18f-fluoroethyl-l-tyrosine and Brain-Neoplasms

The diagnostic potential of PET using the amino acid analogue O-(2-[

Topics: Animals; Brain Neoplasms; Humans; Tyrosine

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

From the past decade to date, several studies related to O-(2- [18F]fluoroethyl)-L-tyrosine (18F-FET) positron emission tomography (PET) in brain tumours have been published in the literature.. The aim of this narrative review is to summarize the recent developments and the current role of 18F-FET PET in brain tumours according to recent literature data.. Main findings from selected recently published and relevant articles on the role of 18F-FET PET in neuro-oncology are described.. 18F-FET PET may be useful in the differential diagnosis between brain tumours and non-neoplastic lesions and between low-grade and high-grade gliomas. Integration of 18F-FET PET into surgical planning allows better delineation of the extent of resection beyond margins visible with standard MRI. For biopsy planning, 18F-FET PET is particularly useful in identifying malignant foci within non-contrast-enhancing gliomas. 18F-FET PET may improve the radiation therapy planning in patients with gliomas. This metabolic imaging method may be useful to evaluate treatment response in patients with gliomas and it improves the differential diagnosis between brain tumours recurrence and posttreatment changes. 18F-FET PET may provide useful prognostic information in high-grade gliomas.. Based on recent literature data 18F-FET PET may provide additional diagnostic information compared to standard MRI in neuro-oncology.

Topics: Brain Neoplasms; Humans; Positron-Emission Tomography; Tyrosine

Distinguishing radiation necrosis from brain tumor recurrence remains challenging. We performed a meta-analysis to assess the diagnostic accuracy of 2 different amino acid tracers used in positron emission tomography/computed tomography scans:. We searched for studies in 3 databases: PubMed, Embase, and Chinese Biomedical databases. The data were extracted from eligible studies and then processed with heterogeneity test, threshold effect test, and calculations of sensitivity, specificity, and area under the summary receiver operating characteristic curve. Meta-regression and subgroup analyses were performed to explore the source of heterogeneity.. A total of 48 studies (. Both

Topics: Brain Neoplasms; Diagnosis, Differential; Dihydroxyphenylalanine; Humans; Neoplasm Recurrence, Local; Positron Emission Tomography Computed Tomography; Prospective Studies; Radiation Injuries; Retrospective Studies; Tyrosine

The assessment of cerebral gliomas using magnetic resonance imaging (MRI) provides excellent structural images but cannot solve all diagnostic problems satisfactorily. The differentiation of tumour tissue from non-neoplastic changes may be difficult especially in the post-treatment phase. In recent years, positron emission tomography (PET) using radiolabelled amino acids has gained considerable interest as an additional tool to improve the diagnosis of cerebral gliomas and brain metastases. A key step for this advancement was the development of the F-18 labelled amino acid O-(2-[

Topics: Animals; Brain Neoplasms; Humans; Positron-Emission Tomography; Protein Transport; Tyrosine

The aim of this study is to present and evaluate a multiparametric and multi-modality imaging protocol applied to brain tumours and investigate correlations between these different imaging measures. In particular, we describe a method for rapid, non-invasive, quantitative imaging of water content of brain tissue, based on a single multiple-echo gradient-echo (mGRE) acquisition. We include in the processing a method for noise reduction of the multi-contrast data based on Principal Component Analysis (PCA). Noise reduction is a key ingredient to obtaining high-precision water content and transverse relaxation T

Topics: Animals; Brain Neoplasms; Diffusion; Humans; Magnetic Resonance Imaging; Molecular Imaging; Positron-Emission Tomography; Tyrosine; Water

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

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

To explore a prognostic or predictive role of MRI and O-(2-. Patients with isocitrate dehydrogenase wild-type glioblastoma ages 65 years or older were included in this. Overall survival benefit from bevacizumab plus radiotherapy compared with radiotherapy alone was observed for larger pretreatment MRI contrast-enhancing tumor [HR per cm. Large pretreatment contrast-enhancing tumor mass and higher ADCs identify patients who may experience a survival benefit from bevacizumab plus radiotherapy. Persistent

Topics: Aged; Aged, 80 and over; Bevacizumab; Brain; Brain Neoplasms; Chemoradiotherapy; Female; Glioblastoma; Humans; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Male; Positron-Emission Tomography; Progression-Free Survival; Radiopharmaceuticals; 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

In MRI of patients with recurrent glioblastoma, bevacizumab-induced normalization of tumor vascularity can be difficult to differentiate from antitumor effects. The aim of this study was to assess the utility of. MRI and FET PET were performed before and after administration of two doses of bevacizumab to 11 patients with recurrent glioblastoma. The ratio between normalized FET uptake at follow-up and baseline of the entire (volume of T2 FLAIR abnormality) and enhancing tumor were assessed for prediction of progression-free survival (PFS) and overall survival (OS). Voxel-wise Spearman correlation between normalized FET uptake and contrast-enhanced T1 signal intensity was assessed and tested as a predictor of PFS and OS.. Mean Spearman correlation between FET uptake and contrast-enhanced T1 signal intensity before therapy was 0.65 and after therapy was 0.61 (p = 0.256). The median PFS after initiation of bevacizumab therapy was 111 days, and the OS was 223 days. A post-treatment to pretreatment PET uptake ratio (mean and 90th percentile) greater than 0.7 for both entire and enhancing tumor was associated with lower PFS and OS (p < 0.001-0.049). The increase in correlation between PET uptake and contrast-enhanced T1 intensity after treatment was associated with lower PFS (p < 0.001) and OS (p = 0.049).. There is only a moderate correlation between FET PET uptake and contrast-enhanced T1 signal intensity. High posttreatment-to-pretreatment FET PET uptake ratio and increase in correlation between PET uptake and contrast-enhanced T1 signal intensity after bevacizumab treatment are associated with poor PFS and OS.

Topics: Angiogenesis Inhibitors; Bevacizumab; Brain Neoplasms; Female; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Predictive Value of Tests; 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

We investigated the value of

Topics: Adult; Aged; Aged, 80 and over; Brain Neoplasms; Combined Modality Therapy; Disease Progression; Female; Humans; Immunotherapy; Lung Neoplasms; Male; Melanoma; Middle Aged; Molecular Targeted Therapy; Retrospective Studies; Treatment Outcome; 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

Glioma stem cells (GSCs) are the source of tumor recurrence in glioblastoma and are capable of whole tumor regeneration once the treatment has concluded. Compelling evidence from the last decade suggests that GSC may arise from neural stem cells residing in the adult subventricular zone (SVZ). We report the findings of an 18F-FET PET/CT showing pathological uptake in SVZ with a tumor-background ratio of greater than 1.6, giving evidence for glioblastoma recurrence. This case highlights the particular attention to be paid to the SVZ given the possible development of GSC.

Topics: Adult; Brain Neoplasms; Female; Glioblastoma; Humans; Lateral Ventricles; Positron Emission Tomography Computed Tomography; Recurrence; Tyrosine

To evaluate whether F-fluoroethyltyrosine (FET) PET can discriminate progression from pseudoprogression of brain metastases in patients with non-small cell lung cancer undergoing immunotherapy and radiotherapy to the brain.. Retrospective analysis of F-FET PET scans in cases with documented progression of brain metastases on MRI in a cohort of 53 patients with non-small cell lung cancer receiving immune-checkpoint inhibitors and radiotherapy of brain metastases at the University Hospital of Zürich from June 2015 until January 2019. Response to radiotherapy was assessed by MRI. In case of equivocal findings and/or radiological progression in clinically asymptomatic patients, further assessment with F-FET PET was performed.. From the cohort of 53 patients, the restaging MRI showed in 30 patients (56.6%) progression of at least 1 treated metastasis. Thereof, F-FET PET was performed in 11 patients, based on the absence of neurological symptoms or presence of systemic response and physicians' decision. F-FET PET correctly identified pseudoprogression in 9 of 11 patients (81.8%). In patients who did not undergo F-FET PET, 5 of 19 (26.3%) were diagnosed with pseudoprogression.. Pseudoprogression of brain metastases occurred in 50% of patients diagnosed with progression on MRI. F-FET PET may help differentiate pseudoprogression from real progression in order to avoid discontinuation of effective therapy or unneeded interventions.

Topics: Adult; Aged; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Disease Progression; Female; Humans; Lung Neoplasms; Male; Middle Aged; Positron-Emission Tomography; Retrospective Studies; Tyrosine

The aim of this study was to derive reference values of 18F-fluoro-ethyl-L-tyrosine positron emission tomography (18F-FET-PET) uptake in normal brain and head structures to allow for differentiation from tumor tissue.. We examined the datasets of 70 patients (median age 53 years, range 15-79), whose dynamic 18F-FET-PET was acquired between January 2016 and October 2017. Maximum standardized uptake value (SUVmax), target-to-background standardized uptake value ratio (TBR), and time activity curve (TAC) of the 18F-FET-PET were assessed in tumor tissue and in eight normal anatomic structures and compared using the t-test and Mann-Whitney U-test. Correlation analyses were performed using Pearson or Spearman coefficients, and comparisons between several variables with Pearson's chi-squared tests and Kruskal-Wallis tests as well as the Benjamini-Hochberg correction.. All analyzed structures showed an 18F-FET uptake higher than background (threshold: TBR > 1.5). The venous sinuses and cranial muscles exhibited a TBR of 2.03±0.46 (confidence interval (CI) 1.92-2.14), higher than the uptake of caudate nucleus, pineal gland, putamen, and thalamus (TBR 1.42±0.17, CI 1.38-1.47). SUVmax, TBR, and TAC showed no difference in the analyzed structures between subjects with high-grade gliomas and subjects with low-grade gliomas, except the SUVmax of the pineal gland (t-tests of the pineal gland: SUVmax: p = 0.022; TBR: p = 0.411). No significant differences were found for gender and age.. Normal brain tissue demonstrates increased 18F-FET uptake compared to background tissue. Two distinct clusters have been identified, comprising venous structures and gray matter with a reference uptake of up to SUVmax of 2.99 and 2.33, respectively.

Topics: Adolescent; Adult; Aged; Biological Transport; Brain; Brain Neoplasms; Female; Humans; Male; Middle Aged; Positron-Emission Tomography; Reference Values; Tyrosine; Young Adult

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

Diagnostic accuracy in previous studies of O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) PET in patients with suspected recurrent glioma may be influenced by prolonged dynamic PET acquisitions, heterogeneous populations, different non-standard-of-care therapies, and PET scans performed at different time points post radiotherapy. We investigated the diagnostic accuracy of a 20-minute 18F-FET PET scan in MRI-suspected recurrent glioblastoma 6 months after standard radiotherapy and its ability to prognosticate overall survival (OS).. In total, 146 glioblastoma patients with 168 18F-FET PET scans were reviewed retrospectively. Patients with MRI responses to bevacizumab or undergoing re-irradiation or immunotherapy after 18F-FET PET were excluded. Maximum and mean tumor-to-background ratios (TBRmax, TBRmean) and biological tumor volume (BTV) were recorded and verified by histopathology or clinical/radiological follow-up. Thresholds of 18F-FET parameters were determined by receiver operating characteristic (ROC) analysis. Prognostic factors were investigated in Cox proportional hazards models.. Surgery was performed after 104 18F-FET PET scans, while clinical/radiological surveillance was used following 64, identifying 152 glioblastoma recurrences and 16 posttreatment changes. ROC analysis yielded thresholds of 2.0 for TBRmax, 1.8 for TBRmean, and 0.55 cm3 for BTV in differentiating recurrent glioblastoma from posttreatment changes with the best performance of TBRmax (sensitivity 99%, specificity 94%; P < 0.0001) followed by BTV (sensitivity 98%, specificity 94%; P < 0.0001). Using these thresholds, 166 18F-FET PET scans were correctly classified. Increasing BTV was associated with shorter OS (P < 0.0001).. A 20-minute 18F-FET PET scan is a powerful tool to distinguish posttreatment changes from recurrent glioblastoma 6-month postradiotherapy, and predicts OS.

Topics: Adult; Aged; Aged, 80 and over; Brain Neoplasms; Chemoradiotherapy; Combined Modality Therapy; Female; Follow-Up Studies; Glioblastoma; Humans; Immunotherapy; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Retrospective Studies; Survival Rate; Tyrosine; Young Adult

Areas of contrast enhancement (CE) on MRI are usually the target for resection or radiotherapy target volume definition in glioblastomas. However, the solid tumour mass may extend beyond areas of CE. Amino acid PET can detect parts of the tumour that show no CE. We systematically investigated tumour volumes delineated by amino acid PET and MRI in patients with newly diagnosed, untreated glioblastoma.. Preoperatively, 50 patients with neuropathologically confirmed glioblastoma underwent O-(2-[. In 43 patients (86%), the FET tumour volume was significantly larger than the CE volume (21.5 ± 14.3 mL vs. 9.4 ± 11.3 mL; P < 0.001). Forty patients (80%) showed both increased uptake of FET and CE. In these 40 patients, the spatial similarity between FET uptake and CE was low (mean DSC 0.39 ± 0.21, mean JSC 0.26 ± 0.16). Ten patients (20%) showed no CE, and one of these patients showed no FET uptake. In five patients (10%), increased FET uptake was present outside areas of FLAIR hyperintensity.. Our results show that the metabolically active tumour volume delineated by FET PET is significantly larger than tumour volume delineated by CE. Furthermore, the results strongly suggest that the information derived from both imaging modalities should be integrated into the management of patients with newly diagnosed glioblastoma.

Topics: Adult; Aged; Brain Neoplasms; Female; Glioblastoma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Tumor Burden; Tyrosine

Topics: Adult; Antineoplastic Agents; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Erlotinib Hydrochloride; Female; Humans; Lung Neoplasms; Mutation; Positron-Emission Tomography; Tyrosine

Glioblastoma (GBM) is a highly invasive brain tumor, whose cells infiltrate surrounding normal brain tissue beyond the lesion outlines visible in the current medical scans. These infiltrative cells are treated mainly by radiotherapy. Existing radiotherapy plans for brain tumors derive from population studies and scarcely account for patient-specific conditions. Here, we provide a Bayesian machine learning framework for the rational design of improved, personalized radiotherapy plans using mathematical modeling and patient multimodal medical scans. Our method, for the first time, integrates complementary information from high-resolution MRI scans and highly specific FET-PET metabolic maps to infer tumor cell density in GBM patients. The Bayesian framework quantifies imaging and modeling uncertainties and predicts patient-specific tumor cell density with credible intervals. The proposed methodology relies only on data acquired at a single time point and, thus, is applicable to standard clinical settings. An initial clinical population study shows that the radiotherapy plans generated from the inferred tumor cell infiltration maps spare more healthy tissue thereby reducing radiation toxicity while yielding comparable accuracy with standard radiotherapy protocols. Moreover, the inferred regions of high tumor cell densities coincide with the tumor radioresistant areas, providing guidance for personalized dose-escalation. The proposed integration of multimodal scans and mathematical modeling provides a robust, non-invasive tool to assist personalized radiotherapy design.

Topics: Bayes Theorem; Brain; Brain Neoplasms; Glioblastoma; Humans; Multimodal Imaging; Positron-Emission Tomography; Precision Medicine; Radiotherapy Planning, Computer-Assisted; Tyrosine

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

Glioblastoma (GB) is the most common primary malignant brain tumor. Standard medical treatment consists of a maximal safe surgical resection, subsequently radiation therapy (RT) and chemotherapy with temozolomide (TMZ). An accurate definition of the tumor volume is of utmost importance for guiding RT. In this project we investigated the feasibility and treatment response of subvolume boosting to a PET-defined tumor part.. F98 GB cells inoculated in the rat brain were imaged using T2- and contrast-enhanced T1-weighted (T1w) MRI. A dose of 20 Gy (5 × 5 mm. When comparing the dose volume histograms, a significant difference was found exclusively between the D. In this study we showed the feasibility of PET guided subvolume boosting of F98 glioblastoma in rats. No evidence was found for a beneficial effect regarding tumor response. However, improvements for dose targeting in rodents and studies investigating new targeted drugs for GB treatment are mandatory.

Topics: Animals; Brain Neoplasms; Cell Line, Tumor; Disease Models, Animal; Feasibility Studies; Female; Glioblastoma; Nitroimidazoles; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy Dosage; Radiotherapy, Image-Guided; Rats, Inbred F344; Treatment Outcome; Tumor Burden; Tyrosine

The value of early postoperative 18F-FET-PET in patients with glioblastoma (GBM) is unclear. Five-aminolevulinic acid (5-ALA) is used for fluorescence-guided resections in these patients and previous data suggest that fluorescence and 18F-FET-PET both demarcate larger tumor volumes than gadolinium enhanced magnet resonance imaging (MRI).. To correlate fluorescence with enhancing volumes on postoperative MRI and 18F-FET-PET tumor volumes, and determine the value of postoperative 18F-FET-PET for predicting survival through observational study.. GBM patients underwent fluorescence-guided resection after administration of 5-ALA followed by early postoperative MRI and 18F-FET-PET for determination of residual tissue volumes. All patients were treated with standard temozolomide radiochemotherapy and monitored for progression-free and overall survival (PFS, OS).. A total of 31 patients were included. For functional reasons, residual 5-ALA derived fluorescent tissue was left unresected in 18 patients with a median 18F-FET-PET volume of 17.82 cm3 (interquartile range 6.50-29.19). In patients without residual fluorescence, median 18F-FET-PET volume was 1.20 cm3 (interquartile range 0.87-5.50) and complete resection of gadolinium enhancing tumor was observed in 100% of patients. A 18F-FET-PET volume of above 4.3 cm3 was associated with worse OS (logrank P-value ≤ .05), also in patients with no residual contrast enhancing tumor on MRI. More patients in whom fluorescencing tissue had been removed completely had postoperative 18F-FET-PET tumor volumes below 4.3 cm3.. Postoperative 18F-FET-PET volumes predict OS and PFS. Resection of 5-ALA derived fluorescence beyond gadolinium enhancing tumor tissue leads to lower postoperative 18F-FET-PET tumor volumes and improved OS and PFS without additional deficits.

Topics: Aminolevulinic Acid; Brain Neoplasms; Gadolinium; Glioblastoma; Humans; Optical Imaging; Positron-Emission Tomography; Tyrosine

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

Stratification of glioma according to isocitrate dehydrogenase 1/2 (IDH1/2) mutation and 1p/19q codeletion status has gained major importance in the new World Health Organization (WHO) classification. Parameters derived from uptake dynamics of 18F-fluoro-ethyl-tyrosine PET (18F-FET-PET) such as minimal time-to-peak (TTPmin) allow discrimination between different prognostic glioma subgroups, too. The present study is aimed at exploring whether TTPmin analysis provides prognostic information beyond the WHO classification.. Three hundred patients with newly diagnosed WHO 2007 grades II-IV gliomas with 18F-FET-PET imaging at diagnosis were grouped into 4 subgroups (IDH1/2 mut-1p/19q codel; IDH1/2 mut-1p/19q non-codel; IDH1/2 wildtype WHO grade II and III tumors; and glioblastoma). Clinical and imaging factors such as age, Karnofsky performance score, treatment, TTPmin, and maximal tumor-to-brain ratio (TBRmax) were analyzed with regard to progression-free and overall survival (PFS and OS) via univariate and multivariate regression analysis.. PFS and OS were longest in the IDH1/2 mut-1p/19q codel subgroup, followed by IDH1/2 mut-1p/19q non-codel, IDH1/2 wildtype, and GBM (P < 0.001). Further, outcome stratified by TTPmin with a cutoff of 17.5 minutes revealed significantly longer PFS and OS in patients with TTPmin >17.5 minutes (P < 0.001 for PFS and OS). Lower TBRmax values or the absence of 18F-FET uptake was also associated with favorable outcome in the entire group. In the subgroup analyses, longer median TTPmin was associated with improved outcome specifically in the IDH1/2 mut-1p/19q non-codel group.. 18F-FET-PET-derived dynamic analysis defines prognostically distinct subgroups of IDH1/2 mutant-1p/19q non-codel gliomas which cannot be distinguished as yet by molecular marker analysis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Astrocytoma; Brain Neoplasms; Child; Chromosomes, Human, Pair 19; Female; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Mutation; Positron-Emission Tomography; Prognosis; Time Factors; Tyrosine; Young Adult

O-(2-[

Topics: Brain Neoplasms; Equipment Design; Fluorine Radioisotopes; Humans; Positron-Emission Tomography; Quality Control; Radiopharmaceuticals; Technology, Radiologic; 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

In a subset of glioblastoma (GBM) patients, the differentiation between tumor progression and tumor pseudoprogression (PsP) is challenging. This case describes a male patient suffering from isocitrate dehydrogenase 1 (IDH1) mutant GBM who demonstrated an increasing contrast-enhancing (CE) lesion on a cranial magnetic resonance imaging (cMRI) scan 8 months after radiochemotherapy. In accordance with the response assessment in neuro-oncology (RANO) criteria, the cMRI lesion was classified as recurrent tumor, although

Topics: Aged; Brain Neoplasms; Chemoradiotherapy; Disease Progression; Glioblastoma; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; 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

Topics: Animals; Brain Neoplasms; Kinetics; Male; Models, Biological; Positron-Emission Tomography; Rats; Tissue Distribution; Tyrosine

We report the case of a 40-year-old woman with a progressive right-sided hemiparesis. Standard MRI revealed a contrast-enhancing brain lesion within the left basal ganglia. Ffluoroethyl-L-tyrosine (F-FET) PET showed a distinct tracer uptake (lesion-to-brain ratio [LBR]: LBRmax = 2.03, LBRmean = 1.68) with a significant larger metabolic lesion volume than contrast-enhancement in MRI, indicating cerebral glioma. Surprisingly, histopathologic analysis demonstrated central nervous system toxoplasmosis with pronounced inflammatory reaction (reactive astrogliosis, microglia activation, macrophage, and T-lymphocyte infiltration), which was associated with strong LAT1/LAT2/CD98 expression. In conclusion, inflammatory brain lesions, such as cerebral toxoplasmosis, represent a potential pitfall of F-FET PET mimicking a brain tumor.

Topics: Acquired Immunodeficiency Syndrome; Adaptor Proteins, Signal Transducing; Adult; Biological Transport; Brain Neoplasms; Diagnosis, Differential; Female; Gene Expression Regulation; Humans; Inflammation; Large Neutral Amino Acid-Transporter 1; Positron-Emission Tomography; Toxoplasmosis, Cerebral; Tyrosine

O-(2-

Topics: Adult; Aged; Amino Acid Transport Systems; Amino Acids; Biological Transport, Active; Brain Neoplasms; Diagnosis, Differential; Diagnostic Errors; Epilepsy; Female; Humans; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tyrosine

Abnormal tryptophan metabolism via the kynurenine pathway is involved in the pathophysiology of a variety of human diseases including cancers. α-. Xenograft mouse models of glioblastoma and metastatic brain tumors (from lung and breast cancer) were developed by subcutaneous implantation of patient tumor fragments. Dynamic PET scans with

Topics: Animals; Biomarkers, Tumor; Brain Neoplasms; Carbon Radioisotopes; Cell Line, Tumor; Female; Humans; Metabolic Clearance Rate; Mice; Mice, Inbred BALB C; Mice, SCID; Molecular Imaging; Organ Specificity; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tissue Distribution; Tryptophan; Tyrosine

We investigated the potential of textural feature analysis of O-(2-[. Forty-seven patients with contrast-enhancing brain lesions (n = 54) on MRI after radiotherapy of brain metastases underwent dynamic. Diagnostic accuracy increased from 81 % for TBR. Textural feature analysis in combination with TBRs may have the potential to increase diagnostic accuracy for discrimination between brain metastasis recurrence and radiation injury, without the need for dynamic. • Textural feature analysis provides quantitative information about tumour heterogeneity • Textural features help improve discrimination between brain metastasis recurrence and radiation injury • Textural features might be helpful to further understand tumour heterogeneity • Analysis does not require a more time consuming dynamic PET acquisition.

Topics: Adolescent; Aged; Brain; Brain Neoplasms; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Positron Emission Tomography Computed Tomography; Radiation Injuries; Radiometry; Tyrosine; Young Adult

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

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

(S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid (18F-FSPG) is a novel radiopharmaceutical for Positron Emission Tomography (PET) imaging. It is a glutamate analogue that can be used to measure xC- transporter activity. This study was performed to assess the feasibility of 18F-FSPG for imaging orthotopic brain tumors in small animals and the translation of this approach in human subjects with intracranial malignancies.. For the small animal study, GS9L glioblastoma cells were implanted into brains of Fischer rats and studied with 18F-FSPG, the 18F-labeled glucose derivative 18F-FDG and with the 18F-labeled amino acid derivative 18F-FET. For the human study, five subjects with either primary or metastatic brain cancer were recruited (mean age 50.4 years). After injection of 300 MBq of 18F-FSPG, 3 whole-body PET/Computed Tomography (CT) scans were obtained and safety parameters were measured. The three subjects with brain metastases also had an 18F-FDG PET/CT scan. Quantitative and qualitative comparison of the scans was performed to assess kinetics, biodistribution, and relative efficacy of the tracers.. In the small animals, the orthotopic brain tumors were visualized well with 18F-FSPG. The high tumor uptake of 18F-FSPG in the GS9L model and the absence of background signal led to good tumor visualization with high contrast (tumor/brain ratio: 32.7). 18F-FDG and 18F-FET showed T/B ratios of 1.7 and 2.8, respectively. In the human pilot study, 18F-FSPG was well tolerated and there was similar distribution in all patients. All malignant lesions were positive with 18F-FSPG except for one low-grade primary brain tumor. In the 18F-FSPG-PET-positive tumors a similar T/B ratio was observed as in the animal model.. 18F-FSPG is a novel PET radiopharmaceutical that demonstrates good uptake in both small animal and human studies of intracranial malignancies. Future studies on larger numbers of subjects and a wider array of brain tumors are planned.. ClinicalTrials.gov NCT01186601.

Topics: Adult; Aged; Animals; Brain Neoplasms; Case-Control Studies; Cell Line, Tumor; Disease Models, Animal; Female; Fluorodeoxyglucose F18; Glioblastoma; Glutamic Acid; Heterografts; Humans; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Tomography, X-Ray Computed; Tyrosine

Complete resection of contrast-enhancing tumor is an important prognostic factor in glioblastoma therapy. The current clinical standard for control of resection is magnetic resonance imaging (MRI). (18)F-Fluoroethyl-l-thyrosine (FET) is a positron emission tomography (PET) radiopharmaceutical applicable for widespread use because of its long half-life radionuclide. We assessed the sensitivity of postoperative MRI versus FET-PET to detect residual tumor and the impact of the time interval between resection and FET-PET.. MRI and FET-PET were performed preoperatively and postoperatively in 62 patients undergoing 63 operations. FET-PET was performed in 43 cases within 72 hours after resection and in 20 cases >72 hours after resection. Detection and measurement of volume of residual tumors were compared. Correlations between residual tumor detection and timing of PET after resection and recurrence were examined.. Complete resection was confirmed by both imaging modalities in 44% of cases, and residual tumor was detected consistently in 37% of cases. FET-PET detected residual tumor in 14% of cases in which MRI showed no residual tumor. MRI showed residual tumors in 5% of cases that were not identified by PET. Average PET-based residual tumor volume was higher than MRI-based volume (3.99 cm(3) vs. 1.59 cm(3)). Detection of and difference in volume of residual tumor were not correlated with timing of PET after resection or recurrence status.. Postoperative FET-PET revealed residual tumor with higher sensitivity than MRI and showed larger tumor volumes. In this series, performing PET >72 hours after resection did not influence the results of PET. We recommend FET-PET as a helpful adjunct in addition to MRI for postoperative assessment of residual tumor.

Topics: Adult; Aged; Aged, 80 and over; Brain; Brain Neoplasms; Female; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm, Residual; Positron-Emission Tomography; Postoperative Period; Preoperative Period; Radiopharmaceuticals; Sensitivity and Specificity; Time Factors; Tyrosine

The radiolabeled amino acid O-(2-(18)F-fluoroethyl)-L-tyrosine (FET) and thymidine analogue 3'-deoxy-3'-(18)F-fluorothymidine (FLT) are widely used for positron emission tomography (PET) brain tumor imaging; however, comparative studies are scarce. The aim of this study therefore was to compare FLT and FET PET for the assessment of anti-VEGF response in glioblastoma xenografts.. Xenografts with confirmed intracranial glioblastoma were treated with anti-VEGF therapy (B20-4.1) or saline as control. Weekly bioluminescence imaging (BLI), FLT and FET PET/CT were used to follow treatment response. Tracer uptake of FLT and FET was quantified using maximum standardized uptake (SUVmax) values and tumor-to-background ratios (TBRs). Survival, the Ki67 proliferation index and micro-vessel density (MVD) were evaluated.. In contrast to FLT TBRs, FET TBRs were significantly lower as early as one week after treatment initiation in the anti-VEGF group as compared to the control group. Following two weeks of treatment, both FLT and FET TBRs were significantly lower in the anti-VEGF group. In contrast, no significant difference between the treatment groups was detected using BLI. Furthermore, we found a significantly lower MVD in the anti-VEGF group as compared to the control group. However, we found no difference in the Ki67 proliferation index or mean survival time.. FET appears to be a more sensitive tracer than FLT to measure early response to anti-VEGF therapy with PET. Advances in knowledge and implications for patient care FET PET appears to be an early predictor of anti-VEGF efficacy. Confirmation of these results in clinical studies is needed.

Topics: Animals; Bevacizumab; Brain Neoplasms; Cell Transformation, Neoplastic; Dideoxynucleosides; Female; Glioblastoma; HEK293 Cells; Humans; Mice; Microvessels; Positron-Emission Tomography; Survival Analysis; Tyrosine; Vascular Endothelial Growth Factor A

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

Discrimination between (high-grade) brain tumor recurrence and radiation necrosis (RN) remains a diagnostic challenge because both entities have similar imaging characteristics on conventional magnetic resonance imaging (MRI). Metabolic imaging, such as positron emission tomography (PET) could overcome this diagnostic dilemma. In this study, we investigated the potential of 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG), O-(2-[(18)F]-fluoroethyl)-L-tyrosine ((18)F-FET), and [(18)F]-Fluoromethyl-dimethyl-2-hydroxyethylammonium ((18)F-fluoromethylcholine, (18)F-FCho) PET in discriminating high-grade tumor from RN.. We developed a glioblastoma (GB) rat model by inoculating F98 GB cells into the right frontal region. Induction of RN was achieved by irradiating the right frontal region with 60 Gy using three arcs with a beam aperture of 3×3 mm (n=3). Dynamic PET imaging with (18)F-FDG, (18)F-FET, and (18)F-FCho, as well as (18)F-FDG PET at a delayed time interval (240 min postinjection), was acquired.. MRI revealed contrast-enhancing tumors at 15 days after inoculation (n=4) and contrast-enhancing RN lesions 5-6 months postirradiation (n=3). On (18)F-FDG PET, the mean lesion-to-normal ratio (LNRmean) was significantly higher in GB than in RN (p=0.034). The difference in the LNRmean between tumors and RN was higher on the late (18)F-FDG PET images than on the PET images reconstructed from the last time frame of the dynamic acquisition (this is at a conventional time interval). LNRs obtained from (18)F-FCho PET were not significantly different between GB and RN (p=1.000). On (18)F-FET PET, the LNRmean was significantly higher in GB compared to RN (p=0.034).. Unlike (18)F-FCho, (18)F-FDG and (18)F-FET PET were effective in discriminating GB from RN. Interestingly, in the case of (18)F-FDG, delayed PET seems particularly useful.. Our results suggest that (delayed) (18)F-FDG and (18)F-FET PET can be used to discriminate GB (recurrence) from RN. Confirmation of these results in clinical studies is needed.

Topics: Animals; Brain Neoplasms; Cell Line, Tumor; Choline; Diagnosis, Differential; Female; Fluorodeoxyglucose F18; Glioblastoma; Necrosis; Neoplasm Grading; Positron-Emission Tomography; Radiation Injuries; Radioactive Tracers; Radiopharmaceuticals; Rats; Recurrence; Tyrosine

The aim of this prospective longitudinal study was to identify static and dynamic O-(2-[(18)F]fluoroethyl)-L-tyrosine PET ((18)FET-PET)-derived imaging biomarkers in patients with glioblastoma (GBM).. Seventy-nine patients with newly diagnosed GBM were included; 42 patients underwent stereotactic biopsy (unresectable tumors) and 37 patients microsurgical tumor resection. All patients were scheduled to receive radiotherapy plus concomitant and adjuvant temozolomide (RCx/TMZ). (18)FET-PET evaluation using static and dynamic analysis was done before biopsy/resection, after resection, 4 to 6 weeks following RCx, and after 3 cycles of TMZ. Endpoints were survival and progression-free-survival. Prognostic factors were obtained from proportional hazards models.. Biological tumor volume before RCx (BTV(preRCx)) was the most important (18)FET-PET-derived imaging biomarker and was independent of MGMT promoter methylation and clinical prognostic factors: patients with smaller BTV(preRCx) had significantly longer progression-free and overall survival (OS). (18)FET time-activity curves (TACs) before treatment and their changes after RCx were also related to outcome; patients with initially increasing TACs experienced longer OS.. BTV(preRCx) and TAC represent important (18)FET-PET-derived imaging biomarkers in GBM. Increasing TACs are associated with prolonged OS. The BTV(preRCx) is a strong prognostic factor for progression-free survival and OS independent of the mode of surgery. Our data furthermore suggest that patients harboring resectable GBM might benefit from maximal PET-guided tumor resection.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Brain; Brain Neoplasms; Chemoradiotherapy; Combined Modality Therapy; Dacarbazine; Disease-Free Survival; Female; Glioblastoma; Humans; Longitudinal Studies; Male; Microsurgery; Middle Aged; Neurosurgical Procedures; Positron-Emission Tomography; Prospective Studies; Temozolomide; Treatment Outcome; Tumor Burden; Tyrosine

Conflicting data exist for anti-cancer effects of anti-placental growth factor (anti-PlGF) in combination with anti-VEGF. Still, this treatment combination has not been evaluated in intracranial glioblastoma (GBM) xenografts. In clinical studies, position emission tomography (PET) using the radiolabeled amino acid O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) and magnetic resonance imaging (MRI) add complementary but distinct information about glioma growth; however, the value of 18F-FET MicroPET combined with MicroMRI has not been investigated preclinically. Here we examined the use of 18F-FET MicroPET and MicroMRI for evaluation of anti-VEGF and anti-PlGF treatment response in GBM xenografts.. Mice with intracranial GBM were treated with anti-VEGF, anti-PlGF + anti-VEGF or saline. Bioluminescence imaging (BLI), 18F-FET MicroPET and T2-weighted (T2w)-MRI were used to follow tumour development. Primary end-point was survival, and tumours were subsequently analysed for Ki67 proliferation index and micro-vessel density (MVD). Further, PlGF and VEGFR-1 expression were examined in a subset of the xenograft tumours and in 13 GBM patient tumours.. Anti-VEGF monotherapy increased survival and decreased 18F-FET uptake, BLI and MVD, while no additive effect of anti-PlGF was observed. 18F-FET SUV max tumour-to-brain (T/B) ratio was significantly lower after one week (114 ± 6%, n = 11 vs. 143 ± 8%, n = 13; p = 0.02) and two weeks of treatment (116 ± 12%, n = 8 vs. 190 ± 24%, n = 5; p = 0.02) in the anti-VEGF group as compared with the control group. In contrast, T2w-MRI volume was unaffected by anti-VEGF. Gene expression of PlGF and VEGFR-1 in xenografts was significantly lower than in patient tumours.. 18F-FET PET was feasible for anti-angiogenic response evaluation and superior to T2w-MRI; however, no additive anti-cancer effect of anti-PlGF and anti-VEGF was observed. Thus, this study supports use of 18F-FET PET for response evaluation in future studies.

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cell Line, Tumor; Cell Transformation, Neoplastic; Drug Synergism; Female; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Magnetic Resonance Imaging; Membrane Proteins; Mice; Microvessels; Multimodal Imaging; Optical Imaging; Positron-Emission Tomography; RNA, Messenger; Survival Analysis; Tomography, X-Ray Computed; Treatment Outcome; Tyrosine; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1

Here we compare translocator protein (TSPO) imaging using 6-chloro-2-(4'-(123)I-iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide SPECT ((123)I-CLINDE) and amino acid transport imaging using O-(2-(18)F-fluoroethyl)-l-tyrosine PET ((18)F-FET) and investigate whether (123)I-CLINDE is superior to (18)F-FET in predicting progression of glioblastoma multiforme (GBM) at follow-up.. Three patients with World Health Organization grade IV GBM were scanned with (123)I-CLINDE SPECT, (18)F-FET PET, and gadolinium-enhanced MR imaging. Molecular imaging data were compared with follow-up gadolinium-enhanced MR images or contrast-enhanced CT scans.. The percentage overlap between volumes of interest (VOIs) of increased (18)F-FET uptake and (123)I-CLINDE binding was variable (12%-42%). The percentage overlap of MR imaging baseline VOIs was greater for (18)F-FET (79%-93%) than (123)I-CLINDE (15%-30%). In contrast, VOIs of increased contrast enhancement at follow-up compared with baseline overlapped to a greater extent with baseline (123)I-CLINDE VOIs than (18)F-FET VOIs (21% vs. 8% and 72% vs. 55%).. Our preliminary results suggest that TSPO brain imaging in GBM may be a useful tool for predicting tumor progression at follow-up and may be less susceptible to changes in blood-brain barrier permeability than (18)F-FET. Larger studies are warranted to test the clinical potential of TSPO imaging in GBM, including presurgical planning and radiotherapy.

Topics: Aged; Biomarkers, Tumor; Brain Neoplasms; Bridged Bicyclo Compounds, Heterocyclic; Female; Fluorodeoxyglucose F18; Gadolinium; Glioblastoma; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Molecular Imaging; Radiopharmaceuticals; Receptors, GABA; Reproducibility of Results; Sensitivity and Specificity; Tissue Distribution; Tomography, Emission-Computed; Tyrosine

The knowledge of exact tumor margins is of importance for the treating neurosurgeon, radiotherapist, and oncologist alike. The aim of this study was to investigate whether tumor volume and tumor margins acquired by magnetic resonance imaging (MRI) are congruent with the findings acquired by O-(2-(18F)-fluoroethyl)-L-tyrosine-positron emission tomography (FET-PET).. Patients received FET-PET and MRI before surgery for brain metastases. Metastases were quantified by calculating tumor-to-background uptake ratios using FET uptake. PET and MRI-based tumor volumes, as well as areas of intersection, were assessed.. Forty-one patients were enrolled in the study. The maximum tumor-to-background uptake ratio measured in all of our patients harboring histologically proven viable tumor tissue was >1.6. Absolute tumor volumes acquired by FET-PET and MRI were not congruent in our patient cohort, and tumors identified in FET-PET and MRI only partially overlapped. The ratio of intersection (intersection of tumor defined by MRI and tumor defined by FET-PET at the ratio of tumor defined by FET-PET) was within a range of 0.27-0.68 when applying the different thresholds.. Our study therefore indicates that treatment planning based on MRI or PET only might have a substantial risk of undertreatment at the tumor margins. These findings could have important implications for the planning of surgery as well as radiotherapy, although they have to be validated in further studies.

Topics: Adult; Aged; Brain Neoplasms; Female; Fluorodeoxyglucose F18; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; Prognosis; Radiopharmaceuticals; Tumor Burden; Tyrosine

O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET, [(18)F]1) is a useful amino-acid-based imaging agent for brain tumors. This paper reports the synthesis and evaluation of three FET prodrugs, O-(2-[(18)F]fluoroethyl)-L-tyrosyl-L-glycine (FET-Gly, [(18)F]2), O-(2-[(18)F]fluoroethyl)-L-tyrosyl-L-alanine (FET-Ala, [(18)F]3) and N-acetyl O-(2-[(18)F]fluoroethyl)-L-tyrosine (AcFET, [(18)F]4), which could be readily hydrolyzed to FET in vivo for tumor imaging. We investigated their metabolism in the blood and imaging properties in comparison to FET ([(18)F]1).. Three new [(18)F]FET derivatives, 2-4, were prepared from their corresponding tosylate-precursors through nucleophilic fluorination and subsequent deprotection reactions. In vitro uptake studies were carried out in 9L glioma cancer cell lines. In vitro and in vivo hydrolysis studies were conducted to evaluate the hydrolysis of FET prodrugs in blood and in Fisher 344 rats. Biodistribution and PET imaging studies were then performed in rats bearing 9L tumors.. New FET prodrugs were prepared with 3-28% decay corrected radiochemical yields, good enantiomeric purity (>95%) and high radiochemical purity (>95%). FET-Gly ([(18)F]2), FET-Ala ([(18)F]3), and AcFET ([(18)F]4) exhibited negligible uptake in comparison to the high uptake of FET ([(18)F]1) in 9L cells. Metabolism studies of FET-Gly ([(18)F]2), FET-Ala ([(18)F]3), and AcFET ([(18)F]4) in rat and human blood showed that FET-Ala ([(18)F]3) was hydrolyzed to FET ([(18)F]1) faster than FET-Gly ([(18)F]2) or AcFET ([(18)F]4). Most of the FET-Ala (79%) was converted to FET ([(18)F]1) within 5min in blood in vivo. Biodistribution studies demonstrated that FET-Ala ([(18)F]3) displayed the highest tumor uptake. The tumor-to-background ratios of FET-Ala ([(18)F]3) and FET ([(18)F]1) were comparable and appeared to be better than those of FET-Gly ([(18)F]2) and AcFET ([(18)F]4). PET imaging studies showed that both FET ([(18)F]1) and FET-Ala ([(18)F]3) could visualize tumors effectively, and that they share similar imaging characteristics.. FET-Ala ([(18)F]3) demonstrated promising properties as a prodrug of FET ([(18)F]1), which could be used in PET imaging of tumor amino acid metabolism.

Topics: Amidohydrolases; Animals; Biological Transport; Brain Neoplasms; Cell Line, Tumor; Chemistry Techniques, Synthetic; Dipeptidases; Humans; Hydrolysis; Positron-Emission Tomography; Prodrugs; Rats; Tyrosine

Both (18)F-fluorodihydroxyphenylalanine ((18)F-DOPA) and (18)F-fluoroethyltyrosine ((18)F-FET) have already been used successfully for imaging of brain tumors. The aim of this study was to evaluate differences between these 2 promising tracers to determine the consequences for imaging protocols and the interpretation of findings.. Forty minutes of dynamic PET imaging were performed on 2 consecutive days with both (18)F-DOPA and (18)F-FET in patients with recurrent low-grade astrocytoma (n = 8) or high-grade glioblastoma (n = 8). Time-activity-curves (TACs), standardized uptake values (SUVs) and compartment modeling of both tracers were analyzed, respectively.. The TAC of DOPA-PET peaked at 8 minutes p.i. with SUV 5.23 in high-grade gliomas and 10 minutes p.i. with SUV 4.92 in low-grade gliomas. FET-PET peaked at 9 minutes p.i. with SUV 3.17 in high-grade gliomas and 40 minutes p.i. with SUV 3.24 in low-grade gliomas. Neglecting the specific uptake of DOPA into the striatum, the tumor-to-brain and tumor-to-blood ratios were higher for DOPA-PET. Kinetic modeling demonstrated a high flow constant k1 (mL/ccm/min), representing cellular internalization through AS-transporters, for DOPA in both high-grade (k1 = 0.59) and low-grade (k1 = 0.55) tumors, while lower absolute values and a relevant dependency from tumor-grading (high-grade k1 = 0.43; low-grade k1 = 0.33) were observed with FET.. DOPA-PET demonstrates superior contrast ratios for lesions outside the striatum, but SUVs do not correlate with grading. FET-PET can provide additional information on tumor grading and benefits from lower striatal uptake but presents lower contrast ratios and requires prolonged imaging if histology is not available in advance due to a more variable time-to-peak.

Topics: Astrocytoma; Brain Neoplasms; Dihydroxyphenylalanine; Glioblastoma; Humans; Neoplasm Recurrence, Local; Positron-Emission Tomography; Tyrosine

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

Brain tumor imaging is challenging. Although 18F-FET PET is widely used in the clinic, the value of 18F-FET MicroPET to evaluate brain tumors in xenograft has not been assessed to date. The aim of this study therefore was to evaluate the performance of in vivo 18F-FET MicroPET in detecting a treatment response in xenografts. In addition, the correlations between the 18F-FET tumor accumulation and the gene expression of Ki67 and the amino acid transporters LAT1 and LAT2 were investigated. Furthermore, Ki67, LAT1 and LAT2 gene expression in xenograft and archival patient tumors was compared.. Human GBM cells were injected orthotopically in nude mice and 18F-FET uptake was followed by weekly MicroPET/CT. When tumor take was observed, mice were treated with CPT-11 or saline weekly. After two weeks of treatment the brain tumors were isolated and quantitative polymerase chain reaction were performed on the xenograft tumors and in parallel on archival patient tumor specimens.. The relative tumor-to-brain (T/B) ratio of SUV max was significantly lower after one week (123 ± 6%, n = 7 vs. 147 ± 6%, n = 7; p = 0.018) and after two weeks (142 ± 8%, n = 5 vs. 204 ± 27%, n = 4; p = 0.047) in the CPT-11 group compared with the control group. Strong negative correlations between SUV max T/B ratio and LAT1 (r = -0.62, p = 0.04) and LAT2 (r = -0.67, p = 0.02) were observed. In addition, a strong positive correlation between LAT1 and Ki67 was detected in xenografts. Furthermore, a 1.6 fold higher expression of LAT1 and a 23 fold higher expression of LAT2 were observed in patient specimens compared to xenografts.. 18F-FET MicroPET can be used to detect a treatment response to CPT-11 in GBM xenografts. The strong negative correlation between SUV max T/B ratio and LAT1/LAT2 indicates an export transport function. We suggest that 18F-FET PET may be used for detection of early treatment response in patients.

Topics: Animals; Antineoplastic Agents, Phytogenic; Brain; Brain Neoplasms; Camptothecin; Cell Line, Tumor; Female; Glioblastoma; Heterografts; Humans; Irinotecan; Mice, Nude; Neuroimaging; Positron-Emission Tomography; 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

Treatment of recurrent glioblastoma (rGBM) remains an unsolved clinical problem. Reirradiation (re-RT) can be used to treat some patients with rGBM, but as a monotherapy it has only limited efficacy. Chloroquine (CQ) is an anti-malaria and immunomodulatory drug that may inhibit autophagy and increase the radiosensitivity of GBM.. Between January 2012 and August 2013, we treated five patients with histologically confirmed rGBM with re-RT and 250 mg CQ daily.. Treatment was very well tolerated; no CQ-related toxicity was observed. At the first follow-up 2 months after finishing re-RT, two patients achieved partial response (PR), one patient stable disease (SD), and one patient progressive disease (PD). One patient with reirradiated surgical cavity did not show any sign of PD.. In this case series, we observed encouraging responses to CQ and re-RT. We plan to conduct a CQ dose escalation study combined with re-RT.

Topics: Adult; Brain Neoplasms; Chloroquine; Feasibility Studies; Female; Glioblastoma; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Pilot Projects; Positron-Emission Tomography; Radiation-Sensitizing Agents; Radiopharmaceuticals; Radiotherapy Dosage; Radiotherapy, Image-Guided; Treatment Outcome; 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

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

Topics: Adult; Aged; Brain Neoplasms; Chemoradiotherapy; Contrast Media; Disease Progression; Disease-Free Survival; Female; Gadolinium; Glioblastoma; Humans; Kaplan-Meier Estimate; Magnetic Resonance Imaging; Male; Middle Aged; Neurosurgical Procedures; Positron-Emission Tomography; Prognosis; Proportional Hazards Models; Prospective Studies; Radiopharmaceuticals; Survival Analysis; Treatment Outcome; Tyrosine

The aim of the present study was to evaluate factors predicting the recurrence pattern determined by [(18)F]FET-PET imaging in patients with newly diagnosed glioblastoma after combined radio-chemotherapy treated according to the EORTC/NCIC trial.. Seventy-nine patients with newly diagnosed GBM treated with radiotherapy plus temozolomide (75 mg/m(2)/d) followed by adjuvant cyclic (5/28 days) temozolomide (150-200 mg/m(2)) were retrospectively analysed. Recurrence patterns were assessed by means of positron-emission-tomography with [(18)F]FET and additional MRI; in 54 patients MGMT methylation status was evaluated.. Whilst 49.4% of the patients had an in-field recurrence, 12.6% an ex-field recurrence and 3.8% a recurrence at the field margin, 34.2% of the patients did not relapse during follow-up (median 595 days). Considering all patients included in this study, 41.5% (12/29) of the MGMT methylated population had no relapse, 37.9% (11/29) had an in-field-recurrence and 20.7% (6/29) an ex-field/marginal recurrence, whilst 28.0% (7/25) of the MGMT unmethylated population had no relapse, 64.0% (16/25) had an in-field-recurrence and 8.0% (2/25) an ex-field/marginal recurrence (p=0.15).. After the administration of temozolomide concomitant with and adjuvant to radiotherapy in patients with glioblastoma, the pattern determined by [(18)F]FET-PET seems to be associated with MGMT methylation status.

Topics: Adult; Aged; Aged, 80 and over; Brain Neoplasms; Chemoradiotherapy; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Female; Glioblastoma; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Tumor Suppressor Proteins; Tyrosine

Early detection of treatment response in glioma patients after radiochemotherapy (RCX) is uncertain because treatment-related contrast enhancement in magnetic resonance imaging can mimic tumor progression. Positron emission tomography (PET) using the amino acid tracer [(18)F]fluoroethyltyrosine (FET) seems to be a promising tool for treatment monitoring. The aim of this prospective study was to evaluate the prognostic value of early changes of FET uptake after postoperative RCX in glioblastomas.. Twenty-two patients with glioblastoma were treated by surgery and subsequent RCX (whole dose 60-72 Gy). The FET-PET studies were performed before RCX, 7-10 days and 6-8 weeks after completion of RCX. Early treatment response in PET was defined as a decrease of the maximal tumor-to-brain ratio (TBR(max)) of FET uptake after RCX of more than 10%. The prognostic value of early changes of FET uptake after RCX was evaluated using Kaplan-Maier estimates for median disease-free survival and overall survival.. The median overall and disease-free survival of the patients was 14.8 and 7.8 months. There were 16 early responders in FET-PET (72.7%) and 6 nonresponders (27.3%). Early PET responders had a significantly longer median disease-free survival (10.3 vs. 5.8 months; p < 0.01) and overall survival ("not reached" vs. 9.3 months; p < 0.001). No statistically significant differences between the patient subgroups were found concerning the defined prognostic parameters.. FET-PET is a sensitive tool to predict treatment response in patients with glioblastomas at an early stage after RCX.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Brain Neoplasms; Combined Modality Therapy; Dacarbazine; Disease-Free Survival; Female; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Prognosis; Prospective Studies; Radiopharmaceuticals; Temozolomide; 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