18f-fluoroethyl-l-tyrosine and Glioma

The aims of the present study were to: 1- critically assess the utility of L-3,4- dihydroxy-6-18Ffluoro-phenyl-alanine (18F-DOPA) and O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) Positron Emission Tomography (PET)/Computed Tomography (CT) in patients with high grade glioma (HGG) and 2- describe the results of 18F-DOPA and 18F-FET PET/CT in a case series of patients with recurrent HGG.. We searched for studies using the following databases: PubMed, Web of Science and Scopus. The search terms were: glioma OR brain neoplasm and DOPA OR DOPA PET OR DOPA PET/CT and FET OR FET PET OR FET PET/CT. From a mono-institutional database, we retrospectively analyzed the 18F-DOPA and 18F-FET PET/CT of 29 patients (age: 56 ± 12 years) with suspicious for recurrent HGG. All patients underwent 18F-DOPA or 18F-FET PET/CT for a multidisciplinary decision. The final definition of recurrence was made by magnetic resonance imaging (MRI) and/or multidisciplinary decision, mainly based on the clinical data.. Fifty-one articles were found, of which 49 were discarded, therefore 2 studies were finally selected. In both the studies, 18F-DOPA and 18F-FET as exchangeable in clinical practice particularly for HGG patients. From our institutional experience, in 29 patients, we found that sensitivity, specificity and accuracy of 18F-DOPA PET/CT in HGG were 100% (95% confidence interval- 95%CI - 81-100%), 63% (95%CI: 39-82%) and 62% (95%CI: 39-81%), respectively. 18F-FET PET/CT was true positive in 4 and true negative in 4 patients. Sensitivity, specificity and accuracy for 18F-FET PET/CT in HGG were 100%.. 18F-DOPA and 18F-FET PET/CT have a similar diagnostic accuracy in patients with recurrent HGG. However, 18F-DOPA PET/CT could be affected by inflammation conditions (false positive) that can alter the final results. Large comparative trials are warranted in order to better understand the utility of 18F-DOPA or 18F-FET PET/CT in patients with HGG.

Topics: Brain Neoplasms; Dihydroxyphenylalanine; Glioma; Humans; Neoplasm Recurrence, Local; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Tyrosine

Gliomas constitute the most frequent primary brain tumors. Glioblastoma, the most common and malignant glioma in adults, has dismal prognosis with any current therapy. On the other hand, low-grade gliomas, the second most common type of gliomas, are potentially curative with appropriate treatment.. We conducted a meta-analysis to assess the performance of PET tracers with the best available evidence, namely, fluorodeoxyglucose (FDG), C-methionine (MET), and F-fluoroethyltyrosine (FET), in differentiating low- from high-grade gliomas.. Twenty-three studies with a total of 994 participants were included in this meta-analysis. The pooled sensitivities of both MET PET and FET PET were found to be significantly higher than of FDG PET (94%, 88%, and 63% respectively, P < 0.001). The pooled specificity of FDG PET was found to be significantly greater compared with both MET PET and FET PET (89%, 55%, and 57%, respectively; P = 0.002). Fluorodeoxyglucose PET was superior in terms of higher positive likelihood ratio values compared with both FET PET and MET PET.. This meta-analysis indicated that both MET and FET were superior to FDG in terms of sensitivity for identifying glioma grade.

Topics: Brain Neoplasms; Carbon Radioisotopes; Fluorodeoxyglucose F18; Glioma; Humans; Methionine; Neoplasm Grading; Positron-Emission Tomography; Tyrosine

Gliomas are the most common primary tumors involving the central nervous system. They can manifest with diverse and non-specific general and neurological symptoms. The diagnostic gold standard is cerebral magnetic resonance imaging and subsequent histological confirmation of the diagnosis. Steroids, especially dexamethasone, are used in case of focal symptoms and of symptoms caused by increased intracranial pressure, and antiepileptic drugs are used to manage epileptic seizures. Non-enzyme-inducing antiepileptic drugs are preferable. Glioma patients have an inherently elevated thromboembolic risk, and therapeutic anticoagulation is indicated following a thromboembolic event. Surgery, radiotherapy and systemic therapy are used as tumor-specific therapy modalities in gliomas. Molecular markers play an increasing role in the prognosis and selection of therapy in daily oncological routine.

Topics: Anticoagulants; Anticonvulsants; Brain Neoplasms; Combined Modality Therapy; Dexamethasone; Diagnosis, Differential; Glioblastoma; Glioma; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Oligodendroglioma; Positron-Emission Tomography; Tyrosine

Brainstem gliomas (BSGs) are uncommon in adults accounting for about 2% of all intracranial neoplasms. They are often phenotypically low-grade as compared to their more common paediatric counterparts. Since brainstem biopsies are rarely performed, these tumours are commonly classified according to their MR imaging characteristics into 4 subgroups: (a) diffuse intrinsic low-grade gliomas, (b) enhancing malignant gliomas, (c) focal tectal gliomas and (d) exophytic gliomas/other subtypes. The prognosis and treatment is variable for the different types and is almost similar to adult supratentorial gliomas. Radiotherapy (RT) with adjuvant chemotherapy is the standard treatment of diffuse low-grade and malignant BSGs, whereas, surgical resection is limited to the exophytic subtypes. Review of previous literature shows that the detailed imaging of adult BSGs has not received significant attention. This review illustrates in detail the imaging features of adult BSGs using conventional and advanced MR techniques like diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), MR perfusion weighted imaging (PWI), MR spectroscopy (MRS), as well as 18F-fluoro-ethyl-tyrosine positron emission tomography (18F-FET/PET). We have discussed the pertinent differences between childhood and adult BSGs, imaging mimics, prognostic factors and briefly reviewed the treatment options of these tumours.

Topics: Adult; Brain Stem; Brain Stem Neoplasms; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Tyrosine

For the past decade, PET with (18)F-fluoro-ethyl-tyrosine ((18)F-FET) has been used in the evaluation of patients with primary brain tumors (PBTs), but so far series have reported only a limited number of patients. The purpose of this systematic review and metaanalysis was to assess the diagnostic performance of (18)F-FET PET in patients with suspicion of PBT.. We examined studies published in the literature using MEDLINE and EMBASE databases. Inclusion criteria were use of (18)F-FET PET for initial assessment of patients with a newly diagnosed brain lesion; patients who had no radiotherapy, surgery, or chemotherapy before (18)F-FET PET; and use of histology as a gold standard. Metaanalysis was performed on a per-patient basis. We secondarily performed receiver-operating-characteristic analysis of pooled patients to determine tumor-to-background ratio (TBR) of (18)F-FET uptake and best diagnostic value.. Thirteen studies totaling 462 patients were included. For the diagnosis of PBT, (18)F-FET PET demonstrated a pooled sensitivity of 0.82 (95% confidence interval [CI], 0.74-0.88), specificity of 0.76 (95% CI, 0.44-0.92), area under the curve of 0.84 (95% CI, 0.80-0.87), positive likelihood ratio of 3.4 (95% CI, 1.2-9.5), and negative likelihood ratio of 0.24 (95% CI, 0.14-0.39). Receiver-operating-characteristic analysis indicated that a mean TBR threshold of at least 1.6 and a maximum TBR of at least 2.1 had the best diagnostic value for differentiating PBTs from nontumoral lesions.. (18)F-FET PET demonstrated excellent performance for diagnosing PBTs. Strict standardization of PET acquisition protocols and prospective, multicenter studies investigating the added value over current MRI are now needed to establish (18)F-FET PET as a highly relevant tool for patient management.

Topics: Animals; Brain Neoplasms; Diagnosis, Differential; Glioma; Humans; Positron-Emission Tomography; Quality Control; Tyrosine

We aimed to elucidate the place of dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) PET in prognostic models of gadolinium (Gd)-negative gliomas.. In 98 patients with Gd-negative gliomas undergoing 18F-FET PET guided biopsy, time activity curves (TACs) of each tumor were qualitatively categorized as either increasing or decreasing. Additionally, post-hoc quantitative analyses were done using minimal time-to-peak (TTPmin) measurements. Prognostic factors were obtained from multivariate hazards models. The fit of the biospecimen- and imaging-derived models was compared.. A homogeneous increasing, mixed, and homogeneous decreasing TAC pattern was seen in 51, 19, and 28 tumors, respectively. Mixed TAC tumors exhibited both increasing and decreasing TACs. Corresponding adjusted 5-year survival was 85%, 47%, and 19%, respectively (P < 0.001). Qualitative and quantitative TAC measurements were highly intercorrelated (P < 0.0001). TTPmin was longest (shortest) in the homogeneous increasing (decreasing) TAC group and in between in the mixed TAC group. TTPmin was longer in isocitrate dehydrogenase (IDH)-mutant tumors (P < 0.001). Outcome was similarly precisely predicted by biospecimen- and imaging-derived models. In the biospecimen model, World Health Organization (WHO) grade (P < 0.0001) and IDH status (P < 0.001) were predictors for survival. Outcome of homogeneous increasing (homogeneous decreasing) TAC tumors was nearly identical, with both TTPmin > 25 min (TTPmin ≤ 12.5 min) tumors and IDH-mutant grade II (IDH-wildtype) gliomas. Outcome of mixed TAC tumors matched that of both intermediate TTPmin (>12.5 min and ≤25 min) and IDH-mutant, grade III gliomas. Each of the 3 prognostic clusters differed significantly from the other ones of the respective models (P < 0.001).. TAC measurements constitute a powerful biomarker independent from tumor grade and IDH status.

Topics: Biomarkers, Tumor; Female; Follow-Up Studies; Gadolinium; Glioma; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Prognosis; Prospective Studies; Survival Rate; Tyrosine

The advantage of combined PET-MRI over sequential PET and MRI is the high spatial conformity and the absence of time delay between the examinations. The benefit of this technique for planning of re-irradiation (re-RT) treatment is unkown yet. Imaging data from a phase 1 trial of re-RT for recurrent glioma was analysed to assess whether planning target volumes and treatment margins in glioma re-RT can be adjusted by PET-MRI with rater independent PET based biological tumour volumes (BTVs).. Combined PET-MRI with the tracer O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) prior to re-RT was performed in recurrent glioma patients in a phase I trial. GTVs including all regions suspicious of tumour on contrast enhanced MRI were delineated by three experienced radiation oncologists and included into MRI based consensus GTVs (MRGTVs). BTVs were semi-automatically delineated with a fixed threshold of 1.6 x background activity. Corresponding BTVs and MRGTVs were fused into union volume PET-MRGTVs. The Sørensen-Dice coefficient and the conformity index were used to assess the geometric overlap of the BTVs with the MRGTVs. A recurrence pattern analysis was performed based on the original planning target volumes (PTVs = GTV + 10 mm margin or 5 mm in one case) and the PET-MRGTVs with margins of 10, 8, 5 and 3 mm.. Seven recurrent glioma patients, who received PET-MRI prior to re-RT, were included into the present planning study. At the time of re-RT, patients were in median 54 years old and had a median Karnofsky Performance Status (KPS) score of 80. Median post-recurrence survival after the beginning of re-RT was 13 months. Concomitant bevacizumab therapy was applied in six patients and one patient received chemoradiation with temozolomide. Median GTV volumes of the three radiation oncologists were 35.0, 37.5 and 40.5 cubic centimeters (cc) and median MRGTV volume 41.8 cc. Median BTV volume was 36.6 cc and median PET-MRGTV volume 59.3 cc. The median Sørensen-Dice coefficient for the comparison between MRGTV and BTV was 0.61 and the median conformity index 0.44. Recurrence pattern analysis revealed two central, two in-field and one distant recurrence within both, the original PTV, as well as the PET-MRGTV with a reduced margin of 3 mm.. PET-MRI provides radiation treatment planning imaging with high spatial and timely conformity for high-grade glioma patients treated with re-RT with potential advancements for target volume delineation. Prospective randomised trials are warranted to further investigate the treatment benefits of PET-MRI based re-RT planning.

Topics: Adolescent; Adult; Aged; Bevacizumab; Brain Neoplasms; Chemoradiotherapy; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Temozolomide; Tumor Burden; Tyrosine

Positron emission tomography (PET) provides quantitative metabolic information and potential biomarkers of treatment outcome. We aimed to determine the prognostic value of early

Topics: Adult; Aged; Brain Neoplasms; Dose-Response Relationship, Radiation; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Prognosis; Prospective Studies; Radiopharmaceuticals; Re-Irradiation; Treatment Outcome; Tumor Burden; Tyrosine

To investigate prospectively the potential of O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) PET in comparison to MRI for the assessment of the response of patients with recurrent high-grade glioma (rHGG) to antiangiogenic treatment.. Ten patients with rHGG were treated biweekly with bevacizumab/irinotecan (BEV/IR). MR images and dynamic (18)F-FET PET scans were obtained at baseline and at follow-up after the start of treatment (median 4.9 weeks). Using MRI treatment response was evaluated according to RANO (Response Assessment in Neuro-Oncology) criteria. For (18)F-FET PET evaluation, a reduction >45 % of the metabolically active tumour volume was considered as a treatment response, with the metabolically active tumour being defined as a tumour-to-brain ratio (TBR) of ≥1.6. The results of the treatment assessments were related to progression-free survival (PFS) and overall survival (OS). For further evaluation of PET data, maximum and mean TBR were calculated using region-of-interest analysis at baseline and at follow-up. Additionally, (18)F-FET uptake kinetic studies were performed at baseline and at follow-up in all patients. Time-activity curves were generated and the times to peak (TTP) uptake (in minutes from the beginning of the dynamic acquisition to the maximum uptake) were calculated.. At follow-up, MRI showed a complete response according to RANO criteria in one of the ten patients (10 %), a partial response in five patients (50 %), and stable disease in four patients (40 %). Thus, MRI did not detect tumour progression. In contrast, (18)F-FET PET revealed six metabolic responders (60 %) and four nonresponders (40 %). In the univariate survival analyses, a response detected by (18)F-FET PET predicted a significantly longer PFS (median PFS, 9 vs. 3 months; P = 0.001) and OS (median OS 23.0 months vs. 3.5 months; P = 0.001). Furthermore, in four patients (40 %), diagnosis according to RANO criteria and by (18)F-FET PET was discordant. In these patients, PET was able to detect tumour progression earlier than MRI (median time benefit 10.5 weeks; range 6-12 weeks). At baseline and at follow-up, in nonresponders TTP was significantly shorter than in responders (baseline TTP 10 ± 8 min vs. 35 ± 9 min; P = 0.002; follow-up TTP 23 ± 9 min vs. 39 ± 8 min; P = 0.02). Additionally, at baseline a kinetic pattern characterized by an early peak of (18)F-FET uptake followed by a constant descent was more frequently observed in the nonresponders (P = 0.018).. Both standard and kinetic imaging parameters derived from(18)F-FET PET seem to predict BEV/IR treatment failure and thus contribute important additional information for clinical management over and above the information obtained by MRI response assessment based on RANO criteria.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Bevacizumab; Brain Neoplasms; Disease-Free Survival; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Treatment Outcome; Tyrosine

The aim of the study was to compare presurgical (18)F-fluoroethyl-L: -tyrosine ((18)F-FET) uptake and Gd-diethylenetriaminepentaacetic acid (DTPA) enhancement on MRI (Gd) with intraoperative 5-aminolevulinic acid (5-ALA) fluorescence in cerebral gliomas.. (18)F-FET positron emission tomography (PET) was performed in 30 patients with brain lesions suggestive of diffuse WHO grade II or III gliomas on MRI. PET and MRI data were coregistered to guide neuronavigated biopsies before resection. After oral application of 5-ALA, 38 neuronavigated biopsies were taken from predefined tumour areas that were positive or negative for (18)F-FET or Gd and checked for 5-ALA fluorescence. (18)F-FET uptake with a mean tumour to brain ratio ≥1.6 was rated as positive.. Of 38 biopsies, 21 corresponded to high-grade glioma tissue (HGG) of WHO grade III (n = 19) or IV (n = 2) and 17 biopsies to low-grade glioma tissue (LGG) of WHO grade II. In biopsies corresponding to HGG, (18)F-FET PET was positive in 86% (18/21), but 5-ALA and Gd in only 57% (12/21). A mismatch between Gd and 5-ALA was observed in 6 of 21 cases of HGG biopsy samples (3 Gd-positive/5-ALA-negative and 3 Gd-negative/5-ALA-positive). In biopsies corresponding to LGG, (18)F-FET was positive in 41% (7/17), while 5-ALA and Gd were negative in all but one instance. All tumour areas with 5-ALA fluorescence were positive on (18)F-FET PET.. There are differences between (18)F-FET and 5-ALA uptake in cerebral gliomas owing to a limited sensitivity of 5-ALA to detect tumour tissue especially in LGG. (18)F-FET PET is more sensitive to detect glioma tissue than 5-ALA fluorescence and should be considered as an additional tool in resection planning.

Topics: Adult; Aged; Aminolevulinic Acid; Blood-Brain Barrier; Brain Neoplasms; Female; Gadolinium DTPA; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Spectrometry, Fluorescence; Tyrosine

5-Aminolevulinic acid (5-ALA) induces fluorescence in high-grade glioma (HGG), which is used for resection. However, the value of 5-ALA-induced fluorescence in low-grade glioma (LGG) is unclear. Time dependency and time kinetics have not yet been investigated. The purpose of this study was to investigate real-time kinetics of protoporphyrin IX (PpIX) in LGG based on hyperspectral fluorescence-based measurements and identify factors that predict fluorescence.. Patients with grade II gliomas and imaging from which HGGs could not be completely ruled out received 5-ALA at 20 mg/kg body weight 4 hours prior to surgery. Fluorescence intensity (FI) and PpIX concentration (CPpIX) were measured in tumor tissue utilizing a hyperspectral camera. Apparent diffusion coefficient (ADC)-based tumor cell density, Ki-67/MIB-1 index, chromosomal 1p/19q codeletion, and 18F-fluoroethyl-l-tyrosine (18F-FET) PET values and their role for predicting fluorescence were evaluated.. Eighty-one biopsies from 25 patients were included. Tissues with fluorescence demonstrated FI and CPpIX maxima between 7 and 8 hours after administration. When visible fluorescence was observed, peaks of FI and CPpIX were observed within this 7- to 8-hour time frame, regardless of any MRI gadolinium contrast enhancement. Gadolinium enhancement (p = 0.008), Ki-67/MIB-1 index (p < 0.001), 18F-FET PET uptake ratio (p = 0.004), and ADC-based tumor cellularity (p = 0.017) significantly differed between fluorescing and nonfluorescing tissue, but not 1p/19q codeletions. Logistic regression demonstrated that 18F-FET PET uptake and Ki-67/MIB-1 index were independently related to fluorescence.. This study reports a fluorescence-based assessment of CPpIX in human LGG tissues related to 18F-FET PET uptake and Ki-67/MIB-1. As in HGGs, fluorescence in LGGs peaked between 7 and 8 hours after 5-ALA application, which has consequences for the timing of administration.

Topics: Adult; Aminolevulinic Acid; Brain Neoplasms; Chromosome Deletion; Female; Fluorescence; Glioma; Humans; Ki-67 Antigen; Magnetic Resonance Imaging; Male; Middle Aged; Photosensitizing Agents; Positron-Emission Tomography; Protoporphyrins; Radiopharmaceuticals; Spectrometry, Fluorescence; Tyrosine

This study aimed to test the diagnostic significance of FET-PET imaging combined with machine learning for the differentiation between multiple sclerosis (MS) and glioma II°-IV°.. Our database was screened for patients in whom FET-PET imaging was performed for the diagnostic workup of newly diagnosed lesions evident on MRI and suggestive of glioma. Among those, we identified patients with histologically confirmed glioma II°-IV°, and those who later turned out to have MS. For each group, tumor-to-brain ratio (TBR) derived features of FET were determined. A support vector machine (SVM) based machine learning algorithm was constructed to enhance classification ability, and Receiver Operating Characteristic (ROC) analysis with area under the curve (AUC) metric served to ascertain model performance.. A total of 41 patients met selection criteria, including seven patients with MS and 34 patients with glioma. TBR values were significantly higher in the glioma group (TBRmax glioma vs. MS: p = 0.002; TBRmean glioma vs. MS: p = 0.014). In a subgroup analysis, TBR values significantly differentiated between MS and glioblastoma (TBRmax glioblastoma vs. MS: p = 0.0003, TBRmean glioblastoma vs. MS: p = 0.0003) and between MS and oligodendroglioma (ODG) (TBRmax ODG vs. MS: p = 0.003; TBRmean ODG vs. MS: p = 0.01). The ability to differentiate between MS and glioma II°-IV° increased from 0.79 using standard TBR analysis to 0.94 using a SVM based machine learning algorithm.. FET-PET imaging may help differentiate MS from glioma II°-IV° and SVM based machine learning approaches can enhance classification performance.

Topics: Adult; Aged; Brain Neoplasms; Female; Glioma; Humans; Image Interpretation, Computer-Assisted; Machine Learning; Male; Middle Aged; Multiple Sclerosis; Positron-Emission Tomography; Radiopharmaceuticals; Tyrosine

O-(2-[F]fluoroethyl)-L-tyrosine positron-emission tomography/computed tomography (F-FET PET/CT) is well known in brain tumor management. Our study aimed to identify the prognostic value of F-FET PET/CT in high-grade gliomas (HGG) according the current 2016 World Health Organization (WHO) classification.Patients with histologically proven WHO 2016 HGG were prospectively included. A dynamic F-FET PET/CT was performed allowing to obtain 2 static PET frames (static frame 1: 20-40 minutes and static frame 2: 2-22 minutes). We analyzed static parameters (standard uptake value [SUV]max, SUVmean, SUVpeak, TBRmax, TBRmean, tumoral lesion glycolysis, and metabolic tumoral volume) for various isocontours (from 10% to 90%). PET parameters, clinical features, and molecular biomarkers were compared with progression-free survival (PFS) and overall survival (OS) in univariate and multivariate analysis.Twenty-nine patients were included (grade III n = 3, grade IV n = 26). Mean PFS and OS were, respectively, 8.8 and 13.9 months. According to univariate analysis, SUVmean, SUVpeak, TBRmax, and TBRmean were significantly correlated with OS. In static 1 analysis, TBRmax seemed to be the best OS prognostic parameter (P = .004). In static 2 analysis, TBRmean was the best parameter (P = .01). In static 1 analysis, only SUVpeak was significant (P = .05) for PFS. Good performance status (PS < 2; P < .0001) and extent of resection (P = .019) identified the subgroup of patients with the best OS. Only TBRmax (P = .026) and extent of resection (P = .025) remained significant parameters in multivariate analysis.Our data suggested that high TBRmax seemed to be the most significant OS independent prognostic factor in patients with newly diagnosed HGG.

Topics: Contrast Media; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Grading; Positron Emission Tomography Computed Tomography; Prognosis; Prospective Studies; Radiopharmaceuticals; Survival Rate; Tyrosine

A 25-year-old man presented with headache and intracranial pressure symptoms. On MRI, an intracranial lesion was detected in the right thalamus with exophytic growth into the third ventricle and inhomogeneous contrast enhancement without necrosis. Dual amino acid (F-FET) and TSPO (F-GE-180) PET imaging showed high tumor-to-background ratios in both scans and a short time-to-peak in F-FET uptake dynamics. Biopsy revealed a diffuse midline glioma, H3K27M-mutant (WHO grade IV), a novel entity in the 2016 WHO classification with poor clinical outcome. Our case shows that the highly aggressive features of this tumor entity can be visualized in vivo by both PET modalities.

Topics: Adult; Biological Transport; Biopsy; Brain Neoplasms; Carbazoles; Glioma; Histones; Humans; Male; Mutation; Positron-Emission Tomography; Tyrosine

Topics: Adult; Area Under Curve; Brain Neoplasms; Central Nervous System Neoplasms; False Positive Reactions; Female; Glioma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Neoplasm Recurrence, Local; Neuroimaging; Positron-Emission Tomography; Retrospective Studies; ROC Curve; Treatment Outcome; Tyrosine

Semiquantitative F-FET PET assessment using the tumor's SUV or tumor-to-background ratios (TBRs) can separate gliomas from peritumoral tissue or progression from pseudoprogression. This study investigated if point spread function (PSF) reconstruction of F-FET PET data affects SUV-based dignity assessment.. This study is a retrospective analysis of 87 glioma patients (female, 36; male, 51; age, 48 [13-81] years) undergoing F-FET PET/MRI for staging (n = 17) or restaging (n = 70). PET was reconstructed using ordered-subset expectation maximization with and without PSF. Lesions were delineated with semiautomated background-adapted thresholding relative to SUVmax; background was delineated contralaterally. Comparative measurements with a National Electrical Manufacturers Association International Electrotechnical Commission PET body phantom (sphere-to-background ratios, 8:1 and 4:1) were performed.. PSF showed significantly higher tumor SUVmax (median difference, +0.1; interquartile range, 0.04-0.18), SUVmean (+0.05; 0.03-0.08), TBRmax|mean (+0.1; 0.04-0.2), and TBRmean|mean (+0.06; 0.03-0.09) than non-PSF (P < 0.001). Background SUVmean was unaffected. In patients and phantom, differences between PSF and non-PSF increased with TBR and decreased with lesion's PET volume. Differences only exceeded 0.2 SUV for SUVmax or 0.1 SUV for SUVmean if TBR was greater than 3 and lesion's PET volume was less than 10 mL (d = 27 mm). Dignity assessment by PSF and non-PSF was concordant in all patients examined for staging (cutoff, TBRmean|mean > 1.6; positive, 14; negative, 3) and restaging (cutoff, TBRmax|mean > 2.0; positive, 67; negative, 3).. PSF increased tumor SUVmax and SUVmean compared with non-PSF F-FET PET/MRI data, especially in small lesions with high TBR (>3). However, dignity assessment using established TBR cutoffs was not affected.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biological Transport; Female; Glioma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Phantoms, Imaging; Positron-Emission Tomography; Retrospective Studies; Tyrosine; Young Adult

A total of 35 treatment-naive patients (mean age, 48 ± 17 years) with histologically proven WHO grade II or III gliomas as defined by the current 2016 WHO classification were included. Static PET/CT imaging was performed 20 min after intravenous [. Fourteen patients presented with grade II (diffuse astrocytoma n = 10, oligodendroglioma n = 4) and 21 patients with grade III glioma (anaplastic astrocytoma n = 15, anaplastic oligodendroglioma n = 6). Twenty-seven out of the 35 patients were PET-positive (grade II n = 8/14, grade III n = 19/21), with grade III tumors exhibiting significantly higher amino acid uptake (TBR

Topics: Brain Neoplasms; Female; Glioma; Humans; Male; Middle Aged; Neoplasm Grading; Positron Emission Tomography Computed Tomography; Prognosis; Progression-Free Survival; Tyrosine; World Health Organization

Following brain cancer treatment, the capacity of anatomical MRI to differentiate neoplastic tissue from treatment-related changes (e.g., pseudoprogression) is limited. This study compared apparent diffusion coefficients (ADC) obtained by diffusion-weighted MRI (DWI) with static and dynamic parameters of O-(2-[. Forty-eight pretreated high-grade glioma patients with anatomical MRI findings suspicious for progression (median time elapsed since last treatment was 16 weeks) were investigated using DWI and dynamic FET PET. Maximum and mean tumour-to-brain ratios (TBR. Data suggest that static and dynamic FET PET provide valuable information concerning the differentiation of early treatment-related changes from tumour progression and outperform ADC measurement for this highly relevant clinical question.

Topics: Adult; Aged; Aged, 80 and over; Diffusion; Diffusion Magnetic Resonance Imaging; Disease Progression; Female; Glioma; Humans; Male; Middle Aged; Positron-Emission Tomography; Survival Analysis; Tyrosine; Young Adult

Patients with high grade glioma (HGG) and contraindications to magnetic resonance imaging (MRI) are dependent on contrast-enhanced computerized tomography (CT) scan imaging for radiation therapy (RT) target volume delineation. This study reviews the experience with the utilization of 18F-fluoroethyl-l-tyrosine positron emission tomography (FET-PET) to define residual disease post craniotomy and optimize RT planning.. Patients with HGG and a contraindication to MRI managed with radiation therapy between 2007 and 2015 were identified. RT target volumes including gross tumour volume (GTV) defined by CT-alone and the biological target volume (BTV) defined by PET-CT were recorded. Clinical target volumes (CTV) were created from the GTV and BTV respectively using standard protocol volume expansion. The expanded BTV was termed clinical target volume biological (CTV-B). Union and intersection between CTV and CTV-B, conformity index, volumetric parameters and individual patient outcomes were analysed.. Six patients fit study criteria. There was a mean increase in CTV-B from CTV by 31.6% with a conformity index of 0.78. Two out of six patients had FET-PET avid disease outside the constructed PTV when delineated by CT-alone. One patient with CT-only planning had a new contrast-enhancing mass within 1 month of completing RT, suggesting potential geographical miss.. Patients with contraindication to MRI the addition of FET-PET can improve target volume delineation for RT Planning.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Brain Neoplasms; Combined Modality Therapy; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy Planning, Computer-Assisted; Treatment Outcome; Tyrosine

The diagnostic accuracy of O-(2-[18F]fluoroethyl)-l-tyrosine (FET) PET scanning in detecting the malignant\ transformation of low-grade gliomas (LGGs) is controversial. In this study, the authors retrospectively assessed the diagnostic potential of FET PET in patients with MRI-suspected malignant progression of LGGs that had previously been treated and the relationship between FET uptake and MRI and molecular biomarkers.. Forty-two patients who had previously undergone surgical or multimodal treatment for a histologically verified\ LGG were referred for FET PET assessment because of clinical signs and/or MRI findings suggestive of tumor progression. Maximal and mean tumor-to-brain ratios (TBRmax and TBRmean, respectively) on FET PET as well as kinetic FET PET parameters (time to peak [TTP] and time-activity curve [TAC]) were determined. Final diagnoses were confirmed histologically. The diagnostic accuracy of FET parameters, separately and combined, for the detection of malignant progression was evaluated using receiver operating characteristic (ROC) curve analysis. Possible predictors that might influence the diagnostic accuracy of FET PET were assessed using multiple linear regression analysis. Spearman’s rank correlation r method was applied to determine the correlation between TBRmax and TAC, and molecular biomarkers from\ tumor tissues.. A total of 47 FET PET scans were obtained and showed no significant association between FET parameters\ and contrast enhancement on MRI. ROC curve analyses overall were unable to demonstrate any significant differentiation between nontransformed LGGs and LGGs that had transformed to high-grade gliomas when evaluating FET parameters separately or combined. After excluding the oligodendroglial subgroup, a significant difference was observed between nontransformed and transformed LGGs when combining FET parameters (i.e., TBRmax > 1.6, TAC describing a plateau or decreasing pattern, and TTP < 25 minutes), with the best result yielded by a combined analysis of TBRmax > 1.6 and TAC with a plateau or decreasing pattern (sensitivity 75% and specificity 83%, p = 0.003). The difference was even greater when patients who had previously undergone oncological treatment were also excluded (sensitivity 93% and specificity 100%, p = 0.001). Multiple linear regression analysis revealed that the presence of an oligodendroglial component (p = 0.029), previous oncological treatment (p = 0.039), and the combined FET parameters (p = 0.027) were\ significant confounding factors in the detection of malignant progression. TBRmax was positively correlated with increasing cell density (p = 0.040) and inversely correlated with IDH1 mutation (p = 0.006).. A single FET PET scan obtained at the time of radiological and/or clinical progression seems to be\ of limited value in distinguishing transformed from nontransformed LGGs, especially if knowledge of the primary tumor histopathology is not known. Therefore, FET PET imaging alone is not adequate to replace histological confirmation, but it may provide valuable information on the location and delineation of active tumor tissue, as well as an assessment of tumor biology in a subgroup of LGGs.

Topics: Adult; Biomarkers, Tumor; Brain Neoplasms; Cell Transformation, Neoplastic; Female; Glioma; Humans; Immunohistochemistry; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Grading; Oligodendroglia; Positron-Emission Tomography; Predictive Value of Tests; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Treatment Outcome; Tyrosine

Amino-acids positron emission tomography (PET) is increasingly used in the diagnostic workup of patients with gliomas, including differential diagnosis, evaluation of tumor extension, treatment planning and follow-up. Recently, progresses of computer vision and machine learning have been translated for medical imaging. Aim was to demonstrate the feasibility of an automated 18F-fluoro-ethyl-tyrosine (18F-FET) PET lesion detection and segmentation relying on a full 3D U-Net Convolutional Neural Network (CNN).. All dynamic 18F-FET PET brain image volumes were temporally realigned to the first dynamic acquisition, coregistered and spatially normalized onto the Montreal Neurological Institute template. Ground truth segmentations were obtained using manual delineation and thresholding (1.3 x background). The volumetric CNN was implemented based on a modified Keras implementation of a U-Net library with 3 layers for the encoding and decoding paths. Dice similarity coefficient (DSC) was used as an accuracy measure of segmentation.. Thirty-seven patients were included (26 [70%] in the training set and 11 [30%] in the validation set). All 11 lesions were accurately detected with no false positive, resulting in a sensitivity and a specificity for the detection at the tumor level of 100%. After 150 epochs, DSC reached 0.7924 in the training set and 0.7911 in the validation set. After morphological dilatation and fixed thresholding of the predicted U-Net mask a substantial improvement of the DSC to 0.8231 (+ 4.1%) was noted. At the voxel level, this segmentation led to a 0.88 sensitivity [95% CI, 87.1 to, 88.2%] a 0.99 specificity [99.9 to 99.9%], a 0.78 positive predictive value: [76.9 to 78.3%], and a 0.99 negative predictive value [99.9 to 99.9%].. With relatively high performance, it was proposed the first full 3D automated procedure for segmentation of 18F-FET PET brain images of patients with different gliomas using a U-Net CNN architecture.

Topics: Glioma; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Neural Networks, Computer; Positron-Emission Tomography; Reproducibility of Results; Sensitivity and Specificity; Tyrosine

Aim was to develop a full automatic clustering approach of the time-activity curves (TAC) from dynamic 18F-FET PET and evaluate its association with IDH1 mutation status and survival in patients with gliomas.. Thirty-seven patients (mean age: 45±13 y) with newly diagnosed gliomas and dynamic 18F-FET PET before any histopathologic investigation or treatment were retrospectively included. Each dynamic 18F-FET PET was realigned to the first image and spatially normalized in the Montreal Neurological Institute template. A tumor mask was semi-automatically generated from Z-score maps. Each brain tumor voxel was clustered in one of the 3 following centroids using dynamic time warping and k-means clustering (centroid #1: slowly increasing slope; centroid #2: rapidly increasing followed by slowly decreasing slope; and centroid #3: rapidly increasing followed by rapidly decreasing slope). The percentage of each dynamic 18F-FET TAC within tumors and other conventional 18F-FET PET parameters (maximum and mean tumor-to-brain ratios [TBRmax and TBRmean], time-to-peak [TTP] and slope) was compared between wild-type and IDH1 mutant tumors. Their prognostic value was assessed in terms of progression free-survival (PFS) and overall survival (OS) by Kaplan-Meier estimates.. Twenty patients were IDH1 wild-type and 17 IDH1 mutant. Higher percentage of centroid #1 and centroid #3 within tumors were positively (P = 0.016) and negatively (P = 0.01) correlated with IDH1 mutated status. Also, TBRmax, TBRmean, TTP, and slope discriminated significantly between tumors with and without IDH1 mutation (P range 0.01 to 0.04). Progression occurred in 22 patients (59%) at a median of 13.1 months (7.6-37.6 months) and 13 patients (35%) died from tumor progression. Patients with a percentage of centroid #1 > 90% had a longer survival compared with those with a percentage of centroid #1 < 90% (P = 0.003 for PFS and P = 0.028 for OS). This remained significant after stratification on IDH1 mutation status (P = 0.029 for PFS and P = 0.034 for OS). Compared to other conventional 18F-FET PET parameters, TTP and slope were associated with PFS and OS (P range 0.009 to 0.04).. Based on dynamic 18F-FET PET acquisition, we developed a full automatic clustering approach of TAC which appears to be a valuable noninvasive diagnostic and prognostic marker in patients with gliomas.

Topics: Adult; Biomarkers, Tumor; Cluster Analysis; Female; Follow-Up Studies; Glioma; Humans; Image Processing, Computer-Assisted; Isocitrate Dehydrogenase; Kaplan-Meier Estimate; Male; Middle Aged; Mutation; Neoplasm Grading; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prognosis; Tyrosine

The extent of surgical resection is significantly correlated with outcome in glioma; however, current intraoperative navigational tools are useful only in a subset of patients. We show here that a new optical intraoperative technique, Cerenkov luminescence imaging (CLI) following intravenous injection of O‑(2-[

Topics: Administration, Intravenous; Animals; Brain Neoplasms; Disease Models, Animal; Glioma; Heterografts; Histocytochemistry; Luminescent Measurements; Neoplasm Transplantation; Rats; Surgery, Computer-Assisted; Treatment Outcome; Tyrosine

We present a 45-year-old man with newly generalized tonic-clonic seizures due to a contrast-enhancing frontal lesion with perifocal edema suggestive for high-grade glioma (HGG). For further evaluation, a dynamic F-FET PET scan was performed, which showed high F-FET-uptake with early peak and constantly decreasing time-activity curves, a characteristic feature of HGG. Stereotactic biopsy and histological evaluation excluded a neoplastic lesion but confirmed a manifestation of neurosarcoidosis with strong expression of the L-amino-acid-transporter considered responsible for F-FET-uptake. Therefore, unknown manifestations of neurosarcoidosis represent a clinical pitfall in F-FET PET and can mimic HGG.

Topics: Brain Neoplasms; Central Nervous System Diseases; Diagnosis, Differential; Glioma; Humans; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Sarcoidosis; Tyrosine

Recent data suggest that diffuse gliomas carrying mutations in codon 34 of the H3 histone family 3A protein represent a very rare, distinct subgroup of IDH-wild type malignant astrocytic gliomas. However, characteristics detectable by MRI and F-FET PET in H3-G34-mutant gliomas are unknown.. We report on MRI and F-FET PET findings in 8 patients from 4 German centers with H3-G34-mutant diffuse gliomas. MRI analyses included multifocality, contrast enhancement, necrosis, cysts, hemorrhages, calcification, and edema. F-FET PET characteristics were evaluated on the basis of static F-FET PET parameters, such as maximal tumor-to-background ratio (TBRmax) and biological tumor volume (BTV), as well as the minimal time-to-peak (TTPmin) obtained from dynamic F-FET PET data.. MRI showed multifocal lesions in 2 of 8, contrast enhancement in 6 of 8, necrosis in 3 of 8, cysts in 3 of 8, hemorrhage in 1 of 8, and calcifications in 1 of 8 patients. None of the tumors showed marked peritumoral edema. However, all 8 H3-G34-mutant gliomas were characterized by a high uptake intensity on F-FET PET with a median TBRmax of 3.4 (range, 2.5-11.7) and a relatively diffuse uptake pattern leading to a large BTV (median, 41.9 mL; range, 7.5-115.6). Dynamic PET data revealed a short median TTPmin of 12.5 minutes.. MRI features of diffuse gliomas with H3-G34 mutation may present very heterogeneously with some cases not even fulfilling the imaging criteria of high-grade glioma. In contrast, in F-FET PET, these tumors show an extensive and diffuse tracer uptake resulting in large BTV with a high TBRmax and a short TTPmin, thus resembling PET characteristics of aggressive high-grade gliomas, namely, glioblastomas.

Topics: Adolescent; Adult; Brain Neoplasms; Child; Female; Glioma; Histones; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; Positron-Emission Tomography; Radiopharmaceuticals; Tyrosine

O-(2-. F98 glioma, 9L gliosarcoma or human U87 glioblastoma cells were implanted into the striatum of 56 Fischer or RNU rats. Thereafter, animals were divided into a control group and a group receiving injections of the glucocorticoid dexamethasone (Dex). After 12-13 days of tumor growth animals received injection of Evans blue dye (EBD) to visualize BBB disturbance and underwent. Despite a considerable reduction of BBB permeability in rat gliomas after Dex treatment, no relevant changes of

Topics: Animals; Antineoplastic Agents, Hormonal; Blood-Brain Barrier; Capillary Permeability; Cell Line, Tumor; Dexamethasone; Glioma; Humans; Male; Radiopharmaceuticals; Rats; Tight Junctions; Tyrosine

Thirty untreated glioma patients (27 high-grade) underwent simultaneous PET/MRI on a 3 T hybrid scanner obtaining structural and dynamic susceptibility contrast sequences. Static FET-uptake and dynamic FET-slope were correlated with rCBV within tumour hotspots across patients and intra-lesionally using a mixed-effects model to account for inter-individual variation. Furthermore, maximal congruency of tumour volumes defined by FET-uptake and rCBV was determined.. While the inter-individual relationship between peak static FET-uptake and rCBV could be confirmed, our intra-lesional, voxel-wise analysis revealed significant positive correlations (median r = 0.374, p < 0.0001). Similarly, significant inter- and intra-individual correlations were observed between FET-slope and rCBV. However, rCBV explained only 12% of the static and 5% of the dynamic FET-PET variance and maximal overlap of respective tumour volumes was 37% on average.. Our results show that the relation between peak values of MR-based rCBV and static FET-uptake can also be observed intra-individually on a voxel basis and also applies to a dynamic FET parameter, possibly determining hotspots of higher biological malignancy. However, just a small part of the FET-PET signal variance is explained by rCBV and tumour volumes determined by the two modalities showed only moderate overlap. These findings indicate that FET-PET and MR-based rCBV provide both congruent and complimentary information on glioma biology.

Topics: Adult; Aged; Brain Neoplasms; Cerebral Angiography; Female; Glioma; Humans; Magnetic Resonance Angiography; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Tyrosine

18F-fluoro-ethyl-tyrosine (FET) is a radiopharmaceutical used in positron emission tomography (PET)-computed tomography in patients with glioma. We propose an original approach combining a radiotracer-pharmacokinetic exploration performed at the voxel level (three-dimensional pixel) and voxel classification to identify tumor tissue. Our methodology was validated using the standard FET-PET approach and magnetic resonance imaging (MRI) data acquired according to the current clinical practices.. FET-PET and MRI data were retrospectively analyzed in ten patients presenting with progressive high-grade glioma. For FET-PET exploration, radioactivity acquisition started 15 min after radiotracer injection, and was measured each 5 min during 40 min. The tissue segmentation relies on population pharmacokinetic modeling with dependent individuals (voxels). This model can be approximated by a linear mixed-effects model. The tumor volumes estimated by our approach were compared with those determined with the current clinical techniques, FET-PET standard approach (i.e., a cumulated value of FET signal is computed during a time interval) and MRI sequences (T1 and T2/fluid-attenuated inversion recovery [FLAIR]), used as references. The T1 sequence is useful to identify highly vascular tumor and necrotic tissues, while the T2/FLAIR sequence is useful to isolate infiltration and edema tissue located around the tumor.. With our kinetic approach, the volumes of tumor tissue were larger than the tissues identified by the standard FET-PET and MRI T1, while they were smaller than those determined with MRI T2/FLAIR.. Our results revealed the presence of suspected tumor voxels not identified by the standard PET approach.

Topics: Aged; Brain Neoplasms; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; Tyrosine

Timely detection of pseudoprogression (PSP) is crucial for the management of patients with high-grade glioma (HGG) but remains difficult. Textural features of O-(2-[18F]fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) mirror tumor uptake heterogeneity; some of them may be associated with tumor progression.. Fourteen patients with HGG and suspected of PSP underwent FET-PET imaging. A set of 19 conventional and textural FET-PET features were evaluated and subjected to unsupervised consensus clustering. The final diagnosis of true progression vs. PSP was based on follow-up MRI using RANO criteria.. Three robust clusters have been identified based on 10 predominantly textural FET-PET features. None of the patients with PSP fell into cluster 2, which was associated with high values for textural FET-PET markers of uptake heterogeneity. Three out of 4 patients with PSP were assigned to cluster 3 that was largely associated with low values of textural FET-PET features. By comparison, tumor-to-normal brain ratio (TNRmax) at the optimal cutoff 2.1 was less predictive of PSP (negative predictive value 57% for detecting true progression, p=0.07 vs. 75% with cluster 3, p=0.04).. Clustering based on textural O-(2-[18F]fluoroethyl)-L-tyrosine PET features may provide valuable information in assessing the elusive phenomenon of pseudoprogression.

Topics: Adult; Aged; Brain Neoplasms; Cluster Analysis; Disease Progression; Disease-Free Survival; Female; Glioma; Humans; Kaplan-Meier Estimate; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Grading; Pilot Projects; Positron Emission Tomography Computed Tomography; Predictive Value of Tests; Radiographic Image Interpretation, Computer-Assisted; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; Time Factors; Treatment Outcome; Tyrosine; Unsupervised Machine Learning

Despite an increasing number of O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET studies in supratentorial gliomas, studies regarding the usefulness of 18F-FET PET in brainstem and spinal cord gliomas to date remain scarce.. Thirty-six 18F-FET PET scans were performed in 29 patients with brainstem (n = 29 scans) or spinal cord glioma (n = 7 scans). In 32 of 36 PET scans, a dynamic acquisition was performed. Fifteen scans in 15 patients were performed to assess newly diagnosed lesions, and 21 scans were obtained during follow-up: for diagnosing tumor progression (n = 15 scans in 14 patients) as well as for treatment monitoring (n = 6 scans in 3 patients). Four patients underwent additional serial scans (range, 1-2), and 3 of these 4 patients were examined for more than one indication. Maximum and mean tumor/brain ratios (TBRmax/mean) of 18F-FET uptake (20-40 min post injection) as well as kinetic 18F-FET uptake parameters were determined. Final diagnoses were confirmed histologically (54%) or by clinical follow-up (46%).. In all newly diagnosed high-grade (n = 3 patients) and in 5 of 11 patients with low-grade gliomas, 18F-FET uptake was increased (TBRmax ≥2.5 and/or TBRmean ≥1.9). In 2 patients with newly diagnosed gliomas without MR contrast enhancement, 18F-FET PET nevertheless showed increased metabolism. At suspected progression, the combination of TBRs with kinetic 18F-FET parameters correctly identified presence or absence of progressive disease in 9 of 11 patients (82%).. This preliminary study suggests that 18F-FET PET adds valuable diagnostic information in brainstem and spinal cord glioma, particularly when the diagnostic information derived from MRI is equivocal.

Topics: Adolescent; Adult; Aged; Brain Stem Neoplasms; Child; Female; Follow-Up Studies; Glioma; Humans; Male; Middle Aged; Neuroimaging; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Spinal Cord Neoplasms; Tyrosine; Young Adult

Dynamic [. The k-means algorithm was applied to dynamic [. The maximum CV of OFVs was 2.7 × 10. From the investigated cluster validity indices, the WB-index is best suited for automated determination of the optimal number of clusters for [

Topics: Algorithms; Brain; Diagnosis, Differential; Glioma; Humans; Image Processing, Computer-Assisted; Positron-Emission Tomography; Recurrence; Reproducibility of Results; Tyrosine

Amino acid positron emission tomography (PET) with [18F]-fluoroethyl-L-tyrosine (FET) is well established in the diagnostic work-up of malignant brain tumors. Analysis of FET-PET data using tumor-to-background ratios (TBR) has been shown to be highly valuable for the detection of viable hypermetabolic brain tumor tissue; however, it has not proven equally useful for tumor grading. Recently, textural features in 18-fluorodeoxyglucose-PET have been proposed as a method to quantify the heterogeneity of glucose metabolism in a variety of tumor entities. Herein we evaluate whether textural FET-PET features are of utility for grading and prognostication in patients with high-grade gliomas.. One hundred thirteen patients (70 men, 43 women) with histologically proven high-grade gliomas were included in this retrospective study. All patients received static FET-PET scans prior to first-line therapy. TBR (max and mean), volumetric parameters and textural parameters based on gray-level neighborhood difference matrices were derived from static FET-PET images. Receiver operating characteristic (ROC) and discriminant function analyses were used to assess the value for tumor grading. Kaplan-Meier curves and univariate and multivariate Cox regression were employed for analysis of progression-free and overall survival.. All FET-PET textural parameters showed the ability to differentiate between World Health Organization (WHO) grade III and IV tumors (p < 0.001; AUC 0.775). Further improvement in discriminatory power was possible through a combination of texture and metabolic tumor volume, classifying 85 % of tumors correctly (AUC 0.830). TBR and volumetric parameters alone were correlated with tumor grade, but showed lower AUC values (0.644 and 0.710, respectively). Furthermore, a correlation of FET-PET texture but not TBR was shown with patient PFS and OS, proving significant in multivariate analysis as well. Volumetric parameters were predictive for OS, but this correlation did not hold in multivariate analysis.. Determination of uptake heterogeneity in pre-therapeutic FET-PET using textural features proved valuable for the (sub-)grading of high-grade glioma as well as prediction of tumor progression and patient survival, and showed improved performance compared to standard parameters such as TBR and tumor volume. Our results underscore the importance of intratumoral heterogeneity in the biology of high-grade glial cell tumors and may contribute to individual therapy planning in the future, although they must be confirmed in prospective studies before incorporation into clinical routine.

Topics: Brain Neoplasms; Female; Glioma; Humans; Male; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Retrospective Studies; Survival Analysis; Tumor Burden; Tyrosine

Both [(18)F]-fluoroethyltyrosine (FET) PET and blood volume (BV) MRI supplement routine T1-weighted contrast-enhanced MRI in gliomas, but whether the two modalities provide identical or complementary information is unresolved. The aims of the study were to investigate the feasibility of simultaneous structural MRI, BV MRI and FET PET of gliomas using an integrated PET/MRI scanner and to assess the spatial and quantitative agreement in tumour imaging between BV MRI and FET PET.. A total of 32 glioma patients underwent a 20-min static simultaneous PET/MRI acquisition on a Siemens mMR system 20 min after injection of 200 MBq FET. The MRI protocol included standard structural MRI and dynamic susceptibility contrast (DSC) imaging for BV measurements. Maximal relative tumour FET uptake (TBRmax) and BV (rBVmax), and Dice coefficients were calculated to assess the quantitative and spatial congruence in the tumour volumes determined by FET PET, BV MRI and contrast-enhanced MRI.. FET volume and TBRmax were higher in BV-positive than in BV-negative scans, and both VOLBV and rBVmax were higher in FET-positive than in FET-negative scans. TBRmax and rBVmax were positively correlated (R (2) = 0.59, p < 0.001). FET and BV positivity were in agreement in only 26 of the 32 patients and in 42 of 63 lesions, and spatial congruence in the tumour volumes as assessed by the Dice coefficients was generally poor with median Dice coefficients exceeding 0.1 in less than half the patients positive on at least one modality for any pair of modalities. In 56 % of the patients susceptibility artefacts in DSC BV maps overlapped the tumour on MRI.. The study demonstrated that although tumour volumes determined by BV MRI and FET PET were quantitatively correlated, their spatial congruence in a mixed population of treated glioma patients was generally poor, and the modalities did not provide the same information in this population of patients. Combined imaging of brain tumour metabolism and perfusion using hybrid PET/MR systems may provide complementary information on tumour biology, but the potential clinical value remains to be determined in future trials.

Topics: Blood Volume; Brain Neoplasms; Feasibility Studies; Glioma; Humans; Magnetic Resonance Imaging; Multimodal Imaging; Positron-Emission Tomography; Retrospective Studies; Time Factors; Tumor Burden; Tyrosine

Current guidelines for glioma imaging by positron emission tomography (PET) using the amino acid analogue O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) recommend image acquisition from 20-40 min post injection (p.i.). The maximal tumour-to-background evaluation (TBRmax) obtained in these summation images does not enable reliable differentiation between low and high grade glioma (LGG and HGG), which, however, can be achieved by dynamic (18)F-FET-PET. We investigated the accuracy of tumour grading using TBRmax values at different earlier time points after tracer injection.. Three hundred and fourteen patients with histologically proven primary diagnosis of glioma (131 LGG, 183 HGG) who had undergone 40-min dynamic (18)F-FET-PET scans were retrospectively evaluated. TBRmax was assessed in the standard 20-40 min summation images, as well as in summation images from 0-10 min, 5-15 min, 5-20 min, and 15-30 min p.i., and kinetic analysis was performed. TBRmax values and kinetic analysis were correlated with histological classification. ROC analyses were performed for each time frame and sensitivity, specificity, and accuracy were assessed.. TBRmax values in the earlier summation images were significantly better for tumour grading (P < 0.001) when compared to standard 20-40 min scans, with best results for the early 5-15 min scan. This was due to higher TBRmax in the HGG (3.9 vs. 3.3; p < 0.001), while TBRmax remained nearly stable in the LGG (2.2 vs. 2.1). Overall, accuracy increased from 70 % in the 20-40 min analysis to 77 % in the 5-15 min images, but did not reach the accuracy of dynamic analysis (80 %).. Early TBRmax assessment (5-15 min p.i.) is more accurate for the differentiation between LGG and HGG than the standard static scan (20-40 min p.i.) mainly caused by the characteristic high (18)F-FET uptake of HGG in the initial phase. Therefore, when dynamic (18)F-FET-PET cannot be performed, early TBRmax assessment can be considered as an alternative for tumour grading.

Topics: Diagnosis, Differential; Female; Glioma; Humans; Kinetics; Male; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Reference Standards; Retrospective Studies; ROC Curve; Tyrosine

PET with O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) has gained increasing importance for glioma management. With regard to the occurrence of (18)F-FET-negative glioma, we investigated the value of (18)F-FET PET monitoring of primarily (18)F-FET-negative gliomas concerning the detection of progression and malignant transformation.. We included 31 patients (26 World Health Organization [WHO] grade II, 5 WHO grade III) with primarily (18)F-FET-negative glioma and available (18)F-FET PET follow-up. (18)F-FET PET analysis comprised maximal tumor-to-background ratio (TBRmax) and dynamic analysis of tumoral (18)F-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.. Twenty-three of 31 patients experienced tumor progression (median progression-free survival, 41.7 mo). Fourteen of 23 patients showed tumoral (18)F-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 (18)F-FET PET was available, but subsequent follow-up PET was positive. In 3 of 23 patients, no (18)F-FET uptake was detected at tumor progression. Overall, 20 of 31 primarily (18)F-FET-negative glioma turned (18)F-FET-positive during the follow-up. At first occurrence of tumoral (18)F-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 (18)F-FET uptake at the time of malignant transformation.. (18)F-FET PET monitoring with static and dynamic evaluation is useful even in primarily (18)F-FET-negative glioma, providing a high detection rate of both tumor progression and malignant transformation, partly before further signs of progression in MRI. Hence, (18)F-FET uptake indicating malignant transformation might influence the patient management.

Topics: Adult; Aged; Brain Neoplasms; Diagnosis, Differential; False Negative Reactions; Female; Glioma; Humans; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Subtraction Technique; Tyrosine; Watchful Waiting; Young Adult

Topics: Brain Neoplasms; Computer Simulation; Glioma; Humans; Image Enhancement; Models, Biological; Neoplasm Grading; Reproducibility of Results; Sensitivity and Specificity; Tyrosine

In suspected grade II gliomas, three distinct patterns of time-activity curves (TAC) on O-(2-[(18)F]fluoroethyl)-1-tyrosine ((18)F-FET) positron emission tomography (PET) have been delineated (i) increasing TAC homogeneously throughout the tumor, and decreasing TAC, (ii) either homogeneously throughout the tumor or (iii) only focally within otherwise increasing TAC patterns. Increasing TAC was associated with low-grade histology and decreasing TAC with high-grade histology. This prospective study analyzed whether these patterns correlate with distinct biological tumor subtypes and differential outcome. (18)F-FET PET-guided biopsies were used for stepwise histopathological evaluation. Molecular-genetic evaluation included O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation, isocitrate dehydrogenase (IDH1/2) mutational and 1p/19q codeletion status. Progression-free survival (PFS) was estimated with the Kaplan-Meier method. Prognostic factors were obtained from multivariate regression models. 98 adult patients were included. Homogeneous increasing, focal decreasing and homogeneous decreasing TAC were seen in 51, 19 and 28 patients. The corresponding 1-year (2-years) PFS were 92% (85%), 89% (51%) and 50% (28%; p = 0.002). IDH1/2 mutations were more frequent in tumors with homogeneous increasing (90%) and focal decreasing (79%) TAC, but were rare in those exhibiting homogeneous decreasing TAC (25%; p < 0.001). Overall, TAC patterns, IDH1/2 mutational and 1p/19q codeletion status were powerful and independent prognostic factors. Dynamic (18)F-FET PET might be an important and independent imaging biomarker for patients with suspected WHO grade II gliomas and offers perspectives for stratified diagnostic and therapeutic strategies. Tumors with focal decreasing TAC need highly targeted surgical interventions to avoid undergrading and undertreatment.

Topics: Adult; Aged; Aged, 80 and over; Disease-Free Survival; Female; Glioma; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; O(6)-Methylguanine-DNA Methyltransferase; Positron-Emission Tomography; Prognosis; Promoter Regions, Genetic; Prospective Studies; Radiopharmaceuticals; Tyrosine; Young Adult

Because the clinical course of low-grade gliomas in the individual adult patient varies considerably and is unpredictable, we investigated the prognostic value of dynamic (18)F-fluorethyltyrosine ((18)F-FET) PET in the early diagnosis of astrocytic low-grade glioma (World Health Organization grade II).. Fifty-nine patients with newly diagnosed low-grade glioma and dynamic (18)F-FET PET before histopathologic assessment were retrospectively investigated. (18)F-FET PET analysis comprised a qualitative visual classification of lesions; assessment of the semiquantitative parameters maximal, mean, and total standardized uptake value as ratio to background and biologic tumor volume; and dynamic analysis of intratumoral (18)F-FET uptake over time (increasing vs. decreasing time-activity curves). The correlation between PET parameters and progression-free survival, overall survival, and time to malignant transformation was investigated.. (18)F-FET uptake greater than the background level was found in 34 of 59 tumors. Dynamic (18)F-FET uptake analysis was available for 30 of these 34 patients. Increasing and decreasing time-activity curves were found in 18 and 12 patients, respectively. Neither the qualitative factor presence or absence of (18)F-FET uptake nor any of the semiquantitative uptake parameters significantly influenced clinical outcome. In contrast, decreasing time-activity curves in the kinetic analysis were highly prognostic for shorter progression-free survival and time to malignant transformation (P < 0.001).. Absence of (18)F-FET uptake in newly diagnosed astrocytic low-grade glioma does not generally indicate an indolent disease course. Among the (18)F-FET-positive gliomas, decreasing time-activity curves in dynamic (18)F-FET PET constitute an unfavorable prognostic factor in astrocytic low-grade glioma and, by identifying high-risk patients, may ease treatment decisions.

Topics: Adult; Astrocytes; Brain Neoplasms; Disease Progression; Disease-Free Survival; Female; Glioma; Humans; Male; Middle Aged; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Retrospective Studies; Risk; Time Factors; Treatment Outcome; Tyrosine

Concerning the preoperative clinical diagnostic work-up of glioma patients, tumor heterogeneity challenges the oncological therapy. The current study assesses the performance of a multimodal imaging approach to differentiate between areas in malignant gliomas and to investigate the extent to which such a combinatorial imaging approach might predict the underlying histology.. Prior to surgical resection, patients harboring intracranial gliomas underwent MRIs (MR-S, PWI) and (18)F-FET-PETs. Intratumoral and peritumoral biopsy targets were defined, by MRI only, by FET-PET only, and by MRI and FET-PET combined, and biopsied prior to surgical resection and which then received separate histopathological examinations.. In total, 38 tissue samples were acquired (seven glioblastomas, one anaplastic astrocytoma, one anaplastic oligoastrocytoma, one diffuse astrocytoma, and one oligoastrocytoma) and underwent histopathological analysis. The highest mean values of Mib1 and CD31 were found in the target point "T' defined by MRI and FET-PET combined. A significant correlation between NAA/Cr and PET tracer uptake (-0.845, p<0.05) as well as Cho/Cr ratio and cell density (0.742, p<0.05) and NAA/Cr ratio and MIB-1 (-0761, p<0.05) was disclosed for this target point, though not for target points defined by MRI and FET-PET alone.. Multimodal-imaging-guided stereotactic biopsy correlated more with histological malignancy indices, such as cell density and MIB-1 labeling, than targets that were based solely on the highest amino acid uptake or contrast enhancement on MRI. The results of our study indicate that a combined PET-MR multimodal imaging approach bears potential benefits in detecting glioma heterogeneity.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Brain Neoplasms; Diagnosis, Differential; Female; Glioma; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tyrosine; Young Adult

MRI and PET with 18F-fluoro-ethyl-tyrosine (FET) have been increasingly used to evaluate patients with gliomas. Our purpose was to assess the additive value of MR spectroscopy (MRS), diffusion imaging and dynamic FET-PET for glioma grading.. 38 patients (42 ± 15 aged, F/M: 0.46) with untreated histologically proven brain gliomas were included. All underwent conventional MRI, MRS, diffusion sequences, and FET-PET within 3±4 weeks. Performances of tumour FET time-activity-curve, early-to-middle SUVmax ratio, choline / creatine ratio and ADC histogram distribution pattern for gliomas grading were assessed, as compared to histology. Combination of these parameters and respective odds were also evaluated.. Tumour time-activity-curve reached the best accuracy (67%) when taken alone to distinguish between low and high-grade gliomas, followed by ADC histogram analysis (65%). Combination of time-activity-curve and ADC histogram analysis improved the sensitivity from 67% to 86% and the specificity from 63-67% to 100% (p < 0.008). On multivariate logistic regression analysis, negative slope of the tumour FET time-activity-curve however remains the best predictor of high-grade glioma (odds 7.6, SE 6.8, p = 0.022).. Combination of dynamic FET-PET and diffusion MRI reached good performance for gliomas grading. The use of FET-PET/MR may be highly relevant in the initial assessment of primary brain tumours.

Topics: Adult; Brain Neoplasms; Female; Glioma; Humans; Image Enhancement; Magnetic Resonance Imaging; Male; Multimodal Imaging; Neoplasm Grading; Observer Variation; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tyrosine

Inter- and intratumor heterogeneity and the variable course of disease in patients with glioma motivate the investigation of new prognostic factors to optimize individual treatment. Here we explore the usefulness of standard static and more sophisticated dynamic (18)F-fluoroethyltyrosine-PET imaging for the assessment of patient prognosis.. Thirty-four consecutive patients with untreated, first-diagnosed, histologically proved glioma were included in this retrospective study. All patients underwent dynamic PET scans before surgery (± standard treatment) and were followed up clinically and by MR imaging. Static and dynamic tumor-to-background ratio, TTP, and slope-to-peak were obtained and correlated with progression-free survival.. Twenty of 34 patients experienced progression, with a median progression-free survival of 28.0 ± 11.1 months. Dynamic TTP was highly prognostic for recurrent disease, showing a strong correlation with progression-free survival (hazard ratio, 6.050; 95% CI, 2.11-17.37; P < .001). Most interesting, this correlation also proved significant in the subgroup of low-grade glioma (hazard ratio, 5.347; 95% CI, 1.05-27.20; P = .044), but not when using established static imaging parameters, such as maximum tumor-to-background ratio and mean tumor-to-background ratio. In the high-grade glioma subgroup, both dynamic and static parameters correlated with progression-free survival. The best results were achieved by defining ROIs around "hot spots" in earlier timeframes, underlining the concept of intratumor heterogeneity.. (18)F-fluoroethyltyrosine-PET can predict recurrence in patients with glioma, with dynamic analysis showing advantages over static imaging, especially in the low-grade subgroup.

Topics: Adult; Aged; Brain Neoplasms; Disease Progression; Disease-Free Survival; Female; Glioma; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Prognosis; Retrospective Studies; Tyrosine

High-grade gliomas (HGGs) are the most common malignant primary tumors of the central nervous system. PET probes of amino acid transport such as O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET), 3,4-dihydroxy-6-(18)F-fluoro-l-phenylalanine ((18)F-DOPA), and (11)C-methionine ((11)C-MET) detect primary and recurrent tumors with a high accuracy. (18)F-FET is predominantly used in Europe, whereas amino acid transport imaging is infrequently done in the United States. The aim of this study was to determine whether (18)F-FET and (18)F-DOPA PET/CT provide comparable information in HGG.. Thirty (18)F-FET and (18)F-DOPA PET/CT scans were obtained before surgery or biopsy in 27 patients with high clinical suspicion for primary or recurrent HGG (5 primary, 22 recurrent tumors). (18)F-FET and (18)F-DOPA PET/CT images were compared visually and semiquantitatively (maximum standardized uptake value [SUV(max)], mean SUV [SUV(mean)]). Background (SUV(max) and SUV(mean)) and tumor-to-background ratios (TBRs) were calculated for both PET probes. The degree of (18)F-DOPA uptake in the basal ganglia (SUV(mean)) was also assessed.. Visual analysis revealed no difference in tumor uptake pattern between the 2 PET probes. The SUV(mean) and SUV(max) for (18)F-FET were higher than those of (18)F-DOPA (4.0 ± 2.0 and 4.9 ± 2.3 vs. 3.5 ± 1.6 and 4.3 ± 2.0, respectively; all P < 0.001). TBRs for SUV(mean) but not for SUV(max) were significantly higher for (18)F-FET than (18)F-DOPA (TBR SUV(mean): 3.8 ± 1.7 vs. 3.4 ± 1.2, P = 0.004; TBR SUV(max): 3.3 ± 1.6 and 3.0 ± 1.1, respectively; P = 0.086). (18)F-DOPA uptake by the basal ganglia was present (SUV(mean), 2.6 ± 0.7) but did not affect tumor visualization.. Whereas visual analysis revealed no significant differences in uptake pattern for (18)F-FET and (18)F-DOPA in patients with primary or recurrent HGG, both SUVs and TBRs for SUV(mean) were significantly higher for (18)F-FET. However, regarding tumor delineation, both tracers performed equally well and seem equally feasible for imaging of primary and recurrent HGG. These findings suggest that both PET probes can be used based on availability in multicenter trials.

Topics: Adult; Aged; Aged, 80 and over; Amino Acids; Basal Ganglia; Biopsy; Brain; Brain Neoplasms; Dihydroxyphenylalanine; Female; Glioma; Humans; Logistic Models; Male; Middle Aged; Prospective Studies; Radionuclide Imaging; Recurrence; Tyrosine

The goal of this study was to evaluate the (18)F-labeled nonnatural amino acid (S)-2-amino-3-[1-(2-(18)F-fluoroethyl)-1H-[1,2,3]triazol-4-yl]propanoic acid ((18)F-AFETP) as a PET imaging agent for brain tumors and to compare its effectiveness with the more-established tracers O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) and (18)F-FDG in a murine model of glioblastoma. The tracer (18)F-AFETP is a structural analog of histidine and is a lead compound for imaging cationic amino acid transport, a relatively unexplored target for oncologic imaging.. (18)F-AFETP was prepared using the click reaction. BALB/c mice with intracranially implanted delayed brain tumor (DBT) gliomas (n = 4) underwent biodistribution and dynamic small-animal PET imaging for 60 min after intravenous injection of (18)F-AFETP. Tumor and brain uptake of (18)F-AFETP were compared with those of (18)F-FDG and (18)F-FET through small-animal PET analyses.. (18)F-AFETP demonstrated focally increased uptake in tumors with good visualization. Peak tumor uptake occurred within 10 min of injection, with stable or gradual decrease over time. All 3 tracers demonstrated relatively high uptake in the DBTs throughout the study. At late time points (47.5-57.5 min after injection), the average standardized uptake value with (18)F-FDG (1.9 ± 0.1) was significantly greater than with (18)F-FET (1.1 ± 0.1) and (18)F-AFETP (0.7 ± 0.2). The uptake also differed substantially in normal brain, with significant differences in the standardized uptake values at late times among (18)F-FDG (1.5 ± 0.2), (18)F-FET (0.5 ± 0.05), and (18)F-AFETP (0.1 ± 0.04). The resulting average tumor-to-brain ratio at the late time points was significantly higher for (18)F-AFETP (7.5 ± 0.1) than for (18)F-FDG (1.3 ± 0.1) and (18)F-FET (2.0 ± 0.3).. (18)F-AFETP is a promising brain tumor imaging agent, providing rapid and persistent tumor visualization, with good tumor-to-normal-brain ratios in the DBT glioma model. High tumor-to-brain, tumor-to-muscle, and tumor-to-blood ratios were observed at 30 and 60 min after injection, with higher tumor-to-brain ratios than obtained with (18)F-FET or (18)F-FDG. These results support further development and evaluation of (18)F-AFETP and its derivatives for tumor imaging.

Topics: Alanine; Animals; Brain Neoplasms; Cell Line, Tumor; Fluorodeoxyglucose F18; Glioma; Male; Metabolic Clearance Rate; Mice; Mice, Inbred BALB C; Organ Specificity; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tissue Distribution; Triazoles; Tyrosine

To date, the use of structural MR imaging (including contrast-enhanced and T2-weighted or fluid-attenuated inversion recovery-weighted images) is the standard method to diagnose tumor progression and to assess antiangiogenic treatment effects. However, several studies have suggested that O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET adds valuable clinical information to the information derived from structural MR imaging alone. We evaluated the effectiveness and cost-effectiveness of the addition of (18)F-FET PET to structural MR imaging for the management of treatment with bevacizumab and irinotecan (BEV/IR) in patients with recurrent high-grade glioma compared with MR imaging alone from the perspective of the German Statutory Health Insurance.. To evaluate the incremental cost-effectiveness of the additional use of (18)F-FET PET, a decision tree model was used. Effectiveness of (18)F-FET PET was defined as correct identification of both tumor progression before BEV/IR treatment initiation and BEV/IR treatment response and was evaluated for the combination of (18)F-FET PET and MR imaging compared with MR imaging alone. Costs were estimated for a baseline scenario and for a more expensive scenario. The robustness of the results was tested using deterministic and probabilistic sensitivity analyses.. The use of (18)F-FET PET resulted in a number needed to diagnose of 2.4, that is, 3 additional patients have to be diagnosed to avoid 1 wrong diagnosis. The incremental cost-effectiveness ratio of (18)F-FET PET/MR imaging compared with MR imaging alone was €5,725 (€1 ≈ $1.30) for the baseline scenario and €8,145 for the more expensive scenario per additional correct diagnosis. The probabilistic sensitivity analysis confirmed the robustness of the results.. The model suggests that the additional use of (18)F-FET PET in the management of patients with recurrent high-grade glioma treated with BEV/IR may be cost-effective. Integration of (18)F-FET PET has the potential to avoid overtreatment and corresponding costs, as well as unnecessary side effects to the patient.

Topics: Antibodies, Monoclonal, Humanized; Bevacizumab; Brain Neoplasms; Camptothecin; Cost-Benefit Analysis; Decision Trees; Disease-Free Survival; Glioma; Humans; Irinotecan; Magnetic Resonance Imaging; Monte Carlo Method; Neoplasm Grading; Positron-Emission Tomography; Recurrence; Treatment Outcome; Tyrosine

The aim of this study was to assess the clinical value of O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) PET in the initial diagnosis of cerebral lesions suggestive of glioma.. In a retrospective study, we analyzed the clinical, radiologic, and neuropathologic data of 174 patients (77 women and 97 men; mean age, 45 ± 15 y) who had been referred for neurosurgical assessment of unclear brain lesions and had undergone (18)F-FET PET. Initial histology (n = 168, confirmed after surgery or biopsy) and the clinical course and follow-up MR imaging in 2 patients revealed 66 high-grade gliomas (HGG), 77 low-grade gliomas (LGG), 2 lymphomas, and 25 nonneoplastic lesions (NNL). In a further 4 patients, initial histology was unspecific, but during the course of the disease all patients developed an HGG. The diagnostic value of maximum and mean tumor-to-brain ratios (TBR(max/)TBR(mean)) of (18)F-FET uptake was assessed using receiver-operating-characteristic (ROC) curve analyses to differentiate between neoplastic lesions and NNL, between HGG and LGG, and between high-grade tumor (HGG or lymphoma) and LGG or NNL.. Neoplastic lesions showed significantly higher (18)F-FET uptake than NNL (TBR(max), 3.0 ± 1.3 vs. 1.8 ± 0.5; P < 0.001). ROC analysis yielded an optimal cutoff of 2.5 for TBR(max) to differentiate between neoplastic lesions and NNLs (sensitivity, 57%; specificity, 92%; accuracy, 62%; area under the curve [AUC], 0.76; 95% confidence interval [CI], 0.68-0.84). The positive predictive value (PPV) was 98%, and the negative predictive value (NPV) was 27%. ROC analysis for differentiation between HGG and LGG (TBR(max), 3.6 ± 1.4 vs. 2.4 ± 1.0; P < 0.001) yielded an optimal cutoff of 2.5 for TBR(max) (sensitivity, 80%; specificity, 65%; accuracy, 72%; AUC, 0.77; PPV, 66%; NPV, 79%; 95% CI, 0.68-0.84). Best differentiation between high-grade tumors (HGG or lymphoma) and both NNL and LGG was achieved with a TBR(max) cutoff of 2.5 (sensitivity, 79%; specificity, 72%; accuracy, 75%; AUC, 0.79; PPV, 65%; NPV, 84%; 95% CI, 0.71-0.86). The results for TBR(mean) were similar with a cutoff of 1.9.. (18)F-FET uptake ratios provide valuable additional information for the differentiation of cerebral lesions and the grading of gliomas. TBR(max) of (18)F-FET uptake beyond the threshold of 2.5 has a high PPV for detection of a neoplastic lesion and supports the necessity of an invasive procedure, for example, biopsy or surgical resection. Low (18)F-FET uptake (TBR(max) < 2.5) excludes a high-grade tumor with high probability.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Area Under Curve; Brain Neoplasms; Child; Child, Preschool; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Tyrosine

Positron emission tomography (PET) with radiolabeled amino acids provides information on biopsy target and chemotherapy response in patients with low-grade gliomas (LGG). In this article, we addressed whether PET with F-18 choline (CHO) detects increased metabolism in F-18 fluoroethyltyrosine (FET)-negative LGG patients.. Six LGG patients with nongadolinium-enhancing (magnetic resonance) FET-negative LGG were imaged with CHO PET. Regions of interest were positioned over tumor and contralateral brain. Uptake of FET and CHO was quantified as count ratio of tumor to contralateral brain.. The mean FET uptake ratio for FET-negative LGG was 0.95 ± 0.03 (mean ± standard deviation). Five tumors did not show increased uptake ratios for CHO (0.96 ± 0.12). Slightly increased CHO uptake was found in 1 patient (1.24), which, however, was not associated with tumor visualization.. Amino acid and choline uptake appear to behave similar in nongadolinium-enhancing LGG. For clinical purposes, CHO PET is not superior to FET PET.

Topics: Adult; Brain Neoplasms; Choline; False Negative Reactions; Female; Glioma; Humans; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tyrosine

Several diagnostic trials have indicated that the combined use of (18)F-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.

Topics: Biopsy; Brain Neoplasms; Cost-Benefit Analysis; Decision Trees; Glioma; Humans; Magnetic Resonance Imaging; Monte Carlo Method; Positron-Emission Tomography; Radiopharmaceuticals; Tyrosine

Since differentiation between low-grade glioma (LGG) and high-grade glioma (HGG) remains challenging according to MRI criteria alone, we investigated the discriminative value of additional dynamic FET PET in patients with MRI-suspected LGG.. Included in this retrospective study were 127 patients with newly diagnosed MRI-suspected LGG and dynamic FET PET prior to histopathological assessment. FET PET lesions were visually classified as having reduced, normal, or increased tracer uptake. Maximal tumour uptake scaled to the mean background uptake (SUV(max)/BG), mean tumour uptake (SUV(mean)/BG), biological tumour volume and kinetics were evaluated and correlated with individual histopathological findings.. Histopathological analysis revealed 71 patients with LGG, 47 patients with HGG (including 5 glioblastoma multiforme), 2 patients with low-grade ganglioglioma and 7 patients with non-neoplastic lesions. Of the 127 patients, 97 had lesions with increased FET uptake, of which 93 were neoplastic. Increased uptake was found in 49/71 LGG (69 %) and 42/47 HGG (89 %). None of the conventional uptake parameters differed significantly between the HGG and LGG groups. Kinetic analysis reliably identified HGG (sensitivity 95 %, specificity 72 %, PPV 74 %, NPV 95 %). Normal tracer uptake was observed in 19 patients (15 with LGG, 1 with HGG and 3 with non-neoplastic lesions) and reduced uptake in 11 patients (7 with LGG and 4 with HGG).. Among the MRI-suspected LGG, kinetic but not conventional analysis of FET uptake enabled remarkably high sensitivity for detection of HGG. This held true even for lesions with low or diffuse tracer uptake. Lesions with reduced tracer uptake must be interpreted with caution, as they can also harbour HGG tissue.

Topics: Biological Transport; Cohort Studies; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Reproducibility of Results; Retrospective Studies; Tyrosine

Molecular imaging studies have recently found inter- and intratumoral heterogeneity in World Health Organization (WHO) grade II gliomas. A correlative analysis with tumor histology, however, is still lacking. For elucidation we conducted the current prospective study. Fifty-five adult patients with an MRI-based suspicion of a WHO grade II glioma were included. [F-18]Fluoroethyltyrosine ((18)FET) uptake kinetic studies were combined with frame-based stereotactic localization techniques and used as a guide for stepwise (1-mm steps) histopathological evaluation throughout the tumor space. In tumors with heterogeneous PET findings, the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and expression of mutated protein isocitrate dehydrogenase variant R132H (IDH1) were determined inside and outside of hot spot volumes. Metabolic imaging revealed 3 subgroups: the homogeneous WHO grade II glioma group (30 patients), the homogeneous malignant glioma group (10 patients), and the heterogeneous group exhibiting both low- and high-grade characteristics at different sites (15 patients). Stepwise evaluation of 373 biopsy samples indicated a strong correlation with analyses of uptake kinetics (p < 0.0001). A homogeneous pattern of uptake kinetics was linked to homogeneous histopathological findings, whereas a heterogeneous pattern was associated with histopathological heterogeneity; hot spots exhibiting malignant glioma characteristics covered 4-44% of the entire tumor volumes. Both MGMT and IDH1 status were identical at different tumor sites and not influenced by heterogeneity. Maps of (18)FET uptake kinetics strongly correlated with histopathology in suspected grade II gliomas. Anaplastic foci can be accurately identified, and this finding has implications for prognostic evaluation and treatment planning.

Topics: Adolescent; Adult; Aged; Brain Neoplasms; DNA Methylation; Female; Glioma; Humans; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Male; Middle Aged; O(6)-Methylguanine-DNA Methyltransferase; Positron-Emission Tomography; Promoter Regions, Genetic; Prospective Studies; Radiopharmaceuticals; Tyrosine; World Health Organization; Young Adult

The aim of this study was to compare MRI-based morphological gross tumour volumes (GTVs) to biological tumour volumes (BTVs), defined by the pathological radiotracer uptake in positron emission tomography (PET) imaging with (18)F-fluoroethyltyrosine (FET), subsequently clinical target volumes (CTVs) and finally planning target volumes (PTVs) for radiotherapy planning of glioblastoma.. Seventeen patients with glioblastoma were included into a retrospective protocol. Treatment-planning was performed using clinical target volume (CTV=BTV+20mm or CTV=GTV+20mm+inclusion of the edema) and planning target volume (PTV=CTV+5mm). Image fusion and target volume delineation were performed with OTP-Masterplan®. Initial gross tumour volume (GTV) definition was based on MRI data only or FET-PET data only (BTV), secondarily both data sets were used to define a common CTV.. FET based BTVs (median 43.9 cm(3)) were larger than corresponding GTVs (median 34.1cm(3), p=0.028), in 11 of 17 cases there were major differences between GTV/BTV. To evaluate the conformity of both planning methods, the index (CTV(MRT)∩CTV(FET))/(CTV(MRT)∪CTV(FET)) was quantified which was significantly different from 1 (0.73 ± 0.03, p<0.001).. With FET-PET-CT planning, the size and geometrical location of GTVs/BTVs differed in a majority of patients. It remains open whether FET-PET-based target definition has a relevant clinical impact for treatment planning.

Topics: Aged; Biopsy; Brain Neoplasms; Contrast Media; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal; Retrospective Studies; Statistics, Nonparametric; Tomography, X-Ray Computed; Treatment Outcome; Tyrosine

Diffuse gliomas may harbor anaplastic foci which affect prognosis and determine adjuvant therapies. Such foci are not always detected by contrast-enhancement on MRI. Recently, other modalities have been introduced, such as FET-PET for pre-diagnostic imaging and 5-aminolevulinic derived tumor fluorescence for intraoperative identification of malignant glioma tissue. The relationship between these modalities and their value for guiding biopsies during resection has not yet been elucidated in the group of diffuse gliomas.. FET-PET was performed in 30 consecutive patients with intracerebral lesions suggestive of diffuse gliomas on MRI with or without areas of contrast-enhancement. Prior to surgery patients were given 5-ALA at a dose of 20mg/kg body weight. Areas of FET uptake with a lesion/brain ratio of 1.6 or more were considered indicators of tumor. FET-PET data were corregistered with MRI data before surgery in order to obtain neuronavigated biopsies during resection, which were collected from FET positive and negative areas, analyzed for tumor fluorescence and correlated to contrast-enhancement on MRI.. 13 of 30 tumors were diagnosed as gliomas WHO Grade II, 15 as gliomas WHO Grade III and 2 as gliomas WHO Grade IV. The mean lesion/brain tissue ratio of FET uptake was significantly greater for high-grade than for low-grade gliomas (averages SD 2.323±0.754 vs. 1.453±0.538 p=0.0014). A match of FET-pos/ALA-pos biopsies was found in 70.6% (12/17) of high-grade gliomas (WHO Grade III/IV) but only in 7.7% (1/13) of low grade gliomas. Gd-neg/FET-neg/ALA-neg biopsies yielded a low-grade tumor in 46.2% (6/13). A mismatch between FET uptake and 5-ALA (FET-pos/ALA-neg) was found in 46.2% (6/13) of the low-grade and in 17.6% (3/17) of the high-grade tumors. The combination of FET-PET- and 5-ALA-positivity yielded a sensitivity for identifying high-grade glioma foci of 70.5% and a specificity of 92.3%.. In low grade gliomas 5-ALA fluorescence is the exception and FET PET is more sensitive. High grade areas in diffuse gliomas with anaplastic foci usually fluoresce, if they are FET PET positive. As a result, FET PET appears valuable for pre-operative identification of anaplastic foci and hot spots are strongly predictive for ALA-derived fluorescence, which highlight anaplastic foci during resection.

Topics: Adult; Aminolevulinic Acid; Biopsy; Brain Neoplasms; Carcinoma; Contrast Media; Female; Fluorescence; Gadolinium DTPA; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Monitoring, Intraoperative; Neurosurgical Procedures; Positron-Emission Tomography; Radiopharmaceuticals; Surgery, Computer-Assisted; Tyrosine

(1) To investigate the diagnostic value of some O-(2-[F]fluoroethyl)-L-tyrosine (F-18 FET) indices derived from the dynamic acquisition to differentiate low-grade gliomas from high-grade; (2) to analyze the course of tumor time-activity curves (TACs); and (3) to calculate the individual probability of a high-grade glioma using the logistic regression.. Seventeen low-grade (WHO I-II) and 15 high-grade (WHO III-IV) gliomas were studied with dynamic F-18 FET PET. Regions of interests were drawn over the tumor and contralateral brain, and TACs were analyzed. We considered early standardized uptake value (SUV), middle SUV, late SUV, early-to-middle SUV tumor ratio, early-to-late SUV tumor ratio; time to peak (Tpeak), in minutes, from the beginning of the dynamic acquisition up to the maximum SUV of the tumor; and SoD (sum of the frame-to-frame differences). To assess the individual probability of high-grade, logistic regression was also used.. High-grade gliomas showed significantly (P < 0.0001) higher values when compared with low-grade gliomas in early SUV, early-to-middle ratio, early-to-late ratio, Tpeak, and SoD. For the grading of gliomas, the best indices were early-to-middle ratio and Tpeak providing a diagnostic accuracy of 94%. TACs analysis provided an 87% diagnostic accuracy. For individual high-grade diagnosis, the logistic regression provided 93% sensitivity, 100% specificity, and 97% accuracy.. Early-to-middle SUV tumor ratio and Tpeak were the best indices for assessing the grading of gliomas. Since early-to-middle ratio derives from the first 35 minutes of the dynamic acquisition, the PET study could last half an hour instead of 1 hour. By logistic regression, it is possible to assess the individual probability of high-grade, useful for prognosis and treatment.

Topics: Adolescent; Adult; Aged; Brain Neoplasms; Female; Glioma; Humans; Male; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Time Factors; Tyrosine; Young Adult

The management of non-contrast-enhancing brain tumours largely depends on biopsy, which allows a differentiation of low-grade gliomas (LGG) from high-grade gliomas (HGG). The aim of this study was to compare positron emission tomography using 2-[(18)F]-fluoro-2-deoxy-D: -glucose (FDG-PET) and O-(2-[(18)F]-fluoroethyl)-L: -tyrosine (FET-PET) in terms of providing target regions for biopsies.. Fifteen consecutive patients with newly diagnosed brain tumours (n = 11) or suspected recurrence of a known LGG (n = 4), in whom MRI demonstrated no contrast enhancement, were studied by both FET-PET and FDG-PET. FET-PET, FDG-PET and MRI data were fused, and then transferred to the neurosurgical navigation system, prior to neurosurgical interventions.. Histology showed HGG (WHO grade III) in 6/15 and LGG (WHO grade II) in 9/15 patients. FET-PET revealed an increased intratumoural tracer uptake in 8/9 LGG and in 5/6 HGG. FDG-PET depicted hypermetabolic spots in 2/9 LGG and in 4/6 HGG. In 6 patients we observed an increased intratumoural uptake of both tracers. In 4 of them, the area of highest FET accumulation in the tumour corresponded to the focus of increased FDG uptake.. FET-PET appears to be superior to FDG-PET for biopsy planning in non-contrast-enhancing brain tumours. FDG-PET does not provide any additional information in this issue.

Topics: Adult; Aged; Biopsy; Brain Neoplasms; Contrast Media; Female; Fluorodeoxyglucose F18; Glioma; Humans; Male; Middle Aged; Positron-Emission Tomography; Prognosis; Recurrence; Treatment Outcome; Tyrosine

O-(2'-[(18)F]fluoroethyl)-l-tyrosine ([(18)F]FET) has gained much attention as a promising amino acid radiotracer for tumor imaging with positron emission tomography (PET) due to favorable imaging characteristics and relatively long half-life of (18)F (110min) allowing remote-site application. Here we present a novel type of chiral enantiomerically pure labeling precursor for [(18)F]FET, based on NiII complex of a Schiff's base of (S)-[N-2-(N'-benzylprolyl)amino]benzophenone (BPB) with alkylated (S)-tyrosine, Ni-(S)-BPB-(S)-Tyr-OCH2CH2X (X=OTs (3a), OMs (3b) and OTf (3c)). A series of compounds 3a-c was synthesized in three steps from commercially available reagents. Non-radioactive FET as a reference was prepared from 3a in a form of (S)-isomer and (R,S) racemic mixture. Radiosynthesis comprised two steps: (1) n.c.a. nucleophilic fluorination of 3a-c (4.5-5.0mg) in the presence of either Kryptofix 2.2.2.or tetrabutylammonium carbonate (TBAC) in MeCN at 80 degrees C for 5min, followed by (2) removal of protective groups by treating with 0.5M HCl (120 degrees C, 5min). The major advantages of this procedure are retention of enantiomeric purity during the (18)F-introduction step and easy simultaneous deprotection of amino and carboxy moieties in 3a-c. Radiochemically pure [(18)F]FET was isolated by semi-preparative HPLC (C18 mu-Bondapak, Waters) eluent aq 0.01M CH(3)COONH(4), pH 4/C(2)H(5)OH 90/10 (v/v). Overall synthesis time operated by Anatech RB 86 laboratory robot was 55min. In a series of compounds 3a-c, tosyl derivative 3a provided highest radiochemical yield (40-45%, corrected for radioactive decay). Enantiomeric purity was 94-95% and 96-97%, correspondingly, for Kryptofix and TBAC assisted fluorinations. The suggested procedure involved minimal number of synthesis steps and suits perfectly for automation in the modern synthesis modules for PET radiopharmaceuticals. Preliminary biodistribution study in experimental model of turpentine-induced aseptic abscess and Glioma35 rat's tumor (homografts) in Wistar rats has demonstrated the enhanced uptake of radiotracer in the tumor area with minimal accumulation in the inflamed tissues.

Topics: Animals; Benzophenones; Chromatography, High Pressure Liquid; Disease Models, Animal; Glioma; Molecular Conformation; Nickel; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Rats, Wistar; Schiff Bases; Skin Neoplasms; Stereoisomerism; Tyrosine