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Karljosef Langen - One of the best experts on this subject based on the ideXlab platform.
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Comparison of [^18F]Fluoroethyltyrosine PET and Sodium MRI in Cerebral Gliomas: a Pilot Study
Molecular Imaging and Biology, 2020Co-Authors: Aliaksandra Shymanskaya, Karljosef Langen, Gabriele Stoffels, Norbert Galldiks, Philipp Lohmann, Bernd Neumaier, Wieland A. Worthoff, Johannes Lindemeyer, N. Jon ShahAbstract:Purpose Positron emission tomography ( PET) using O-(2-[^18F]fluoroethyl)-L-tyrosine ([^18F]FET) improves the diagnostics of cerebral gliomas compared with conventional magnetic resonance imaging (MRI). Sodium MRI is an evolving method to assess tumor metabolism. In this pilot study, we explored the relationship of [^18F]FET-PET and sodium MRI in patients with cerebral gliomas in relation to the mutational status of the enzyme isocitrate dehydrogenase (IDH). Procedures Ten patients with untreated cerebral gliomas and one patient with a recurrent glioblastoma (GBM) were investigated by dynamic [^18F]FET-PET and sodium MRI using an enhanced simultaneous single-quantum- and triple-quantum-filtered imaging of ^23Na (SISTINA) sequence to estimate total (NaT), weighted non-restricted (NaNR, mainly extracellular), and restricted (NaR, mainly intracellular) sodium in tumors and normal brain tissue. [^18F]FET uptake and sodium parameters in tumors with a different IDH mutational status were compared. After biopsy or resection, histology and the IDH mutational status were determined neuropathologically. Results NaT ( p = 0.05), tumor-to-brain ratios (TBR) of NaT ( p = 0.02), NaNR ( p = 0.003), and the ratio of NaT/NaR ( p
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joint eanm eano rano practice guidelines snmmi procedure standards for imaging of gliomas using pet with radiolabelled amino acids and 18f fdg version 1 0
European Journal of Nuclear Medicine and Molecular Imaging, 2019Co-Authors: Ian Law, Karljosef Langen, Christian La Fougere, Norbert Galldiks, Nathalie L Albert, Javier Arbizu, Ronald Boellaard, Alexander DrzezgaAbstract:These joint practice guidelines, or procedure standards, were developed collaboratively by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the working group for Response Assessment in Neurooncology with PET (PET-RANO). Brain PET imaging is being increasingly used to supplement MRI in the clinical management of glioma. The aim of these standards/guidelines is to assist nuclear medicine practitioners in recommending, performing, interpreting and reporting the results of brain PET imaging in patients with glioma to achieve a high-quality imaging standard for PET using FDG and the radiolabelled amino acids MET, FET and FDOPA. This will help promote the appropriate use of PET imaging and contribute to evidence-based medicine that may improve the diagnostic impact of this technique in neurooncological practice. The present document replaces a former version of the guidelines published in 2006 (Vander Borght et al. Eur J Nucl Med Mol Imaging. 33:1374-80, 2006), and supplements a recent evidence-based recommendation by the PET-RANO working group and EANO on the clinical use of PET imaging in patients with glioma (Albert et al. Neuro Oncol. 18:1199-208, 2016). The information provided should be taken in the context of local conditions and regulations.
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imaging of amino acid transport in brain tumours positron emission tomography with o 2 18f fluoroethyl l tyrosine fet
Methods, 2017Co-Authors: Karljosef Langen, Gabriele Stoffels, Christian Filss, Antje Willuweit, Philipp Lohmann, Bernd Neumaier, Alexander Heinzel, Carina Stegmayr, Felix M MottaghyAbstract: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-[18F]fluoroethyl)-L-tyrosine (FET) which has spread rapidly in the last decade and replaced carbon-11 labelled amino acid tracers such as 11C-methyl-L-methionine (MET) in many centres in Europe. FET can be produced with high efficiency and distributed in a satellite concept like 2-[18F]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.
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the use of amino acid pet and conventional mri for monitoring of brain tumor therapy
NeuroImage: Clinical, 2017Co-Authors: Norbert Galldiks, Ian Law, Whitney B Pope, Javier Arbizu, Karljosef LangenAbstract:Routine diagnostics and treatment monitoring of brain tumors is usually based on contrast-enhanced MRI. However, the capacity of conventional MRI to differentiate tumor tissue from posttherapeutic effects following neurosurgical resection, chemoradiation, alkylating chemotherapy, radiosurgery, and/or immunotherapy may be limited. Metabolic imaging using PET can provide relevant additional information on tumor metabolism, which allows for more accurate diagnostics especially in clinically equivocal situations. This review article focuses predominantly on the amino acid PET tracers 11C-methyl-l-methionine (MET), O-(2-[18F]fluoroethyl)-l-tyrosine (FET) and 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (FDOPA) and summarizes investigations regarding monitoring of brain tumor therapy.
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cost effectiveness analysis of fet pet guided target selection for the diagnosis of gliomas
European Journal of Nuclear Medicine and Molecular Imaging, 2012Co-Authors: Alexander Heinzel, Karljosef Langen, Stephanie Stock, Dirk MullerAbstract:Several diagnostic trials have indicated that the combined use of 18F-fluoroethyl-l-tyrosine (FET) PET and MRI may be superior to MRI alone in selecting the biopsy site for the diagnosis of gliomas. We estimated the cost-effectiveness of the use of amino acid PET compared to MRI alone from the perspective of the German statutory health insurance. To evaluate the incremental cost-effectiveness of the use of amino acid PET, a decision tree model was built. The effectiveness of FET PET was determined by the probability of a correct diagnosis. Costs were estimated for a baseline scenario and for a more expensive scenario in which disease severity was considered. The robustness of the results was tested using deterministic and probabilistic sensitivity analyses. The combined use of PET and MRI resulted in an increase of 18.5% in the likelihood of a correct diagnosis. The incremental cost-effectiveness ratio for one additional correct diagnosis using FET PET was €6,405 for the baseline scenario and €9,114 for the scenario based on higher disease severity. The probabilistic sensitivity analysis confirmed the robustness of the results. The model indicates that the use of amino acid PET may be cost-effective in patients with glioma. As a result of several limitations in the data used for the model, further studies are needed to confirm the results.
Johannes A Hainfellner - One of the best experts on this subject based on the ideXlab platform.
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value of 1h magnetic resonance spectroscopy chemical shift imaging for detection of anaplastic foci in diffusely infiltrating gliomas with non significant contrast enhancement
Journal of Neurology Neurosurgery and Psychiatry, 2011Co-Authors: Georg Widhalm, S Asenbaum, Engelbert Knosp, Martin Krssak, Georgi Minchev, Tatjana Traubweidinger, Thomas Czech, Christine Marosi, Adelheid Wohrer, Johannes A HainfellnerAbstract:Objective In diffusely infiltrating gliomas (DIG), positron emission tomography (PET) imaging is a powerful method for detection of anaplastic foci. Recently, 1 H-magnetic resonance spectroscopy chemical shift imaging (CSI) using choline/creatine (Cho/Cr) or choline/N-acetylaspartate (Cho/NAA) ratios has emerged as a new non-invasive, widely available alternative. The authors therefore correlated CSI with 11 C-methionine (MET)-PET data in a series of DIG with non-significant contrast-enhancement (CE). Methods Thirty-two patients with DIG were examined with single-slice CSI on a 3 T MRI and MET-PET. Maximum pathological intratumoural ratios of CSI (=CSI max ) and maximum tumour-to-normal-brain PET ratios (=PET max ; T/N ratio) were determined. Coregistration of MRI with CSI and PET was performed, and the topographic overlap of CSI max and PET max was analysed. Histological criteria of anaplasia as well as cell proliferation rate were assessed in tumour samples inside and outside CSI max . Results CSI showed a pathological ratio in all patients, whereas PET demonstrated a pathological T/N ratio in 21/32 patients. Topographical correlation of CSI max and PET max revealed a ≥50% overlap in 18/21 and max and Cho/NAA max showed a ≥50% overlap in 24/32 and a max (13.6% vs 6.9%, p Conclusion The results indicate that CSI is a promising method for detection of anaplastic foci within DIG with non-significant CE. Intraoperative use of CSI by multimodal neuronavigation may increase the reliability of detection of malignant areas in glioma surgery and therefore optimise allocation of patients to adjuvant treatments.
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abstract b44 value of 1h magnetic resonance spectroscopy chemical shift imaging csi for detection of anaplastic foci in diffusely infiltrating gliomas with non significant contrast enhancement
Clinical Cancer Research, 2010Co-Authors: Georg Widhalm, S Asenbaum, Engelbert Knosp, Martin Krssak, Georgi Minchev, Adelheid Woehrer, Tatjana Traubweidinger, Thomas Czech, Christine Marosi, Johannes A HainfellnerAbstract:Objective: In diffusely infiltrating gliomas (DIG), positron emission tomography (PET) imaging is a clinically powerful method for detection of anaplastic foci. Recently, 1H-magnetic resonance spectroscopy chemical shift imaging (CSI) using choline/creatine (Cho/Cr) or choline/N-acetylaspartate (Cho/NAA) ratios has emerged as new non-invasive and widely available alternative. We therefore correlated CSI with 11C-methionine (MET)-PET data in a series of DIG with non-significant contrast-enhancement (CE). Methods: Thirty-two patients with DIG were examined with CSI on 3T MRI scanner and MET-PET. Maximum pathologic intratumoral ratios of CSI (=CSImax) and maximum tumor-to-normal-brain PET ratios (=PETmax; T/N ratio) were determined. Co-registration of MRI with CSI and PET was performed and the topographic overlap of CSImax and PETmax was analyzed. Cell proliferation rate in tumor samples inside and outside of CSImax was assessed by MIB-1 labeling index (LI). Results: CSI showed a pathologic ratio in all patients, whereas PET demonstrated a pathologic T/N ratio in 21/32 patients. Topographical correlation of CSImax and PETmax revealed a ≥50% overlap in 18/21 and Conclusion: Our results indicate that CSI is a promising method for detection of anaplastic foci within DIG with non-significant CE. Intraoperative use of CSI by multimodal neuronavigation may increase the reliability of detection of malignant areas in glioma surgery and therefore optimize allocation of patients to adjuvant treatments. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B44
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surgical target selection in cerebral glioma surgery linking methionine met pet image fusion and neuronavigation
Minimally Invasive Neurosurgery, 2007Co-Authors: Karl Roessler, Brigitte Gatterbauer, A Becherer, M Paul, Kurt Kletter, Daniela Prayer, R Hoeftberger, Johannes A Hainfellner, S Asenbaum, Engelbert KnospAbstract:OBJECTIVE: The objective of this study was to investigate the histological correlate of 11 C-methionine (MET) PET uptake of brain gliomas by image fusion for navigated surgery. METHODS: Twenty-seven patients (18 male, 9 female; mean age 42 years; range 11-77 years; 8 low-grade and 11 high-grade astrocytomas or mixed gliomas, 8 oligodendrogliomas) underwent MET PET studies preoperatively. RESULTS: MET PET tumor uptake was detected in 26 of 27 patients (96.3%). The quantitative MET tumor standardized uptake value (SUV) ratio was significantly higher in malignant gliomas and oligodendrogliomas than in low-grade gliomas (2.76/2.62 vs. 1.67, p=0.03). Generally, qualitative visual grading of MET uptake revealed 2 main patterns: focal MET uptake in 12 and uniform global MET uptake in 11 patients. Focal uptake corresponded to malignant glioma histology in 66.7%, and uniform global uptake to oligodendroglial histology in 72.7%. In oligodendrogliomas, global MET uptake constituted 81.5% (range 53.8-135%) of the MRI T 1 tumor volume on average and was limited to the MRI FLAIR tumor volume in 86% (7/8) of patients. Tissue samples of focal MET uptake areas correlated with histological anaplasia in 66.6% (8/12 glioma patients), although 62.5% (5/8 patients) lacked MRI contrast enhancement. CONCLUSION: MET PET image fusion may facilitate the targeting of anaplastic foci in homogeneous MRI non-enhancing gliomas for biopsy, may identify oligodendroglial histology preoperatively as well as characterize biologically active tumor volumes within MRI T 1 /FLAIR tumor areas of candidate patients for resection.
Norbert Galldiks - One of the best experts on this subject based on the ideXlab platform.
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Comparison of [^18F]Fluoroethyltyrosine PET and Sodium MRI in Cerebral Gliomas: a Pilot Study
Molecular Imaging and Biology, 2020Co-Authors: Aliaksandra Shymanskaya, Karljosef Langen, Gabriele Stoffels, Norbert Galldiks, Philipp Lohmann, Bernd Neumaier, Wieland A. Worthoff, Johannes Lindemeyer, N. Jon ShahAbstract:Purpose Positron emission tomography ( PET) using O-(2-[^18F]fluoroethyl)-L-tyrosine ([^18F]FET) improves the diagnostics of cerebral gliomas compared with conventional magnetic resonance imaging (MRI). Sodium MRI is an evolving method to assess tumor metabolism. In this pilot study, we explored the relationship of [^18F]FET-PET and sodium MRI in patients with cerebral gliomas in relation to the mutational status of the enzyme isocitrate dehydrogenase (IDH). Procedures Ten patients with untreated cerebral gliomas and one patient with a recurrent glioblastoma (GBM) were investigated by dynamic [^18F]FET-PET and sodium MRI using an enhanced simultaneous single-quantum- and triple-quantum-filtered imaging of ^23Na (SISTINA) sequence to estimate total (NaT), weighted non-restricted (NaNR, mainly extracellular), and restricted (NaR, mainly intracellular) sodium in tumors and normal brain tissue. [^18F]FET uptake and sodium parameters in tumors with a different IDH mutational status were compared. After biopsy or resection, histology and the IDH mutational status were determined neuropathologically. Results NaT ( p = 0.05), tumor-to-brain ratios (TBR) of NaT ( p = 0.02), NaNR ( p = 0.003), and the ratio of NaT/NaR ( p
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joint eanm eano rano practice guidelines snmmi procedure standards for imaging of gliomas using pet with radiolabelled amino acids and 18f fdg version 1 0
European Journal of Nuclear Medicine and Molecular Imaging, 2019Co-Authors: Ian Law, Karljosef Langen, Christian La Fougere, Norbert Galldiks, Nathalie L Albert, Javier Arbizu, Ronald Boellaard, Alexander DrzezgaAbstract:These joint practice guidelines, or procedure standards, were developed collaboratively by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the working group for Response Assessment in Neurooncology with PET (PET-RANO). Brain PET imaging is being increasingly used to supplement MRI in the clinical management of glioma. The aim of these standards/guidelines is to assist nuclear medicine practitioners in recommending, performing, interpreting and reporting the results of brain PET imaging in patients with glioma to achieve a high-quality imaging standard for PET using FDG and the radiolabelled amino acids MET, FET and FDOPA. This will help promote the appropriate use of PET imaging and contribute to evidence-based medicine that may improve the diagnostic impact of this technique in neurooncological practice. The present document replaces a former version of the guidelines published in 2006 (Vander Borght et al. Eur J Nucl Med Mol Imaging. 33:1374-80, 2006), and supplements a recent evidence-based recommendation by the PET-RANO working group and EANO on the clinical use of PET imaging in patients with glioma (Albert et al. Neuro Oncol. 18:1199-208, 2016). The information provided should be taken in the context of local conditions and regulations.
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the use of amino acid pet and conventional mri for monitoring of brain tumor therapy
NeuroImage: Clinical, 2017Co-Authors: Norbert Galldiks, Ian Law, Whitney B Pope, Javier Arbizu, Karljosef LangenAbstract:Routine diagnostics and treatment monitoring of brain tumors is usually based on contrast-enhanced MRI. However, the capacity of conventional MRI to differentiate tumor tissue from posttherapeutic effects following neurosurgical resection, chemoradiation, alkylating chemotherapy, radiosurgery, and/or immunotherapy may be limited. Metabolic imaging using PET can provide relevant additional information on tumor metabolism, which allows for more accurate diagnostics especially in clinically equivocal situations. This review article focuses predominantly on the amino acid PET tracers 11C-methyl-l-methionine (MET), O-(2-[18F]fluoroethyl)-l-tyrosine (FET) and 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (FDOPA) and summarizes investigations regarding monitoring of brain tumor therapy.
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role of o 2 18f fluoroethyl l tyrosine pet for differentiation of local recurrent brain metastasis from radiation necrosis
The Journal of Nuclear Medicine, 2012Co-Authors: Michael Sabel, Gabriele Stoffels, Norbert Galldiks, Christian Filss, Marc D Piroth, Maximilian I Ruge, Hans Herzog, N J Shah, G R FinkAbstract:The aim of this study was to investigate the potential of O-(2-18F-fluoroethyl)-l-tyrosine (18F-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 18F-FET PET. Maximum and mean tumor-to-brain ratios (TBRmax and TBRmean, respectively; 20–40 min after injection) of 18F-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 18F-FET uptake, (II) 18F-FET uptake peaking early (TTP ≤ 20 min) followed by a plateau, and (III) 18F-FET uptake peaking early (TTP ≤ 20 min) followed by a constant descent. The diagnostic accuracy of the TBRmax and TBRmean of 18F-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 TBRmax and TBRmean were significantly higher in patients with recurrent metastasis (n = 19) than in patients with radiation necrosis (n = 21) (TBRmax, 3.2 ± 0.9 vs. 2.3 ± 0.5, P
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role of o 2 18 f fluoroethyl l tyrosine pet for differentiation of local recurrent brain metastasis from radiation necrosis
The Journal of Nuclear Medicine, 2012Co-Authors: Michael Sabel, Gabriele Stoffels, Norbert Galldiks, Christian Filss, Marc D Piroth, Maximilian I Ruge, Hans Herzog, N J Shah, G R FinkAbstract:The aim of this study was to investigate the potential of O-(2-18F-fluoroethyl)-l-tyrosine (18F-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 18F-FET PET. Maximum and mean tumor-to-brain ratios (TBRmax and TBRmean, respectively; 20–40 min after injection) of 18F-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 18F-FET uptake, (II) 18F-FET uptake peaking early (TTP ≤ 20 min) followed by a plateau, and (III) 18F-FET uptake peaking early (TTP ≤ 20 min) followed by a constant descent. The diagnostic accuracy of the TBRmax and TBRmean of 18F-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 TBRmax and TBRmean were significantly higher in patients with recurrent metastasis (n = 19) than in patients with radiation necrosis (n = 21) (TBRmax, 3.2 ± 0.9 vs. 2.3 ± 0.5, P
Marcus Unterrainer - One of the best experts on this subject based on the ideXlab platform.
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comparison of 18f ge 180 and dynamic 18f fet pet in high grade glioma a double tracer pilot study
European Journal of Nuclear Medicine and Molecular Imaging, 2019Co-Authors: Marcus Unterrainer, D. F. Fleischmann, C. Diekmann, L. Vomacka, S. Lindner, F. Vettermann, M. Brendel, V. WenterAbstract:PET represents a valuable tool for glioma imaging. In addition to amino acid tracers such as 18F-FET, PET targeting the 18-kDa mitochondrial translocator-protein (TSPO) is of high interest for high-grade glioma (HGG) imaging due to its upregulation in HGG cells. 18F-GE-180, a novel TSPO ligand, has shown a high target-to-background contrast in HGG. Therefore, we intra-individually compared its uptake characteristics to dynamic 18F-FET PET and contrast-enhanced MRI in patients with HGG. Twenty HGG patients (nine IDH-wildtype, 11 IDH-mutant) at initial diagnosis (n = 8) or recurrence (n = 12) were consecutively included and underwent 18F-GE-180 PET, dynamic 18F-FET PET, and MRI. The maximal tumour-to-background ratios (TBRmax) and biological tumour volumes (BTV) were evaluated in 18F-GE-180 and 18F-FET PET. Dynamic 18F-FET PET analysis included the evaluation of minimal time-to-peak (TTPmin). In MRI, the volume of contrast-enhancement was delineated (VOLCE). Volumes were spatially correlated using the Sorensen–Dice coefficient. The median TBRmax tended to be higher in 18F-GE-180 PET compared to 18F-FET PET [4.58 (2.33–8.95) vs 3.89 (1.56–7.15); p = 0.062] in the overall group. In subgroup analyses, IDH-wildtype gliomas showed a significantly higher median TBRmax in 18F-GE-180 PET compared to 18F-FET PET [5.45 (2.56–8.95) vs 4.06 (1.56–4.48); p = 0.008]; by contrast, no significant difference was observed in IDH-mutant gliomas [3.97 (2.33–6.81) vs 3.79 (2.01–7.15) p = 1.000]. Only 5/20 cases showed higher TBRmax in 18F-FET PET compared to 18F-GE-180 PET, all of them being IDH-mutant gliomas. No parameter in 18F-GE-180 PET correlated with TTPmin (p > 0.05 each). There was a tendency towards higher median BTVGE-180 [32.1 (0.4–236.0) ml] compared to BTVFET [19.3 (0.7–150.2) ml; p = 0.062] with a moderate spatial overlap [median Sorensen–Dice coefficient 0.55 (0.07–0.85)]. In MRI, median VOLCE [9.7 (0.1–72.5) ml] was significantly smaller than both BTVFET and BTVGE180 (p < 0.001 each), leading to a poor spatial correlation with BTVGE-180 [0.29 (0.01–0.48)] and BTVFET [0.38 (0.01–0.68)]. PET with 18F-GE-180 and 18F-FET provides differing imaging information in HGG dependent on the IDH-mutational status, with diverging spatial overlap and vast exceedance of contrast-enhancement in MRI. Combined PET imaging might reveal new insights regarding non-invasive characterization of tumour heterogeneity and might influence patients’ management.
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serial 18f fet pet imaging of primarily 18f fet negative glioma does it make sense
The Journal of Nuclear Medicine, 2016Co-Authors: Marcus Unterrainer, V. Wenter, Florian Schweisthal, Bogdana Suchorska, Christine Schmidtannwald, Wolfgang P Fendler, Peter Bartenstein, Ulrich Schuller, Jorgchristian Tonn, Nathalie L AlbertAbstract:PET with O-(2-F-18-fluoroethyl)-L-tyrosine (F-18-FET) has gained increasing importance for glioma management. With regard to the occurrence of F-18-FET-negative glioma, we investigated the value of F-18-FET PET monitoring of primarily F-18-FET-negative gliomas concerning the detection of progression and malignant transformation. Methods: We included 31 patients (26 World Health Organization [WHO] grade II, 5 WHO grade III) with primarily F-18-FET-negative glioma and available F-18-FET PET follow-up. F-18-FET PET analysis comprised maximal tumor-to-background ratio (TBRmax) and dynamic analysis of tumoral F-18-FET uptake over time (increasing vs. decreasing) including minimal time to peak (TTPmin). PET findings were correlated with MRI and clinical findings of progression as well as histology of recurrent tumors. Results: Twenty-three of 31 patients experienced tumor progression (median progression-free survival, 41.7 mo). Fourteen of 23 patients showed tumoral F-18-FET uptake concurrent to and 4 of 23 before MRI-derived or clinical signs of tumor progression;2 of 23 patients presented signs of progression in MRI when no concomitant F-18-FET PET was available, but subsequent follow-up PET was positive. In 3 of 23 patients, no F-18-FET uptake was detected at tumor progression. Overall, 20 of 31 primarily F-18-FET-negative glioma turned F-18-FET-positive during the followup. At first occurrence of tumoral F-18-FET uptake, TBRmax was significantly higher in patients with malignant transformation (11/20) than in those without malignant progression (3.2 +/- 0.9 vs. 1.9 +/- 0.5;P = 0.001), resulting in a high detection rate for malignant transformation (for TBRmax. 2.46: sensitivity, 82%;specificity, 89%;negative predictive value, 80%;positive predictive value, 90%;and accuracy, 85%). Although static evaluation was superior to dynamic analysis for the detection of malignant transformation (for TTPmin <= 17.5 min: sensitivity, 73%;specificity, 67%;negative predictive value, 67%;positive predictive value, 73%;and accuracy, 70%), short TTPmin was associated with an early malignant transformation in the further disease course. Overall, 18 of 31 patients experienced malignant transformation;of these, 16 of 17 (94%) evaluable patients showed F-18-FET uptake at the time of malignant transformation. Conclusion: F-18-FET PET monitoring with static and dynamic evaluation is useful even in primarily F-18-FET-negative glioma, providing a high detection rate of both tumor progression and malignant transformation, partly before further signs of progression in MRI. Hence, F-18-FET uptake indicating malignant transformation might influence the patient management.
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serial 18f fet pet of primarily 18f fet negative glioma does it make sense
The Journal of Nuclear Medicine, 2016Co-Authors: Marcus Unterrainer, V. Wenter, Florian Schweisthal, Bogdana Suchorska, Christine Schmidtannwald, Wolfgang P Fendler, Ulrich Scha Ller, Ja Rgchristian Tonn, Peter Bartenstein, Nathalie L AlbertAbstract:183 Objectives 18F-FET PET has gained increasing importance for glioma management. With regard to the occurrence of 18F-FET-negative glioma, we analyzed the value of serial 18F-FET PET of primarily 18F-FET-negative gliomas for the detection of tumor progression. Methods 31 patients with a negative 18F-FET PET at initial diagnosis of a histologically verified glioma (26 WHO grade II, 5 WHO grade III) who had follow-up 18F-FET PET examinations were included. The follow-up 18F-FET PET evaluation comprised a visual analysis (FET-positive vs. FET-negative), assessment of the maximal tumor to background ratio (TBRmax) and a dynamic analysis with evaluation of the minimal time-to-peak (TTPmin). PET findings were compared to clinical and MRI findings of progression as well as histology. Results 23/31 patients experienced tumor progression (median PFS 41.7 months). Of those, 14/23 showed new FET-uptake concurrent to and 4/23 prior to MRI-derived or clinical signs of progression. In 2/23 cases no 18F-FET PET was available at the time of progression, but further scans were 18F-FET-positive. In 3/23 patients no 18F-FET-enhancement was detected at tumor progression. Overall, 20/31 patients turned 18F-FET-positive during the follow-up. At first occurrence of tumoral FET-uptake, TBRmax was significantly higher in glioma with malignant transformation (MT) (11/20) than those without (3.2±0.9 vs. 1.9±0.5; p=0.001), resulting in a high detection rate for MT (for TBRmax>2.46: SN 82%, SP 89%, NPV 80%, PPV 90%, ACC 85%). Although static evaluation was superior to mere dynamic analysis for the detection of MT (for TTPmin≤17.5 min: SN 73%, SP 67%, NPV 67%, PPV 73%, ACC 70%), a dynamic evaluation with TTPmin≤17.5 min was associated with early MT in the course of disease. Conclusions Serial 18F-FET PET is useful even in primarily 18F-FET-negative glioma since it provides a high detection rate of both tumor progression and MT, partially prior to further signs of progression. Consequently, 18F-FET-uptake indicating progression or MT in initially 18F-FET-negative tumors could optimize the patients’ management.
Gabriele Stoffels - One of the best experts on this subject based on the ideXlab platform.
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Comparison of [^18F]Fluoroethyltyrosine PET and Sodium MRI in Cerebral Gliomas: a Pilot Study
Molecular Imaging and Biology, 2020Co-Authors: Aliaksandra Shymanskaya, Karljosef Langen, Gabriele Stoffels, Norbert Galldiks, Philipp Lohmann, Bernd Neumaier, Wieland A. Worthoff, Johannes Lindemeyer, N. Jon ShahAbstract:Purpose Positron emission tomography ( PET) using O-(2-[^18F]fluoroethyl)-L-tyrosine ([^18F]FET) improves the diagnostics of cerebral gliomas compared with conventional magnetic resonance imaging (MRI). Sodium MRI is an evolving method to assess tumor metabolism. In this pilot study, we explored the relationship of [^18F]FET-PET and sodium MRI in patients with cerebral gliomas in relation to the mutational status of the enzyme isocitrate dehydrogenase (IDH). Procedures Ten patients with untreated cerebral gliomas and one patient with a recurrent glioblastoma (GBM) were investigated by dynamic [^18F]FET-PET and sodium MRI using an enhanced simultaneous single-quantum- and triple-quantum-filtered imaging of ^23Na (SISTINA) sequence to estimate total (NaT), weighted non-restricted (NaNR, mainly extracellular), and restricted (NaR, mainly intracellular) sodium in tumors and normal brain tissue. [^18F]FET uptake and sodium parameters in tumors with a different IDH mutational status were compared. After biopsy or resection, histology and the IDH mutational status were determined neuropathologically. Results NaT ( p = 0.05), tumor-to-brain ratios (TBR) of NaT ( p = 0.02), NaNR ( p = 0.003), and the ratio of NaT/NaR ( p
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combined fet pet mri radiomics differentiates radiation injury from recurrent brain metastasis
NeuroImage: Clinical, 2018Co-Authors: Gabriele Stoffels, Maximilian I Ruge, Philipp Lohmann, Martin Kocher, Garry Ceccon, Elena K Bauer, Shivakumar Viswanathan, Bernd Neumaier, Nadim Joni ShahAbstract:Abstract Background The aim of this study was to investigate the potential of combined textural feature analysis of contrast-enhanced MRI (CE-MRI) and static O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for the differentiation between local recurrent brain metastasis and radiation injury since CE-MRI often remains inconclusive. Methods Fifty-two patients with new or progressive contrast-enhancing brain lesions on MRI after radiotherapy (predominantly stereotactic radiosurgery) of brain metastases were additionally investigated using FET PET. Based on histology (n = 19) or clinicoradiological follow-up (n = 33), local recurrent brain metastases were diagnosed in 21 patients (40%) and radiation injury in 31 patients (60%). Forty-two textural features were calculated on both unfiltered and filtered CE-MRI and summed FET PET images (20–40 min p.i.), using the software LIFEx. After feature selection, logistic regression models using a maximum of five features to avoid overfitting were calculated for each imaging modality separately and for the combined FET PET/MRI features. The resulting models were validated using cross-validation. Diagnostic accuracies were calculated for each imaging modality separately as well as for the combined model. Results For the differentiation between radiation injury and recurrence of brain metastasis, textural features extracted from CE-MRI had a diagnostic accuracy of 81% (sensitivity, 67%; specificity, 90%). FET PET textural features revealed a slightly higher diagnostic accuracy of 83% (sensitivity, 88%; specificity, 75%). However, the highest diagnostic accuracy was obtained when combining CE-MRI and FET PET features (accuracy, 89%; sensitivity, 85%; specificity, 96%). Conclusions Our findings suggest that combined FET PET/CE-MRI radiomics using textural feature analysis offers a great potential to contribute significantly to the management of patients with brain metastases.
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imaging of amino acid transport in brain tumours positron emission tomography with o 2 18f fluoroethyl l tyrosine fet
Methods, 2017Co-Authors: Karljosef Langen, Gabriele Stoffels, Christian Filss, Antje Willuweit, Philipp Lohmann, Bernd Neumaier, Alexander Heinzel, Carina Stegmayr, Felix M MottaghyAbstract: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-[18F]fluoroethyl)-L-tyrosine (FET) which has spread rapidly in the last decade and replaced carbon-11 labelled amino acid tracers such as 11C-methyl-L-methionine (MET) in many centres in Europe. FET can be produced with high efficiency and distributed in a satellite concept like 2-[18F]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.
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dynamic o 2 18f fluoroethyl l tyrosine positron emission tomography differentiates brain metastasis recurrence from radiation injury after radiotherapy
Neuro-oncology, 2016Co-Authors: Garry Ceccon, Gabriele Stoffels, Christian Filss, Maximilian I Ruge, Philipp Lohmann, Elena K Bauer, Natalie Judov, Marion Rapp, Christina Hamisch, Martin KocherAbstract:BACKGROUND: The aim of this study was to investigate the potential of dynamic O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-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 (18)F-FET PET. Maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) of (18)F-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 (18)F-FET uptake and the slope of time-activity curves can differentiate local brain metastasis recurrence from radiation-induced changes with high accuracy. (18)F-FET PET may thus contribute significantly to the management of patients with brain metastases.
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role of o 2 18f fluoroethyl l tyrosine pet for differentiation of local recurrent brain metastasis from radiation necrosis
The Journal of Nuclear Medicine, 2012Co-Authors: Michael Sabel, Gabriele Stoffels, Norbert Galldiks, Christian Filss, Marc D Piroth, Maximilian I Ruge, Hans Herzog, N J Shah, G R FinkAbstract:The aim of this study was to investigate the potential of O-(2-18F-fluoroethyl)-l-tyrosine (18F-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 18F-FET PET. Maximum and mean tumor-to-brain ratios (TBRmax and TBRmean, respectively; 20–40 min after injection) of 18F-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 18F-FET uptake, (II) 18F-FET uptake peaking early (TTP ≤ 20 min) followed by a plateau, and (III) 18F-FET uptake peaking early (TTP ≤ 20 min) followed by a constant descent. The diagnostic accuracy of the TBRmax and TBRmean of 18F-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 TBRmax and TBRmean were significantly higher in patients with recurrent metastasis (n = 19) than in patients with radiation necrosis (n = 21) (TBRmax, 3.2 ± 0.9 vs. 2.3 ± 0.5, P