier (BBB) after antiangiogenic therapy of gliomas with bevacizumab may result in a decrease in contrast enhancement on MRI despite tumor progression. This so-called pseudoresponse is difficult to differentiate from a true tumor response with conventional MRI. Initial patient studies have indicated that PET using O-(2-F-18-fluoroethyl)-L-tyrosine (F-18-FET) may be helpful for solving this diagnostic problem. This study was performed to investigate the effects of bevacizumab on BBB permeability and F-18-FET uptake in a human xenograft model. Methods: Human U87 glioblastoma cells were implanted into the striatum of immunodeficient RNU rats. F-18-FET PET scans and ex vivo autoradiography were performed in animals receiving a single high dose of bevacizumab (45 mg/kg 2 d before PET; n = 9) or in animals receiving 2 lower doses (10 mg/kg 9 and 2 d before PET; n = 10) to evaluate short-term and long-term effects on the BBB, respectively, and in control animals without bevacizumab treatment (n = 8). Time-activity curves, slope, and tumor-to-brain ratios of F-18-FET uptake (18-61 min after injection) were evaluated using a volume-of-interest analysis. After PET scanning, Evans blue dye (EBD) was injected into animals, and cryosections of the brains were evaluated by autoradiography, by histology, and for EBD fluorescence to assess BBB permeability. Results: Compared with the control, short-term bevacizumab therapy resulted in a trend toward BBB restoration (P = 0.055) and long-term therapy resulted in a significant decrease (P = 0.004) in BBB permeability, as assessed by EBD fluorescence. In contrast, no significant differences in tumor-to brain ratios or slope of F-18-FET uptake were observed in PET and autoradiography (P > 0.05). Conclusion: F-18-FET uptake in glioblastomas seems to be largely independent of BBB permeability and reflects the viability of tumor tissue during antiangiogenic therapy more reliably than contrast-enhanced MRI.

We investigated the potential of textural feature analysis of O-(2-[F-18]fluoroethyl)-L-tyrosine (F-18-FET) PET to differentiate radiation injury from brain metastasis recurrence. Forty-seven patients with contrast-enhancing brain lesions (n = 54) on MRI after radiotherapy of brain metastases underwent dynamic F-18-FET PET. Tumour-to-brain ratios (TBRs) of F-18-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. Diagnostic accuracy increased from 81 % for TBRmean alone to 85 % when combined with the textural parameter Coarseness or Short-zone emphasis. The accuracy of TBRmax 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 TBRmax. 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 F-18-FET PET scans. aEuro cent Textural feature analysis provides quantitative information about tumour heterogeneity aEuro cent Textural features help improve discrimination between brain metastasis recurrence and radiation injury aEuro cent Textural features might be helpful to further understand tumour heterogeneity aEuro cent Analysis does not require a more time consuming dynamic PET acquisition.

The assessment of cerebral gliomas using magnetic resonance imaging (MRI) provides excellent structural images but cannot solve all diagnostic problems satisfactorily. The differentiation of tumour tissue from non-neoplastic changes may be difficult especially in the post-treatment phase. In recent years, positron emission tomography (PET) using radiolabelled amino acids has gained considerable interest as an additional tool to improve the diagnosis of cerebral gliomas and brain metastases. A key step for this advancement was the development of the F-18 labelled amino acid. O-(2-[F-18]fluoroethyl)-L-tyrosine (FET) which has spread rapidly in the last decade and replaced carbon-11 labelled amino acid tracers such as C-11-methyl-L-methionine (MET) in many centres in Europe. FET can be produced with high efficiency and distributed in a satellite concept like 2-[F-18]fluoro-2-deoxy-D-glucose (FDG). Furthermore, FET exhibits favourable properties such as high in vivo stability, high tumour to background contrast and tissue specific tracer kinetics, which provides additional information for tumour grading or differential diagnosis. The Response Assessment in Neuro-Oncology (RANO) working group - an international effort to develop new standardized response criteria for clinical trials in brain tumours - has recently recommended the additional use of amino acid PET imaging for brain tumour management. FET PET can provide important diagnostic information in crucial situations such as the definition of biopsy site, the delineation of cerebral gliomas for therapy planning, sensitive monitoring of treatment response and an improved differentiation of tumour recurrence from treatment-related changes. In this article the basic information, methodological aspects and the actual status of clinical application of FET PET are reviewed. (C) 2017 Elsevier Inc. All rights reserved.