o-(2-fluoroethyl)tyrosine and Glioma

Positron emission tomography (PET) imaging using amino acid tracers has in recent years become widely used in the diagnosis and prediction of disease course in diffuse low-grade gliomas (LGG). However, implications of preoperative PET for treatment and prognosis in this patient group have not been systematically studied. The aim of this systematic review was to evaluate the preoperative diagnostic and prognostic value of amino acid PET in suspected diffuse LGG. Medline, Cochrane Library, and Embase databases were systematically searched using keywords "PET," "low-grade glioma," and "amino acids tracers" with their respective synonyms. Out of 2137 eligible studies, 28 met the inclusion criteria. Increased amino acid uptake (lesion/brain) was consistently reported among included studies; in 25-92% of subsequently histopathology-verified LGG, in 83-100% of histopathology-verified HGG, and also in some non-neoplastic lesions. No consistent results were found in studies reporting hot spot areas on PET in MRI-suspected LGG. Thus, the diagnostic value of amino acid PET imaging in suspected LGG has proven difficult to interpret, showing clear overlap and inconsistencies among reported results. Similarly, the results regarding the prognostic value of PET in suspected LGG and the correlation between uptake ratios and the molecular tumor status of LGG were conflicting. This systematic review illustrates the difficulties with prognostic studies presenting data on group-level without adjustment for established clinical prognostic factors, leading to a loss of additional prognostic information. We conclude that the prognostic value of PET is limited to analysis of histological subgroups of LGG and is probably strongest when using kinetic analysis of dynamic FET uptake parameters.

Topics: Brain Neoplasms; Carbon Radioisotopes; Glioma; Humans; Methionine; Positron-Emission Tomography; Preoperative Period; Radiopharmaceuticals; Tyrosine

The purpose of this prospective study was to clarify the value of FLT PET and FET PET for the noninvasive grading and prognosis of newly diagnosed gliomas.. Twenty patients with newly diagnosed gliomas were investigated with FLT and FET PET before surgery. FLT and FET uptakes were assessed by the maximum standardized uptake (SUVmax) of tumor, and the ratio to uptake in the normal brain parenchyma (TNR). All tumors were graded by WHO system.. FLT PET detected all 17 high-grade gliomas (HGG) and did not detect all 3 low-grade gliomas (LGG). FET PET detected all 20 HGG and LGG regardless of grading. The average FLT SUVmax in HGG and LGG was 1.51 ± 0.72 and 0.30 ± 0.07, and the average FLT TNR in HGG and LGG was 5.52 ± 3.09 and 1.12 ± 0.14, respectively. The differences of FLT SUVmax and TNR between HGG and LGG were statistically significant (p=0.0069, p=0.0070). The average FET SUVmax in HGG and LGG was 2.68 ± 0.86 and 1.36 ± 0.15, and the average FET TNR in HGG and LGG was 2.31 ± 0.73 and 1.27 ± 0.12, respectively. The differences of FET SUVmax and TNR between HGG and LGG were statistically significant (p=0.0129, p=0.0095).. FET PET has higher sensitivity in detection of gliomas rather than FLT PET, but it seems that FLT PET is better than FET PET for noninvasive grading and predicting prognosis of newly diagnosed gliomas, considering high contrast of FLT and overlap of FET uptakes between HGG and LGG.

Topics: Adult; Aged; Brain Neoplasms; Dideoxynucleosides; Female; Glioma; Humans; Male; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Prognosis; Prospective Studies; Tyrosine

The purpose of the study is to assess the contribution of (18)F-fluoro-ethyl-tyrosine ((18)F-FET) positron emission tomography (PET) in the delineation of gross tumor volume (GTV) in patients with high-grade gliomas compared with magnetic resonance imaging (MRI) alone.. The study population consisted of 18 patients with high-grade gliomas. Seven image segmentation techniques were used to delineate (18)F-FET PET GTVs, and the results were compared to the manual MRI-derived GTV (GTV(MRI)). PET image segmentation techniques included manual delineation of contours (GTV(man)), a 2.5 standardized uptake value (SUV) cutoff (GTV(2.5)), a fixed threshold of 40% and 50% of the maximum signal intensity (GTV(40%) and GTV(50%)), signal-to-background ratio (SBR)-based adaptive thresholding (GTV(SBR)), gradient find (GTV(GF)), and region growing (GTV(RG)). Overlap analysis was also conducted to assess geographic mismatch between the GTVs delineated using the different techniques.. Contours defined using GTV(2.5) failed to provide successful delineation technically in three patients (18% of cases) as SUV(max) < 2.5 and clinically in 14 patients (78% of cases). Overall, the majority of GTVs defined on PET-based techniques were usually smaller than GTV(MRI) (67% of cases). Yet, PET detected frequently tumors that are not visible on MRI and added substantially tumor extension outside the GTV(MRI) in six patients (33% of cases).. The selection of the most appropriate (18)F-FET PET-based segmentation algorithm is crucial, since it impacts both the volume and shape of the resulting GTV. The 2.5 SUV isocontour and GF segmentation techniques performed poorly and should not be used for GTV delineation. With adequate setting, the SBR-based PET technique may add considerably to conventional MRI-guided GTV delineation.

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

Amino acid transport and protein synthesis are important steps of tumor growth. We investigated the time course of tumor metabolism in low-grade gliomas (LGG) during temozolomide chemotherapy, and compared metabolic responses as measured with positron emission tomography (PET) with volume responses as revealed by magnetic resonance imaging (MR). A homogeneous population of 11 patients with progressive non-enhancing LGG was prospectively studied. Imaging was done at 6-months intervals starting six months, and in a second series starting three months after treatment initiation. F-18 fluoro-ethyl-L-tyrosine (FET) uptake was quantified with PET as metabolically active tumor volume, and was compared with the tumor volume on MR. Response was defined as >or=10% reduction of the initial tumor volume. Eight patients showed metabolic responses. Already 3 months after start of chemotherapy the active FET volumes decreased in 2 patients to a mean of 44% from baseline. First MR volume responses were noted at 6 months. Responders showed a volume reduction to 31 +/- 23% (mean +/- SD) from baseline for FET, and to 73 +/- 26% for MR. The time to maximal volume reduction was 8.0 +/- 4.4 months for FET, and 15.0 +/- 3.0 months for MR. The initial metabolic response correlated with the best volume response on MR (Spearman Rank P = 0.011). Deactivation of amino acid transport represents an early indicator of chemotherapy response in LGG. Response assessment based on MR only has to be reconsidered. The time window obtained from PET may assist for individual treatment decisions in LGG patients.

Topics: Adult; Antineoplastic Agents, Alkylating; Brain Neoplasms; Dacarbazine; Female; Fluorine Radioisotopes; Follow-Up Studies; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; Temozolomide; Time Factors; Tyrosine; Young Adult

The aim of the present study was to evaluate whether extended analyses of O-(2-18F-fluoroethyl)-L-tyrosine (FET) uptake kinetics provide results superior to those of standard tumor-to-background ratios in predicting tumor grade in patients with pretreated gliomas.. Dynamic 18F-FET PET studies (0-40 min after injection of 180 MBq of 18F-FET) were performed on 45 glioma patients with suspected tumor recurrence after multimodal treatment. For the standard method, tumoral maximal standardized uptake value (SUVmax) and the ratio to the background were derived from a summed image 20-40 min after injection. Dynamic data evaluation comprised several approaches: first, SUV within a 90% isocontour threshold (SUV90) and the respective ratio to the background calculated for each time frame between 5 and 40 min after injection; second, the time to peak analysis; and third, various parameters accounting for the individual time course of 18F-FET uptake. Results were correlated with the histopathologic findings of MRI/PET-guided stereotactic biopsies and were evaluated with respect to their discriminatory power to separate low- from high-grade tumors using receiver-operating characteristic (ROC) analyses.. The parameters taking into account the individual time course of 18F-FET uptake were able to differentiate low-grade from high-grade recurrent astrocytomas with high diagnostic accuracy, reaching the best differentiation with a sensitivity and specificity of 92% and an area under the ROC curve (AUC) of 0.94. For the other parameters, the respective values were considerably lower (time to peak: 85% sensitivity and 88% specificity; SUV90-to-background ratio for single-frame evaluation of the early-uptake phase: 100% sensitivity, 62% specificity, and 0.81 AUC). The lowest performance was provided by the standard method (SUVmax: 73% sensitivity, 54% specificity, and 0.60 AUC; SUVmax-to-background ratio: 62% sensitivity, 62% specificity, and 0.59 AUC). Time-activity curves (5-40 min after injection) slightly and steadily increased in tumor-free patients and in low-grade tumors, whereas high-grade tumors showed an early peak around 10-15 min after injection followed by a decrease.. This study has shown differences in the dynamics of 18F-FET uptake between recurrent low- and high-grade gliomas. Therefore, parameters addressing the different kinetic behaviors allow discrimination with high diagnostic power between these 2 prognostically different groups. Thus, the techniques introduced here are clearly superior to the yet most widely used standard method.

Topics: Adult; Algorithms; Brain; Brain Neoplasms; Computer Simulation; Female; Glioma; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Kinetics; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Neoplasm Recurrence, Local; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Tyrosine

Intracavitary radioimmunotherapy (RIT) offers an effective adjuvant therapeutic approach in patients with malignant gliomas. Since differentiation between recurrence and reactive changes following RIT has a critical impact on patient management, the aim of this study was to analyse the value of serial O-(2-[(18)F]fluoroethyl)-L: -tyrosine (FET) PET scans in monitoring the effects of this locoregional treatment.. Following conventional therapy, 24 glioma patients (5 WHO III, 19 WHO IV) underwent one to five RIT cycles with either (131)I-labelled (n=19) or (188)Re-labelled (n=5) anti-tenascin antibodies. Patients were monitored with serial FET PET scans (2-12 scans). For semiquantitative evaluation, maximal tumoural uptake (TU(max)) was evaluated and the ratio to background (BG) was calculated. Results of PET were correlated with histopathological findings (n=9) and long-term clinical follow-up for up to 87 months.. In seven tumour-free patients, PET revealed slightly increasing but homogeneous FET uptake surrounding the resection cavity with a peak up to 18 months following RIT (TU(max)/BG 2.07+/-0.25) but stable or decreasing values during further follow-up (last follow-up: TU(max)/BG 1.63+/-0.22). Seventeen patients developed regrowth of residual tumour/tumour recurrence showing additional nodular FET uptake (TU(max)/BG 2.79+/-0.53). A threshold value of 2.4 (TU(max)/BG) allowed best differentiation between recurrence and reactive changes (sensitivity 82%, specificity 100%).. FET PET is a sensitive tool for monitoring the effects of locoregional RIT. Homogeneous, slightly increasing FET uptake around the tumour cavity with a peak up to 18 months after RIT, followed by stable or decreasing uptake, points to benign, therapy-related changes. In contrast, nodular uptake is a reliable indicator of recurrence.

Topics: Adult; Brachytherapy; Brain Neoplasms; Female; Glioma; Humans; Male; Middle Aged; Positron-Emission Tomography; Prognosis; Radioimmunotherapy; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome; Tyrosine

The prognosis of patients with recurrent gliomas depends on reliable and early diagnosis of tumour recurrence after initial therapy. In this context, magnetic resonance imaging (MRI) and computed tomography (CT) often fail to differentiate between radiation- and tumour-induced contrast enhancement. Furthermore, absence of contrast enhancement, or even of 18F-fluorodeoxyglucose uptake in PET, does not exclude recurrence. The aim of this study was to establish the diagnostic value of O-(2-[18F]fluoroethyl)- L-tyrosine (FET) PET in recurrent gliomas.. Fifty-three patients with glioma (primary grading: 27=WHO grade IV, 16=grade III, 9=grade II, 1=grade I) and clinically suspected recurrence underwent FET PET scans 4-180 months after different treatment modalities. For semiquantitative evaluation, maximal SUV (SUVmax) and mean SUV within 80% and 70% isocontour thresholds (SUV80/SUV70) were evaluated and the respective ratios to the background (BG) were calculated. PET results were correlated with MRI/CT, clinical follow-up or biopsy findings.. All patients presented with FET uptake, of varying intensity, in the area of the primary tumour after initial therapy. In the 42 patients with confirmed recurrence, there was additional distinct focal FET uptake with significantly higher values compared with those in the 11 patients without clinical signs of recurrence and showing only low and homogeneous FET uptake at the margins of the resection cavity. With respect to tumour grading, there was a slight but non-significant increase from WHO II (SUVmax/BG: 2.53+/-0.28) to WHO III (SUVmax/BG: 2.84+/-0.49) and WHO IV (SUVmax/BG: 3.55+/-1.07) recurrence.. FET PET reliably distinguishes between post-therapeutic benign lesions and tumour recurrence after initial treatment of low- and high-grade gliomas.

Topics: Brain Neoplasms; Fluorine Radioisotopes; Glioma; Humans; Neoplasm Recurrence, Local; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome; Tyrosine

In glioma patients, differentiation between tumor progression (TP) and treatment-related changes (TRCs) remains challenging. Difficulties in classifying imaging alterations may result in a delay or an unnecessary discontinuation of treatment. PET using

Topics: Adult; Aged; Disease Progression; Female; Glioma; Humans; Male; Middle Aged; Positron-Emission Tomography; Retrospective Studies; Tyrosine; Young Adult

PET using

Topics: Adult; Aged; Brain Neoplasms; Female; Glioma; Humans; Male; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Preoperative Period; Tyrosine

Positron emission tomography (PET) using O-(2-[. Ten patients with untreated cerebral gliomas and one patient with a recurrent glioblastoma (GBM) were investigated by dynamic [. NaT (p = 0.05), tumor-to-brain ratios (TBR) of NaT (p = 0.02), NaNR (p = 0.003), and the ratio of NaT/NaR (p < 0.001) were significantly higher in IDH-mutated than in IDH-wild-type gliomas (n = 5 patients each) while NaR was significantly lower in IDH-mutated gliomas (p = 0.01). [. Sodium MRI appears to be more strongly related to the IDH mutational status than are [

Topics: Adult; Brain Neoplasms; Cohort Studies; Female; Fluorine Radioisotopes; Glioma; Humans; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Male; Middle Aged; Pilot Projects; Positron-Emission Tomography; Radiopharmaceuticals; Tumor Burden; Tyrosine

Quantitative parametric images of O-(2-[

Topics: Adult; Aged; Brain Mapping; Brain Neoplasms; Fluorine Radioisotopes; Glioma; Humans; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Tissue Distribution; Tyrosine; Young Adult

F-fluoroethyltyrosine (FET) is a well-established PET tracer for the imaging of cerebral gliomas. Recent studies reported interest in meningiomas. A study published by Cornelius et al concludes that FET PET may provide additional information for noninvasive grading of meningiomas. Indeed, the combination of tumor background ratio with a cutoff value of 2.3 associated with time activity curve pattern slightly improved the differentiation of high-grade from low-grade meningiomas (accuracy, 92%; P = 0.001). We present the case of a 75-year-old man that underlined the need to confirm the performance of these tools (curve pattern, tumor background ratios) to characterize meningiomas.

Topics: Aged; Biological Transport; Glioma; Humans; Kinetics; Male; Meningeal Neoplasms; Meningioma; Positron-Emission Tomography; Radioactive Tracers; Tyrosine

The aim of this study was to analyze the robustness and diagnostic value of different compartment models for dynamic

Topics: Aged; Antineoplastic Agents; Brain Neoplasms; Carbon; Female; Glioma; Heavy Ion Radiotherapy; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Models, Statistical; Neoplasm Grading; Neoplasm Recurrence, Local; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; Survival Analysis; Temozolomide; Tyrosine

Most high-grade gliomas (HGG) recur after initial multimodal therapy and re-irradiation (Re-RT) has been shown to be a valuable re-treatment option in selected patients. We evaluated the prognostic value of dynamic time-to-peak analysis and early static summation images in O-(2-

Topics: Adolescent; Adult; Aged; Antineoplastic Agents, Immunological; Bevacizumab; Brain Neoplasms; Female; Glioma; Humans; Karnofsky Performance Status; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Nonlinear Dynamics; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Re-Irradiation; Survival Analysis; Time Factors; Tyrosine; Young Adult

Positron emission tomography (PET) using O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) is a well-established method for the diagnostics of brain tumors. This study investigates reproducibility of (18)F-FET uptake kinetics in rat gliomas and the influence of the frequently used dexamethasone (Dex) therapy.. F98 glioma or 9L gliosarcoma cells were implanted into the striatum of 31 Fischer rats. After 10-11 days of tumor growth, the animals underwent dynamic PET after injection of (18)F-FET (baseline). Thereafter, animals were divided into a control group and a group receiving Dex injections, and all animals were reinvestigated 2 days later. Tumor-to-brain ratios (TBR) of (18)F-FET uptake (18-61 min p.i.) and the slope of the time-activity-curves (TAC) (18-61 min p.i.) were evaluated using a Volume-of-Interest (VOI) analysis. Data were analyzed by two-way repeated measures ANOVA and reproducibility by the intraclass correlation coefficient (ICC).. The slope of the tumor TACs showed high reproducibility with an ICC of 0.93. A systematic increase of the TBR in the repeated scans was noted (3.7 ± 2.8 %; p < 0.01), and appeared to be related to tumor growth as indicated by a significant correlation of TBR and tumor volume (r = 0.77; p < 0.0001). After correction for tumor growth TBR showed high longitudinal stability with an ICC of 0.84. Dex treatment induced a significant decrease of the TBR (-8.2 ± 6.1 %; p < 0.03), but did not influence the slope of the tumor TAC.. TBR of (18)F-FET uptake and tracer kinetics in brain tumors showed high longitudinal stability. Dex therapy may induce a minor decrease of the TBR; this needs further investigation.

Topics: Animals; Biological Transport; Brain Neoplasms; Dexamethasone; Disease Models, Animal; Glioma; Kinetics; Male; Positron-Emission Tomography; Rats; Reproducibility of Results; Tyrosine

O-(2-[18F]-fluoroethyl)-L-tyrosine positron emission tomography ((18)F-FET-PET) imaging is applied for tumor grading, prognostic stratification, and diagnosis of tumor recurrence, especially in high-grade gliomas. Experience with (18)F-FET-PET imaging in low-grade gliomas is limited. Therefore, the objective of the present study was to assess (18)F-FET-PET tracer uptake in low-grade gliomas and to investigate possible correlations with contrast enhancement in magnetic resonance imaging (MRI) and histopathology.. A total of 65 patients (29 female, 36 male, median age 38 years) with newly diagnosed or recurrent low-grade gliomas for whom preoperative MRI and (18)F-FET-PET imaging were available were included. Tumor entity, tumor location, as well as histopathology (isocitrate dehydrogenase [IDH] 1/2 mutation, Ki67, p53, oligodendroglial differentiation, 1p19q codeletion), and progression-free survival were assessed. (18)F-FET-PET images were acquired and fused to MRI (T2-weighted fluid-attenuated inversion recovery) and tumor volume was measured in areas with a tumor-to-background ratio >1.3, >1.6, and >2.0 and in MRI.. PET tracer uptake was observed in 78.5% of all World Health Organization Grade I and II tumors. (18)F-FET uptake showed a high negative predictive value for oligodendroglial components and for 1p19q codeletion. No further significant correlation between histologic features, progression-free survival, or IDH1/2 mutation status and tracer uptake was observed.. We found that 78.5% of low-grade gliomas do show elevated tracer uptake in (18)F-FET-PET imaging. Low-grade glioma without tracer uptake exclude oligodendroglial differentiation and 1p19q codeletion. Further differentiation between molecular subtypes is not possible with static (18)F-FET-PET. No correlation of progression-free survival to tracer uptake and IDH1/2-mutation status was observed.

Topics: Adult; Biomarkers, Tumor; Brain; Brain Neoplasms; Disease-Free Survival; Female; Glioma; Humans; Kaplan-Meier Estimate; Magnetic Resonance Imaging; Male; Neoplasm Grading; Neoplasm Recurrence, Local; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Retrospective Studies; Sensitivity and Specificity; Tumor Burden; Tyrosine

We sought to assess the impact of amino-acid (18)F-fluoro-ethyl-tyrosine (FET) positron emission tomography (PET) on the volumetric target definition for radiation therapy of high-grade glioma versus the current standard using MRI alone. Specifically, we investigated the influence of tumor grade, MR-defined tumor volume, and the extent of surgical resection on PET positivity.. Fifty-four consecutive high-grade glioma patients (World Health Organization grades III-IV) with confirmed histology were scanned using FET-PET/CT and T1 and T2/fluid attenuated inversion recovery MRI. Gross tumor volume and clinical target volumes (CTVs) were defined in a blinded fashion based on MRI and subsequently PET, and volumetric analysis was performed. The extent of the surgical resection was reviewed using postoperative MRI.. Overall, for ∼ 90% of the patients, the PET-positive volumes were encompassed by T1 MRI with contrast-defined tumor plus a 20-mm margin. The tumor volume defined by PET was larger for glioma grade IV (P < .001) and smaller for patients with more extensive surgical resection (P = .004). The margin required to be added to the MRI-defined tumor in order to fully encompass the FET-PET positive volume tended to be larger for grade IV tumors (P = .018).. With an unchanged CTV margin and by including FET-PET for gross tumor volume definition, the CTV will increase moderately for most patients, and quite substantially for a minority of patients. Patients with grade IV glioma were found to be the primary candidates for PET-guided radiation therapy planning.

Topics: Adult; Aged; Aged, 80 and over; Brain Neoplasms; Glioma; Humans; Magnetic Resonance Imaging; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Tyrosine; Young Adult

Histopathological examination is the standard for grading and determination of diagnosis in intrinsic brain tumors though the possibility of malignization and tumor heterogeneity always bears the possibility of tumor under-grading or misjudgement regarding the estimation of prognosis. The aim of the present study was to evaluate the use of (18)F-FET-PET (FET-PET) for the grading and estimation of prognosis in newly diagnosed patients with intracranial gliomas in a clinical setting.. Patients who were treated for a newly diagnosed intracranial glioma between January 2007 and May 2012, and had a preoperative FET-PET and MRI scan between were included. The ratio of counts in a tumor VOI (volume of interest) with maximum uptake to the respective counts in a background VOI was calculated to provide the tumor-to-normal (T/N) ratio. The clinical and histopathological data (tumor grading, pre- and postoperative neurological status, Karnofsky Performance Status Scale scores, and overall survival rates) were recorded.. One hundred fifty-two patients (39 WHO II, 26 WHO III, 87 WHO IV) were included. The median T/N ratio was 2.81 (1.1-8.1). The median T/N ratio of low-grade glioma patients was 1.65 (1.1-3.7), and 3.14 (1.61-8.1, p<0.001) in high-grade glioma patients. The median survival for patients with WHO III tumors was 22.8 months (95% CI: 15.87%-NA) and 13.23 months (95% CI: 10.83-15.6.%) for patients with WHO IV tumors (p=0.0001). For T/N≤1.6, no deaths were recorded; for 1.63, median survival was 14.0 months (95% CI: 11.7-16.2%, p<0.001). The test of the maximally selected log-rank statistic resulted in a T/N ratio of 1.88 as the cut-off value, with the greatest difference in overall survival between patients with longer and shorter survival. The ROC curve for differentiation of low- vs. high-grade tumors with regard to the T/N ratio showed an area under the curve (AUC) of 0.903. Regarding the prognostic validity for overall survival ROC-curves for 12-month, 24-month and 48-month survival display a higher validity for the WHO-classification than for the imaging modalities though with an AUC of 0.847 for the 48-month survival T/N ratio and MRI contrast-enhancement have a high prognostic value as well.. Our study suggests that FET-PET can predict prognosis and survival in patients harboring intracranial gliomas and serves as a valuable tool to supplement the established clinical and histopathological parameters.

Topics: Adult; Aged; Area Under Curve; Brain Neoplasms; Female; Follow-Up Studies; Glioma; Humans; Male; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; ROC Curve; Tyrosine

We aimed to evaluate the diagnostic potential of dual-time-point imaging with positron emission tomography (PET) using O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) for non-invasive grading of cerebral gliomas compared with a dynamic approach.. Thirty-six patients with histologically confirmed cerebral gliomas (21 primary, 15 recurrent; 24 high-grade, 12 low-grade) underwent dynamic PET from 0 to 50 min post-injection (p.i.) of (18)F-FET, and additionally from 70 to 90 min p.i. Mean tumour-to-brain ratios (TBRmean) of (18)F-FET uptake were determined in early (20-40 min p.i.) and late (70-90 min p.i.) examinations. Time-activity curves (TAC) of the tumours from 0 to 50 min after injection were assigned to different patterns. The diagnostic accuracy of changes of (18)F-FET uptake between early and late examinations for tumour grading was compared to that of curve pattern analysis from 0 to 50 min p.i. of (18)F-FET.. The diagnostic accuracy of changes of the TBRmean of (18)F-FET PET uptake between early and late examinations for the identification of HGG was 81% (sensitivity 83%; specificity 75%; cutoff - 8%; p < 0.001), and 83% for curve pattern analysis (sensitivity 88%; specificity 75%; p < 0.001).. Dual-time-point imaging of (18)F-FET uptake in gliomas achieves diagnostic accuracy for tumour grading that is similar to the more time-consuming dynamic data acquisition protocol.. • Dual-time-point imaging is equivalent to dynamic FET PET for grading of gliomas. • Dual-time-point imaging is less time consuming than dynamic FET PET. • Costs can be reduced due to higher patient throughput. • Reduced imaging time increases patient comfort and sedation might be avoided. • Quicker image interpretation is possible, as no curve evaluation is necessary.

Topics: Adult; Aged; Brain Neoplasms; Female; Glioma; Humans; Male; Middle Aged; Neoplasm Grading; Physical Examination; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity; Tyrosine

We evaluated the diagnostic value of static and dynamic O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) PET parameters in patients with progressive or recurrent glioma.. We retrospectively analyzed 132 dynamic (18)F-FET PET and conventional MRI scans of 124 glioma patients (primary World Health Organization grade II, n = 55; grade III, n = 19; grade IV, n = 50; mean age, 52 ± 14 y). Patients had been referred for PET assessment with clinical signs and/or MRI findings suggestive of tumor progression or recurrence based on Response Assessment in Neuro-Oncology criteria. Maximum and mean tumor/brain ratios of (18)F-FET uptake were determined (20-40 min post-injection) as well as tracer uptake kinetics (ie, time to peak and patterns of the time-activity curves). Diagnoses were confirmed histologically (95%) or by clinical follow-up (5%). Diagnostic accuracies of PET and MR parameters for the detection of tumor progression or recurrence were evaluated by receiver operating characteristic analyses/chi-square test.. Tumor progression or recurrence could be diagnosed in 121 of 132 cases (92%). MRI and (18)F-FET PET findings were concordant in 84% and discordant in 16%. Compared with the diagnostic accuracy of conventional MRI to diagnose tumor progression or recurrence (85%), a higher accuracy (93%) was achieved by (18)F-FET PET when a mean tumor/brain ratio ≥2.0 or time to peak <45 min was present (sensitivity, 93%; specificity, 100%; accuracy, 93%; positive predictive value, 100%; P < .001).. Static and dynamic (18)F-FET PET parameters differentiate progressive or recurrent glioma from treatment-related nonneoplastic changes with higher accuracy than conventional MRI.

Topics: Brain Neoplasms; Disease Progression; Female; Glioma; Humans; Male; Middle Aged; Positron-Emission Tomography; Retrospective Studies; Sensitivity and Specificity; Tyrosine

O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) is an established tracer for brain tumour imaging. (18)F-FET kinetics in gliomas appear to have potential for tumour grading, but the mechanisms remain unclear. The aim of this study was to explore the relationship between regional cerebral blood flow (rCBF) as measured by arterial spin labelling MRI and the kinetic behaviour of (18)F-FET PET in cerebral gliomas.. Twenty patients with cerebral gliomas were investigated using arterial spin labelling MRI and dynamic (18)F-FET PET. Time-activity curves (TACs) of (18)F-FET uptake were analysed in 33 different tumour regions. The slopes of TAC during the early (0-5 min; slopeup) and late phases of tracer uptake (17-50 min; slopedown) were fitted using linear regression lines. In addition, TACs of each lesion were assigned to different curve patterns. Furthermore, we calculated tumour-to-brain ratios of (18)F-FET uptake. The relationship between (18)F-FET parameters and rCBF was determined.. (18)F-FET uptake in the early phase (slopeup) showed a significant correlation with rCBF (r=0.4; P=0.02). In contrast, both slopedown and TAC patterns showed no significant correlation with rCBF. Furthermore, a significant correlation was found between rCBF and tumour-to-brain ratio (r=0.53; P=0.002).. There is a relationship between rCBF and (18)F-FET uptake in cerebral gliomas in the initial uptake phase, but the kinetic behaviour of (18)F-FET uptake in the late phase is not significantly influenced by rCBF. Thus, the differential kinetic pattern of (18)F-FET uptake in high-grade and low-grade gliomas appears to be determined by factors other than rCBF.

Topics: Adult; Aged; Biological Transport; Brain Neoplasms; Cerebrovascular Circulation; Female; Glioma; Humans; Kinetics; Male; Middle Aged; Positron-Emission Tomography; Tyrosine

To evaluate the prognostic value of O-(2-[(18)F]fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) uptake intensity in World Health Organisation (WHO) tumor grade II-IV gliomas.. We studied 28 patients with WHO tumor grade II-IV gliomas who were referred to our department for radiation therapy. We acquired a FET-PET in all patients, as well as magnetic resonance imaging (MRI) of the brain consisting of at least T2-weighted imaging, flair and pre- and post-contrast T1-weighted imaging. SUVmax was measured and the tumor-to-brain uptake ratio (TBR) of all lesions was calculated based on the SUVmax (TBRmax) or SUVmean (TBRmean) of the contralateral healthy tissue. For this study, volumes were calculated using MRI alone, MRI + the volume with a SUVmax on FET-PET ≥ 2.2 as well as MRI + the volume with an uptake of at least 40 % of the SUVmax.. Tumor volumes were a median (range) of 88.6 (2.6-467.4) ml (MRI alone), 84.2 (2.8-474.4) ml (MRI + SUVmax on FET-PET ≥ 2.2) and 101.5 (4.0-512.1) ml (MRI + FET-PET uptake ≥ 40 % SUVmax), respectively. TBR-SUVmean was 2.36 (1.46-4.08); TBR-SUVmax was 1.71 (0.97-2.85). During a follow-up of 18.7 (2.5-36.1) months after FET-PET, 12 patients died of malignant glioma. Patients with a SUVmax ≥ 2.6 had a significantly worse tumor-related mortality (p = 0.005) and progression-free survival (p = 0.038) than those with a lower SUVmax. Multivariate analysis showed that WHO tumor grade (p = 0.001) and SUVmax ≥ 2.6 (p < 0.001) were independent predictors for tumor-related mortality, but not tumor volume or TBRmax or TBRmean. SUVmax ≥ 2.6 (p = 0.007) and being treated for a recurrence rather than for a primary tumor manifestation (p = 0.014) were predictors for progression-free survival, but not TBRmax or TBRmean.. In this heterogeneous patient population, higher tracer uptake in FET-PET appears to be associated with a worse tumor-related mortality and a shorter duration of the disease-free interval.

Topics: Adolescent; Adult; Aged; Brain; Brain Neoplasms; Disease-Free Survival; Female; Glioma; Humans; Kaplan-Meier Estimate; Magnetic Resonance Imaging; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Time Factors; Tyrosine; Young Adult

Low-grade gliomas (LGGs) may harbor malignant foci, which are characterized by increased tumor cellularity and angiogenesis. We used diffusion-weighted MR imaging (apparent diffusion coefficient [ADC]) and PET with the amino acid O-(2-(18)F-fluorethyl)-L-tyrosine ((18)F-FET) to search for focal changes of diffusion (ADC) and amino acid uptake and to investigate whether focal changes in these parameters colocalize within LGGs.. We retrospectively selected 18 patients with nonenhancing LGG. All patients had undergone (18)F-FET PET and MR imaging for preoperative evaluation or for therapy monitoring in recurrent or progressive LGG. Region-of-interest analysis was performed to compare (18)F-FET uptake and ADC values in areas with focal intratumoral maximum metabolic activity and diffusion restriction and between tumor and normal brain. (18)F-FET uptake was normalized to the mean cerebellar uptake (ratio). ADC values were also compared with the (18)F-FET uptake on a voxel-by-voxel basis across the whole tumor.. The mean focal maximum (mean ± SD, 1.69 ± 0.85) and global (18)F-FET uptake in tumors (1.14 ± 0.41) exceeded that of normal cortex (0.85 ± 0.09) and cerebrospinal fluid (0.82 ± 0.20). ADC values in the area with most restricted diffusion (1.07 ± 0.22 × 10(-3) mm(2)/s) and in the whole tumor (1.38 ± 0.27 × 10(-3) mm(2)/s) were in the range between normal cortex (0.73 ± 0.06 × 10(-3) mm(2)/s) and cerebrospinal fluid (2.84 ± 0.09 × 10(-3) mm(2)/s). (18)F-FET uptake did not correlate with corresponding (colocalizing) ADC values, either in the area with focal maximum metabolic activity or in the area with most restricted diffusion or in the whole tumor.. There is no congruency between (18)F-FET uptake and diffusivity in nonenhancing LGG. Diffusion restriction in these tumors most likely represents changes in brain and tumor cell densities as well as alteration of water distribution and is probably not directly correlated with the density of tumor cells.

Topics: Adult; Aged; Amino Acids; Brain Neoplasms; Cerebellar Neoplasms; Cerebellum; Diffusion; Diffusion Magnetic Resonance Imaging; Female; Glioma; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; Tyrosine

Therapy monitoring of glioma after stereotactic iodine-125 brachytherapy (SBT) remains challenging because posttherapeutic changes in magnetic resonance imaging can mimic tumor progression. We evaluated the prognostic value of serial [18F]fluoroethyltyrosine (FET)-positron emission tomographic (PET) scans for therapy monitoring of high-grade glioma (HGG) after SBT. Thirty-three patients with recurrent HGG were included. Serial FET-PET scans were performed prior to therapeutic intervention and at 3-month intervals during the first year after SBT. FET-PET evaluation was performed by both conventional data analysis and kinetic analysis. Prognostic factors were obtained from proportional hazard models. Median local progression-free survival (LPFS) was 11.1 months. Maximal standardized background uptake value (SUVmax/BG) and biologic tumor volume (BTV) differentiated accurately between therapeutic effects and local tumor progression at the 6-month and subsequent examinations. Increasing uptake kinetics at baseline (p < .05) and during follow-up (p < .01) were stringently associated with a longer LPFS. Early increase in FET uptake after SBT is not unequivocally associated with tumor progression; it might be induced by reactive changes and could easily lead to a misclassification of the tumor status (pseudoprogression). Six months after SBT (or later), however, increased SUVmax/BG and BTV values are associated with a worse prognosis. Multivariate analysis stresses the prognostic importance of dynamic studies.

Topics: Brachytherapy; Disease-Free Survival; Glioma; Humans; Iodine; Magnetic Resonance Imaging; Positron-Emission Tomography; Tyrosine

PET using O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) allows improved imaging of tumor extent of cerebral gliomas in comparison to MRI. In experimental brain infarction and hematoma, an unspecific accumulation of (18)F-FET has been detected in the area of reactive astrogliosis which is a common cellular reaction in the vicinity of cerebral gliomas. The aim of this study was to investigate possible (18)F-FET uptake in the area of reactive gliosis in the vicinity of untreated and irradiated rat gliomas.. F98-glioma cells were implanted into the caudate nucleus of 33 Fisher CDF rats. Sixteen animals remained untreated and in 17 animals the tumor was irradiated by Gamma Knife 5-8 days after implantation (2/50 Gy, 3/75 Gy, 6/100 Gy, 6/150 Gy). After 8-17 days of tumor growth the animals were sacrificed following injection of (18)F-FET. Brains were removed, cut in coronal sections and autoradiograms of (18)F-FET distribution were produced and compared with histology (toluidine blue) and reactive astrogliosis (GFAP staining). (18)F-FET uptake in the tumors and in areas of reactive astrocytosis was evaluated by lesion to brain ratios (L/B).. Large F98-gliomas were present in all animals showing increased (18)F-FET-uptake which was similar in irradiated and non-irradiated tumors (L/B: 3.9 ± 0.8 vs. 4.0 ± 1.3). A pronounced reactive astrogliosis was noted in the vicinity of all tumors that showed significantly lower (18)F-FET-uptake than the tumors (L/B: 1.5 ± 0.4 vs. 3.9 ± 1.1). The area of (18)F-FET-uptake in the tumor was congruent with histological tumor extent in 31/33 animals. In 2 rats irradiated with 150 Gy, however, high (18)F-FET uptake was noted in the area of astrogliosis which led to an overestimation of the tumor size.. Reactive astrogliosis in the vicinity of gliomas generally leads to only a slight (18)F-FET-enrichment that appears not to affect the correct definition of tumor extent for treatment planning.

Topics: Animals; Biological Transport; Brain; Brain Neoplasms; Cell Line, Tumor; False Positive Reactions; Glioma; Gliosis; Male; Positron-Emission Tomography; Rats; Tyrosine

Modern radiotherapy (RT) techniques such as stereotactic RT, intensity-modulated RT, or particle irradiation allow local dose escalation with simultaneous sparing of critical organs. Several trials are currently investigating their benefit in glioma reirradiation and boost irradiation. Target volume definition is of critical importance especially when steep dose gradient techniques are employed. In this manuscript we investigate the impact of O-(2-(F-18)fluoroethyl)-l-tyrosine-positron emission tomography/computer tomography (FET-PET/CT) on target volume definition in low and high grade glioma patients undergoing either first or re-irradiation with particles.. We investigated volumetric size and uniformity of magnetic resonance imaging (MRI)- vs. FET-PET/CT-derived gross tumor volumes (GTVs) and planning target volumes (PTVs) of 41 glioma patients. Clinical cases are presented to demonstrate potential benefits of integrating FET-PET/CT-planning into daily routine.. Integrating FET-uptake into the delineation of GTVs yields larger volumes. Combined modality-derived PTVs are significantly enlarged in high grade glioma patients and in case of primary RT. The congruence of MRI and FET signals for the identification of glioma GTVs is poor with mean uniformity indices of 0.39. MRI-based PTVs miss 17% of FET-PET/CT-based GTVs. Non significant alterations were detected in low grade glioma patients and in those undergoing reirradiation.. Target volume definition for malignant gliomas during initial RT may yield significantly differing results depending upon the imaging modality, which the contouring process is based upon. The integration of both MRI and FET-PET/CT may help to improve GTV coverage by avoiding larger incongruences between physical and biological imaging techniques. In low grade gliomas and in cases of reirradiation, more studies are needed in order to investigate a potential benefit of FET-PET/CT for planning of RT.

Topics: Adult; Aged; Brain Neoplasms; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Tomography, X-Ray Computed; Tyrosine; Young Adult

In patients with low-grade glioma (LGG) of World Health Organization (WHO) grade II, early detection of progression to WHO grade III or IV is of high clinical importance because the initiation of a specific treatment depends mainly on the WHO grade. In a significant number of patients with LGG, however, information on tumor activity and malignant progression cannot be obtained on the basis of clinical or conventional MR imaging findings only. We here investigated the potential of O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET to noninvasively detect malignant progression in patients with LGG.. Twenty-seven patients (mean age ± SD, 44 ± 15 y) with histologically proven LGG (WHO grade II) were investigated longitudinally twice using dynamic (18)F-FET PET and routine MR imaging. Initially, MR imaging and PET scans were performed, and diagnosis was confirmed on the basis of biopsy. Subsequently, PET scans were obtained when clinical findings or contrast-enhanced MR imaging suggested malignant progression. Maximum and mean tumor-to-brain ratios (20-40 min after injection) (TBRmax and TBRmean, respectively) of (18)F-FET uptake as well as tracer uptake kinetics (i.e., time to peak [TTP] and patterns of the time-activity curves) were determined. The diagnostic accuracy of imaging parameters for the detection of malignant progression was evaluated by receiver-operating-characteristic analyses and by Fisher exact test for 2 × 2 contingency tables.. In patients with histologically proven malignant progression toward WHO grade III or IV (n = 18), TBRmax and TBRmean increased significantly, compared with baseline (TBRmax, 3.8 ± 1.0 vs. 2.4 ± 1.0; TBRmean, 2.2 ± 0.3 vs. 1.6 ± 0.6; both P < 0.001), whereas TTP decreased significantly (median TTP, 35 vs. 23 min; P < 0.001). Furthermore, time-activity curve patterns changed significantly in 10 of 18 patients (P < 0.001). The combined analysis of (18)F-FET PET parameters (i.e., changes of TBRmax, TTP, or time-activity curve pattern) yielded a significantly higher diagnostic accuracy for the detection of malignant progression than changes of contrast enhancement in MR imaging (accuracy, 81% vs. 63%; P = 0.003).. Both tumor-to-brain ratio and kinetic parameters of (18)F-FET PET uptake provide valuable diagnostic information for the noninvasive detection of malignant progression of LGG. Thus, repeated (18)F-FET PET may be helpful for further treatment decisions.

Topics: Adolescent; Adult; Biological Transport; Child; Disease Progression; Female; Glioma; Humans; Kinetics; Male; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Regression Analysis; Tyrosine; Young Adult

To assess the sensitivity and specificity of [(18)F]-fluoro-ethyl-l-tyrosine ((18)F-FET) PET in brain tumors and various non-neoplastic neurologic diseases.. We retrospectively evaluated (18)F-FET PET scans from 393 patients grouped into 6 disease categories according to histology (n = 299) or distinct MRI findings (n = 94) (low-grade/high-grade glial/nonglial brain tumors, inflammatory lesions, and other lesions). (18)F-FET PET was visually assessed as positive or negative. Maximum lesion-to-brain ratios (LBRs) were calculated and compared with MRI contrast enhancement (CE), which was graded visually on a 3-point scale (no/moderate/intense).. Sensitivity and specificity for the detection of brain tumor were 87% and 68%, respectively. Significant differences in LBRs were detected between high-grade brain tumors (LBR, 2.04 ± 0.72) and low-grade brain tumors (LBR, 1.52 ± 0.70; P < .001), as well as among inflammatory (LBR, 1.66 ± 0.33; P = .056) and other brain lesions (LBR, 1.10 ± 0.37; P < .001). Gliomas (n = 236) showed (18)F-FET uptake in 80% of World Health Organization (WHO) grade I, 79% of grade II, 92% of grade III, and 100% of grade IV tumors. Low-grade oligodendrogliomas, WHO grade II, had significantly higher (18)F-FET uptakes than astrocytomas grades II and III (P = .018 and P = .015, respectively). (18)F-FET uptake showed a strong association with CE on MRI (P < .001) and was also positive in 52% of 157 nonglial brain tumors and nonneoplastic brain lesions.. (18)F-FET PET has a high sensitivity for the detection of high-grade brain tumors. Its specificity, however, is limited by passive tracer influx through a disrupted blood-brain barrier and (18)F-FET uptake in nonneoplastic brain lesions. Gliomas show specific tracer uptake in the absence of CE on MRI, which most likely reflects biologically active tumor.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood-Brain Barrier; Brain Neoplasms; Female; Fluorodeoxyglucose F18; Follow-Up Studies; Glioma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Retrospective Studies; Sensitivity and Specificity; Tyrosine; Young Adult

The aim of the present study is to determine new positron emission tomography (PET) imaging-related factors predictive of progression-free survival as well as survival in patients with recurrent malignant glioma (MG) prior to and after re-irradiation. Fifty-six patients with recurrent MG who underwent re-irradiation treatment and pretherapeutic dynamic [(18)F]-fluoroethyl-L-tyrosine (FET)-PET scan were retrospectively analyzed. The prognostic value of different parameters, such as biological tumor volume, maximal tumor uptake (SUV(max)/BG), mean tumor uptake (SUV(mean)/BG), as well as uptake kinetics, was evaluated. [(18)F]FET uptake kinetics was classified according to a five-point rating as category G(1-2) (strongly/mainly increasing kinetics), G(3) (mixed 1:1), or G(4-5) (mainly/strongly decreasing kinetics). Patients within the pretherapeutic kinetic group G(4-5) had significantly worse survival than the other two groups (p = 0.01). Multivariate analysis revealed that histologic grade, Karnofsky Performance Score (KPS), and kinetic group were independent significant predictors for survival after re-irradiation. The uptake kinetics of [(18)F]FET-PET is an independent determinant of overall and to a lesser extent also progression-free survival. Thus, [(18)F]FET-PET kinetics may provide valuable additional prognostic information for treatment decisions.

Topics: Adolescent; Adult; Aged; Brain Neoplasms; Female; Fluorodeoxyglucose F18; Follow-Up Studies; Glioma; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Retrospective Studies; Salvage Therapy; Survival Rate; Tyrosine; Young Adult

The present study focuses on a micro-PET/CT application to be used for experimental Boron Neutron Capture Therapy (BNCT), which integrates, in the same frame, micro-CT derived anatomy and PET radiotracer distribution. Preliminary results have demonstrated that (18)F-fluoroethyl-tyrosine (FET)/PET allows the identification of the extent of cerebral lesions in F98 tumor bearing rat. Neutron autoradiography and α-spectrometry on axial tissues slices confirmed the tumor localization and extraction, after the administration of fructose-boronophenylalanine (BPA). Therefore, FET-PET approach can be used to assess the transport, the net influx, and the accumulation of FET, as an aromatic amino acid analog of BPA, in experimental animal model. Coregistered micro-CT images allowed the accurate morphological localization of the radiotracer distribution and its potential use for experimental BNCT.

Topics: Animals; Boron Neutron Capture Therapy; Brain Neoplasms; Disease Models, Animal; Glioma; Multimodal Imaging; Positron-Emission Tomography; Rats; Tomography, X-Ray Computed; Tyrosine

L-[methyl-(11)C]methionine (MET)-positron emission tomography (PET) has a high sensitivity and specificity for imaging of gliomas and metastatic brain tumors. The short half-life of (11)C (20 minutes) limits the use of MET-PET to institutions with onsite cyclotron. O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) is labeled with (18)F (half-life, 120 minutes) and could be used much more broadly. This study compares the uptake of FET and MET in gliomas and metastases, as well as treatment-induced changes. Furthermore, it evaluates the gross tumor volume (GTV) of gliomas defined on PET and magnetic resonance imaging (MRI).. We examined 42 patients with pretreated gliomas (29 patients) or brain metastases (13 patients) prospectively by FET- and MET-PET on the same day. Uptake of FET and MET was quantified by standardized uptake values. Imaging contrast was assessed by calculating lesion-to-gray matter ratios. Tumor extension was quantified by contouring GTV in 17 patients with brain gliomas. Gross tumor volume on PET was compared with GTV on MRI. Sensitivity and specificity of MET- and FET-PET for differentiation of viable tumor from benign changes were evaluated by comparing the PET result with histology or clinical follow-up.. There was a strong linear correlation between standardized uptake values calculated for both tracers in cortex and lesions: r = 0.78 (p = 0.001) and r = 0.84 (p < 0.001), respectively. Image contrast was similar for MET- and FET-PET (lesion-to-gray matter ratios of 2.36 ± 1.01 and 2.33 ± 0.77, respectively). Mean GTV in 17 glioma patients was not significantly different on MET- and FET-PET. Both MET- and FET-PET delineated tumor tissue outside of MRI changes. Both tracers provided differentiated tumor tissue and treatment-related changes with a sensitivity of 91% at a specificity of 100%.. O-(2-[(18)F]fluoroethyl)-L-tyrosine-PET and MET-PET provide comparable diagnostic information on gliomas and brain metastases. Like MET-PET, FET-PET can be used for differentiation of residual or recurrent tumor from treatment-related changes/pseudoprogression, as well as for delineation of gliomas.

Topics: Brain; Brain Neoplasms; Glioma; Humans; Magnetic Resonance Imaging; Methionine; Neoplasm Recurrence, Local; Neoplasm, Residual; Positron-Emission Tomography; Prospective Studies; Sensitivity and Specificity; Time Factors; Tumor Burden; Tyrosine

The objective of this study was to compare MRI response assessment with metabolic O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET response evaluation during antiangiogenic treatment in patients with recurrent high-grade glioma (rHGG).. Eleven patients with rHGG were treated biweekly with bevacizumab-irinotecan. MR images and (18)F-FET PET scans were obtained at baseline and at follow-up 8-12 wk after treatment onset. MRI treatment response was evaluated by T1/T2 volumetry according to response assessment in neurooncology (RANO) criteria. For (18)F-FET PET evaluation, an uptake reduction of more than 45% calculated with a standardized uptake value of more than 1.6 was defined as a metabolic response (receiver-operating-characteristic curve analysis). MRI and (18)F-FET PET volumetry results and response assessment were compared with each other and in relation to progression-free survival (PFS) and overall survival (OS).. At follow-up, MR images showed partial response in 7 of 11 patients (64%), stable disease in 2 of 11 patients (18%), and tumor progression in 2 of 11 patients (18%). In contrast, (18)F-FET PET revealed 5 of 11 metabolic responders (46%) and 6 of 11 nonresponders (54%). MRI and (18)F-FET PET showed that responders survived significantly longer than did nonresponders (10.24 vs. 4.1 mo, P = 0.025, and 7.9 vs. 2.3 mo, P = 0.015, respectively). In 4 patients (36.4%), diagnosis according to RANO criteria and (18)F-FET PET was discordant. In these cases, PET was able to detect tumor progression earlier than was MRI.. In rHGG patients undergoing antiangiogenic treatment, (18)F-FET PET seems to be predictive for treatment failure in that it contributes important information to response assessment based solely on MRI and RANO criteria.

Topics: Adult; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Astrocytoma; Bevacizumab; Brain Neoplasms; Camptothecin; Combined Modality Therapy; Disease-Free Survival; Female; Glioma; Humans; Image Processing, Computer-Assisted; Irinotecan; Magnetic Resonance Imaging; Male; Middle Aged; Nervous System Diseases; Positron-Emission Tomography; Postoperative Complications; Predictive Value of Tests; Radiopharmaceuticals; Retrospective Studies; Survival Analysis; Treatment Failure; Tyrosine; Ultrasonography

The aims of this study were to investigate and categorize peritumoral fiber tract alterations while considering changes in metabolism and integrity of fiber structures using multimodal neuroimaging-that is, PET with O-(2-(18)F-fluoroethyl)-l-tyrosine and diffusion tensor imaging evaluated by fiber density mapping-and to correlate categories of fiber alterations with preoperative neurologic deficits and postoperative course.. We examined 26 patients with cerebral gliomas. Fiber density data were used to segment peritumoral fiber structures and were coregistered to anatomic MR images and PET data. Fiber density and O-(2-(18)F-fluoroethyl)-l-tyrosine uptake values were evaluated as ipsilateral-to-contralateral ratios. Four metabolic categories were defined on the basis of O-(2-(18)F-fluoroethyl)-l-tyrosine values: tumor-infiltrated tissue, reactive tissue (astrogliosis and microglial activation), normal brain tissue, and tissue with attenuated amino acid metabolism. Fiber density values were grouped in 3 categories for structural integrity: compressed, normal, and attenuated fibers.. We evaluated and classified 103 peritumoral fiber structures with 10 patterns of fiber tract alterations. Fiber structures in tumor-infiltrated, reactive, and normal brain tissue showed compressed fibers, displaced fibers, and (partly) destroyed fibers, respectively. Attenuated amino acid metabolism was associated only with attenuated fiber density. Thirteen patients showed white matter-related neurologic deficits (paresis, hypoesthesia, aphasia, or anopia) as initial symptoms. Three patients showed tumor infiltration in the corresponding fiber tracts; all the others had reactive or normal brain tissue. Fiber structures were compressed or attenuated but not normal. The 3 patients with tumor infiltration in the corresponding fiber tracts and 1 with compressed fibers in normal brain showed no improvements or worsening of the deficits in the postoperative course. Eight patients with the corresponding fiber tracts in reactive or normal brain areas showed improvement of deficits. One patient underwent biopsy only.. Our multimodal neuroimaging approach provides complementary information and more detailed understanding of peritumoral fiber tract alterations in gliomas which are more complex as described so far. We presented a classification model for systematic assessment of these alterations that may be helpful for treatment planning and prediction of patients' prognoses.

Topics: Adult; Aged; Brain Neoplasms; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Female; Fluorine Radioisotopes; Glioma; Humans; Magnetic Resonance Imaging; Male; Medical Oncology; Middle Aged; Nervous System Diseases; Neurology; Neurons; Positron-Emission Tomography; Prognosis; Tyrosine

The aim of this prospective pilot study in patients with suspected or known brain tumour was to establish the diagnostic value of O-(2-[(18)F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) when compared to fluorine-18 fluorodeoxyglucose (FDG) PET. Twenty-five FET PET and FDG PET scans were performed on 21 consecutive patients within 24 months. Final malignant pathology included 11 glioma (eight low-grade, three high grade), two lymphoma, one olfactory ganglioneuroblastoma, one anaplastic meningioma. Benign pathology included two encephalitis and one cortical dysplasia. Definitive pathology was not available in three patients. The accuracy of PET was determined by subsequent surgical histopathology in 12 and clinical/imaging course in nine patients. Median follow-up period was 20 months. FET sensitivity was 93%, specificity 100%, accuracy 96%, positive predictive value (PPV) 100% and negative predictive value (NPV) 91%. FDG sensitivity was 27%, specificity 90%, accuracy 52%, PPV 80% and NPV 45%. FET PET is more accurate than FDG PET for detecting malignant brain lesions, especially low-grade gliomas.

Topics: Adult; Aged; Brain; Brain Neoplasms; Diagnosis, Differential; Diagnostic Errors; Female; Fluorodeoxyglucose F18; Glioma; Humans; Lymphoma; Male; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; Prospective Studies; Radioisotopes; Reproducibility of Results; Sensitivity and Specificity; Tyrosine; Young Adult

Standard magnetic resonance imaging (MRI) does not depict the true extent of tumour cell invasion in gliomas. We investigated the feasibility of advanced imaging methods, i.e. diffusion tensor imaging (DTI), fibre tracking and O-(2-[(18)F]-fluoroethyl)-L: -tyrosine ((18)F-FET) PET, for the detection of tumour invasion into white matter structures not visible in routine MRI.. DTI and fibre tracking was performed on ten patients with gliomas, WHO grades II-IV. Five patients experienced preoperative sensorimotor deficits. The ratio of fractional anisotropy (FA) between the ipsilateral and contralateral pyramidal tract was calculated. Twenty-one stereotactic biopsies from five patients were histopathologically evaluated for the absolute numbers and percentages of tumour cells. (18)F-FET PET scans were performed and the bilateral ratio [ipsilateral-to-contralateral ratio (ICR)] of (18)F-FET-uptake was calculated for both cross-sections of pyramidal tracts and biopsy sites.. The FA ratio within the pyramidal tract was lower in patients with sensorimotor deficits (0.61-1.06) compared with the FA ratio in patients without sensorimotor deficits (0.92-1.06). In patients with preoperative sensorimotor deficits, we found a significantly (p = 0.028) higher ICR of (18)F-FET uptake (1.01-1.59) than in patients without any deficits (0.96-1.08). The ICR of (18)F-FET-uptake showed a strong correlation (r = 0.696, p = 0.001) with the absolute number of tumour cells and a moderate correlation (r = 0.535, p = 0.012) with the percentage of tumour cells.. Our data show an association between preoperative sensorimotor deficits, increased (18)F-FET uptake and decreased FA ratio in the pyramidal tract. We demonstrated a correlation between tumour invasion and (18)F-FET uptake. These findings may help to distinguish between edema versus tumour-associated neurological deficits and could prevent the destruction of important structures, like the pyramidal tract, during tumour operations by allowing more precise preoperative planning.

Topics: Adult; Aged; Brain; Brain Neoplasms; Contrast Media; Diffusion Magnetic Resonance Imaging; Female; Glioma; Humans; Male; Middle Aged; Movement Disorders; Neoplasm Invasiveness; Positron-Emission Tomography; Predictive Value of Tests; Pyramidal Tracts; Radiography; Sensation Disorders; Sensitivity and Specificity; Tyrosine

Malignant gliomas are highly infiltrative tumours with a fatal prognosis. F18-fluoroethyl-tyrosine (FET)-positron emission tomography (PET) often reveals a broader extension of these tumours compared with contrast-enhanced magnetic resonance imaging (MRI). Complete resection of the contrast-enhancing lesion is aspired. Fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) improved the extent of resection. In this study, we investigated whether the FET uptake correlates with the extent of resection using 5-ALA-induced fluorescence.. Thirteen patients who underwent preoperative and postoperative MRI, FET-PET and fluorescence-guided neuronavigated resection were included in this study. The areas in which intraoperative fluorescence terminated the resection were marked. After fusion of PET and MRI, the standardized uptake value (SUV) of FET related to normal brain (SUV(R)) was measured in regions of interest corresponding to resected and remaining tissue, respectively. Receiver-operating characteristic (ROC) curve analysis determined the optimal threshold of the relative SUV anticipating 5-ALA-induced fluorescence.. During resection a vivid fluorescence was present in all patients. Histology revealed glioblastomas in 11 cases, an anaplastic astrocytoma in one case and a low-grade astrocytoma in one case. The median FET SUV(R) was higher in areas corresponding to the fluorescent tumour compared with the non-fluorescent normal brain (2.321 vs 1.142, p < 0.0001, t-test). A SUV(R) greater than 1.374 predicted the fluorescence with a sensitivity of 0.87 [95% confidence interval (CI): 0.74-0.94] and a specificity of 0.94 (CI: 0.84-0.99). The area under the ROC curve was 0.9656 (CI: 0.9364-0.9948).. FET uptake predicts the 5-ALA-induced fluorescence in glioma patients. Thus, FET-PET provides useful information for planning glioma resection.

Topics: Adult; Aged; Aminolevulinic Acid; Biomarkers, Tumor; Brain Neoplasms; Female; Fluorescence; Glioma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Monitoring, Intraoperative; Neuronavigation; Neurosurgical Procedures; Positron-Emission Tomography; Predictive Value of Tests; Preoperative Care; Tyrosine

To explore prospectively the positive predictive value of O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET)-PET in selected patients with a magnetic resonance imaging (MRI)-based suspicion of a glioma recurrence or progression. Methods Patients with a supratentorial glioma (initial World Health Organization (WHO) grade II, III or IV) were considered eligible if they had both an MRI-(new/progressive contrast-enhancing lesion) and FET-PET-based diagnosis of a recurrence/progression after various forms and combinations of irradiation and chemotherapy. Criterion for tumour recurrence/progression in FET-PET was a standardized uptake value (SUVmax)/Background (BG) ratio of >2.0 in the late uptake phase. All patients underwent multimodal (MRI, FET-PET) imaging-guided stereotactic biopsy. The positive predictive value was defined as the proportion of MRI and FET-PET findings indicating glioma recurrence/progression that also tested positive for tumour recurrence/progression after stereotactic biopsy.. Thirty-one patients with initially WHO grade II (17), WHO grade III (6), and grade IV glioma (8) were included. In 26 patients FET-PET results indicating tumour recurrence/progression were concordant with the biopsy results. In five patients histopathologic evaluation failed to reveal a "vital" tumour. FET-PET findings were also discordant with the radiographic and clinical follow-up in these five patients. The positive predictive value of FET-PET was 84%.. The positive predictive value of FET-PET using the standard ratio method is high, but not high enough to replace stereotactic biopsy in this highly selected study cohort. Whether the calculation of FET uptake in the early phase and/or the evaluation of uptake kinetics will improve the positive predictive value of FET-PET deserves prospective evaluation.

Topics: Adult; Aged; Biopsy; Brain Neoplasms; Cell Proliferation; Combined Modality Therapy; Disease Progression; Female; Glioma; Humans; Ki-67 Antigen; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; Radiopharmaceuticals; Stereotaxic Techniques; Tyrosine

Nonspecific incidental brain lesions (NILs) are being detected more frequently because of an increasing number of screening or research MRI scans of the brain, and their natural course is uncertain.. In a prospective cohort study starting in 1999, we determined the outcomes of patients with incidental, nonenhancing, supratentorial, lobar, and small-volume (<10 mL) lesions, depending on the findings of MRI and PET with the (18)F-labeled amino acid fluoroethyl-l-tyrosine ((18)F-FET). Patients with seizures, focal neurologic deficits, signs of local or systemic infection or inflammation, known brain disease, or any kind of previous cerebral treatment were excluded. Finally, 21 patients were eligible. MRI was performed in 19 of these patients because of nonspecific symptoms (such as headaches, dizziness, or sudden deafness), whereas 2 patients were healthy volunteers in MRI studies. Clinical follow-up and MRI scans were obtained at 4- to 6-mo intervals, and follow-up ranged from 3 to 8.5 y. Mean lesion-to-brain (L/B) ratios of >or=1.6 on (18)F-FET PET were rated as positive.. Four different outcome groups were identified. In group A, 5 NILs regressed or vanished completely. All of these lesions were circumscribed on MRI, and (18)F-FET uptake was negative, with an L/B ratio of 1.2+/-0.2 (mean +/- SD). In group B, 10 NILs were stable, without growth. All of these lesions were circumscribed on MRI, and (18)F-FET uptake was negative (L/B ratio: 1.0+/-0.1). In group C, 2 NILs grew slowly over years, and an astrocytoma of World Health Organization (WHO) grade II was diagnosed after resection in each case. The lesions were circumscribed on MRI, and (18)F-FET uptake was negative (L/B ratios: 0.7 and 1.0). In group D, 4 NILs showed sudden and rapid growth, with clinical deterioration, and a high-grade glioma of WHO grade III or IV was diagnosed after resection in all cases. The lesions were diffuse on MRI, and (18)F-FET uptake was significantly increased (L/B ratio: 2.0+/-0.4) (P<0.01 for group D vs. group A or group B).. For NILs, a circumscribed growth pattern on MRI and normal or low (18)F-FET uptake on PET are strong predictors for a benign course, with the eventual development of a low-grade glioma. In contrast, NILs with a diffuse growth pattern on MRI and increased (18)F-FET uptake indicate a high risk for the development of a high-grade glioma.

Topics: Adolescent; Adult; Aged; Brain; Child; Disease Progression; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Prognosis; Tyrosine

The aim of this study was to determine the spatial correlation of O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) uptake and the concentrations of choline (Cho), creatine (Cr), and total N-acetylaspartate (tNAA) determined with proton magnetic resonance spectroscopic imaging ((1)H MRSI) in cerebral gliomas for the multimodal evaluation of metabolic changes.. (18)F-FET PET and 2-dimensional (1)H MRSI were performed in 15 patients with cerebral gliomas of World Health Organization (WHO) grades II-IV. PET and (1)H MRSI datasets were coregistered by use of mutual information. On the basis of their levels of (18)F-FET uptake, 4 different areas in a tumor (maximum, strong, moderate, and low (18)F-FET uptake) were defined on PET slices as being congruent with the volume of interest in the (1)H MRSI experiment. (18)F-FET uptake in lesions was evaluated as tumor-to-brain ratios. Metabolite concentrations for Cho, Cr, and tNAA and Cho/tNAA ratios were computed for these 4 areas in the tumor and for the contralateral normal brain.. In the area with maximum (18)F-FET uptake, the concentration of tNAA (R= -0.588) and the Cho/tNAA ratio (R=0.945) correlated significantly with (18)F-FET uptake. In the areas with strong and moderate (18)F-FET uptake, only the Cho/tNAA ratios (R=0.811 and R=0.531, respectively) were significantly associated with amino acid transport. At low (18)F-FET uptake, analysis of the correlations of amino acid uptake and metabolite concentrations yielded a significant result only for the concentration of Cr (R=0.626). No correlation was found for metabolite concentrations determined with (1)H MRSI and (18)F-FET uptake in normal brain tissue. Maximum (18)F-FET uptake and the tNAA concentration were significantly different between gliomas of WHO grades II and IV, with P values of 0.032 and 0.016, respectively.. High (18)F-FET uptake, which is indicative of tumor cell infiltration, associates with neuronal cell loss (tNAA) and changes in ratios between parameters representing membrane proliferation and those of neuronal loss (Cho/tNAA ratio), which can be measured by (1)H MRSI. The significant correlation coefficients detected for Cr in regions with low (18)F-FET uptake suggests an association between the mechanism governing amino acid transport and energy metabolism in areas that are infiltrated by tumor cells to a lesser extent. These findings motivate further research directed at investigating the potential of (1)H MRSI to define tumor boundaries in a manner analogous to that of amino acid PET.

Topics: Adult; Aged; Cell Membrane; Cerebrum; Energy Metabolism; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neurons; Positron-Emission Tomography; Protons; Tyrosine

Targeting extracellular structures that are involved in angiogenic processes, such as the extra domain B of fibronectin, is a promising approach for the diagnosis of solid tumors. The aim of this study was to determine uptake of the (18)F-labeled PET tracers (18)F-fluorocholine (N,N-dimethyl-N-(18)F-fluoromethyl-2-hydroxyethylammonium), (18)F-fluoro-ethyl-l-tyrosine (FET), and (18)F-FDG in C6 gliomas of the rat and to correlate it with uptake of the anti-extra domain B antibody (131)I-SIP(L19) as a marker of neoangiogenesis.. C6 gliomas were orthotopically induced in 17 rats. Uptake of all tracers was measured using quantitative autoradiography, and uptake of (18)F-fluorocholine, (18)F-FET, and (18)F-FDG was correlated with uptake of (131)I-SIP(L19) on a pixelwise basis.. The mean (131)I-SIP(L19), (18)F-fluorocholine, (18)F-FET, and (18)F-FDG standardized uptake values in the tumor and the contralateral normal cortex (in parentheses) were 0.31 +/- 0.22 (not detectable), 2.00 +/- 0.53 (0.49 +/- 0.07), 3.67 +/- 0.36 (1.42 +/- 0.22), and 7.23 +/- 1.22 (3.64 +/- 0.51), respectively. The (131)I-SIP(L19) uptake pattern correlated best with (18)F-fluorocholine uptake (z = 0.80, averaged z-transformed Pearson correlation coefficient) and (18)F-FET uptake (z = 0.79) and least with (18)F-FDG (z = 0.37).. One day after intravenous injection, (131)I-SIP(L19) displayed a very high tumor-to-cortex ratio, which may be used in the diagnostic work-up of brain tumor patients. Of the 3 investigated (18)F tracers, (18)F-fluorocholine and (18)F-FET correlated better with the pattern of (131)I-SIP(L19) uptake than did (18)F-FDG. Whether this means that (18)F-fluorocholine and (18)F-FET are better suited than (18)F-FDG to monitor antiangiogenic therapy should be investigated in future studies.

Topics: Animals; Antibodies; Brain Neoplasms; Cell Line, Tumor; Choline; Fibronectins; Glioma; Male; Neovascularization, Pathologic; Radiopharmaceuticals; Rats; Rats, Wistar; Recombinant Fusion Proteins; Tyrosine

Many low-grade gliomas (World Health Organization grade II) respond to chemotherapy. Cerebral blood flow (CBF) and microvessel density may be critical for drug delivery. We used PET with (18)F-fluoro-ethyl-l-tyrosine (FET) to measure the spatial distribution of the amino acid carrier, which is located at the brain capillaries, and (15)O-H(2)O to measure tumor CBF.. Seventeen patients with low-grade glioma were studied. Region-of-interest (ROI) analysis was used to quantify tumor tracer uptake, which was normalized to cerebellar uptake (tumor-to-cerebellum ratio). "Active" tumor was defined as tumor having a radioactivity concentration that was at least 110% of the cerebellar activity. This threshold provided measures of active tumor volume, global and peak tumor CBF, and (18)F-FET uptake. Trace ROIs were applied to create voxelwise profiles of CBF and (18)F-FET uptake across tumor and brain. Standard MRI sequences were used for spatial correlations.. Fourteen of 17 tumors showed increased global CBF and (18)F-FET uptake. Active tumor volumes ranged between 3 and 270 cm(3) for (18)F-FET and between 1 and 41 cm(3) for CBF. Global (18)F-FET uptake in tumors corresponded to CBF increases (Spearman rank rho = 0.771, P < 0.01). The volumes of increased CBF and (18)F-FET uptake spatially coincided and were also correlated (rho = 0.944, P < 0.01). Trace ROIs showed that irrespective of increased (18)F-FET uptake at the tumor periphery, CBF increases were more confined to the tumor center. Within individual tumors, spatial heterogeneity was present. Particular tumors infiltrating the corpus callosum showed low CBF and (18)F-FET uptake in this tumor region. The patterns observed with PET were not reflected on MRI of the tumors, all of which presented as homogeneous non-gadolinium-enhancing lesions.. Low-grade gliomas are heterogeneous tumors with regard to the distribution of amino acid uptake and CBF. Both are coupled in the tumor center. At the tumor periphery, where tumor infiltration of surrounding brain occurs, CBF may be low irrespective of increased (18)F-FET uptake. An ongoing study is investigating the effect of chemotherapy on these observations.

Topics: Adult; Amino Acid Transport Systems; Brain Neoplasms; Capillaries; Cerebellum; Female; Fluorine Radioisotopes; Glioma; Humans; Male; Microcirculation; Middle Aged; Oxygen Isotopes; Oxygen Radioisotopes; Positron-Emission Tomography; Radiopharmaceuticals; Tyrosine; Water

Treatment and prognosis of gliomas depend on their histological tumour grade. The aim of the study was to evaluate the potential of [(18)F]fluoroethyltyrosine (FET) PET for non-invasive tumour grading in untreated patients.. Dynamic FET PET studies were performed in 54 patients who, based on MRI, were estimated to have low grade (LG; n = 20), intermediate (WHO II-III; n = 4) or high grade (HG; n = 30) tumours. For standard evaluation, tumour SUV(max) and the ratio to background (SUV(max)/BG) were calculated (sum image: 20-40 min). For dynamic evaluation, mean SUV values within a 90% isocontour ROI (SUV90) and the SUV90/BG ratios were determined for each time frame to evaluate the course of FET uptake. Results were correlated with histopathological findings from PET-guided stereotactic biopsies.. Histology revealed gliomas in all patients. Using the standard method a statistically significant difference (p = 0.001) was found between LG (n = 20; SUV(max)/BG: 2.16 +/- 0.98) and HG (n = 34; SUV(max)/BG: 3.29 +/- 1.06) gliomas (opt. threshold 2.58: SN71%/SP85%/area under ROC curve [AUC]:0.798), however, with a marked overlap between WHO II to IV tumours. Time activity curves showed slight increase in LG, whereas HG tumours presented with an early peak (10-20 min) followed by a decrease. Dynamic evaluation successfully separated LG from HG gliomas with higher diagnostic accuracy (SN94%/SP100%/AUC:0.967).. Based on the ratio-based method, a statistically significant difference was found between LG and HG gliomas. Due to the interindividual variability, however, no reliable individual grading was possible. In contrast, dynamic evaluation allowed LG and HG gliomas to be differentiated with high diagnostic power and, thus, should supplement the conventional method.

Topics: Adolescent; Adult; Aged; Brain Neoplasms; Female; Glioma; Humans; Image Interpretation, Computer-Assisted; Male; Metabolic Clearance Rate; Middle Aged; Neoplasm Staging; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Statistics as Topic; Tyrosine

The positron emission tomography (PET) tracers (18)F-fluoro-ethyl-L: -tyrosine (FET), (18)F-fluorocholine (N,N-dimethyl-N-[(18)F]fluoromethyl-2-hydroxyethylammonium (FCH]) and (18)F-fluoro-2-deoxyglucose (FDG) are used in the diagnosis of brain tumours. The aim of this study was threefold: (a) to assess the uptake of the different tracers in the F98 rat glioma, (b) to evaluate the impact of blood-brain barrier (BBB) disruption and microvessel density (MVD) on tracer uptake and (c) to compare the uptake in the tumours to that in the radiation injuries (induced by proton irradiation of healthy rats) of our previous study.. F98 gliomas were induced in 26 rats. The uptake of FET, FCH and FDG was measured using autoradiography and correlated with histology, disruption of the BBB and MVD.. The mean FET, FCH and FDG standardised uptake values (SUVs) in the tumour and the contralateral normal cortex (in parentheses) were 4.19+/-0.86 (1.32+/-0.26), 2.98+/-0.58 (0.51+/-0.11) and 11.02+/-3.84 (4.76+/-1.77) respectively. MVD was significantly correlated only with FCH uptake. There was a trend towards a negative correlation between the degree of BBB disruption and FCH uptake and a trend towards a positive correlation with FET uptake. The ratio of the uptake in tumours to that in the radiation injuries was 1.97 (FCH), 2.71 (FET) and 2.37 (FDG).. MVD displayed a significant effect only on FCH uptake. The degree of BBB disruption seems to affect the accumulation of FET and FCH, but not FDG. Mean tumour uptake for all tracers was significantly higher than the accumulation in radiation injuries.

Topics: Animals; Blood-Brain Barrier; Brain Injuries; Brain Neoplasms; Cell Line, Tumor; Choline; Fluorodeoxyglucose F18; Glioma; Male; Metabolic Clearance Rate; Radiation Injuries; Radionuclide Imaging; Radiopharmaceuticals; Rats; Rats, Inbred F344; Tyrosine

MRI is commonly used to determine the location and extent of cerebral gliomas. We investigated whether the diagnostic accuracy of MRI could be improved by the additional use of PET with the amino acid O-(2-[18F]fluoroethyl)-l-tyrosine (FET). In a prospective study, PET with FET and MRI was performed in 31 patients with suspected cerebral gliomas. PET and MRIs were co-registered and 52 neuronavigated tissue biopsies were taken from lesions with both abnormal MRI signal and increased FET uptake (match), as well as from areas with abnormal MR signal but normal FET uptake or vice versa (mismatch). Biopsy sites were labelled by intracerebral titanium pellets. The diagnostic performance for the identification of cellular tumour tissue was analysed for either MRI alone or MRI combined with FET PET using alternative free response receiver operating characteristic curves (ROCs). Histologically, 26 biopsy samples corresponded to cellular glioma tissue and 26 to peritumoral brain tissue. The diagnostic performance, as determined by the area under the ROC curve (Az), was Az = 0.80 for MRI alone and Az = 0.98 for the combined MRI and FET PET approach (P < 0.001). MRI yielded a sensitivity of 96% for the detection of tumour tissue but a specificity of only 53%, and combined use of MRI and FET PET yielded a sensitivity of 93% and a specificity of 94%. Combined use of MRI and FET PET in patients with cerebral gliomas significantly improves the identification of cellular glioma tissue and allows definite histological tumour diagnosis. Thus, our findings may have considerable impact on target selection for diagnostic biopsies as well as therapy planning.

Topics: Adolescent; Adult; Aged; Biopsy; Brain Neoplasms; Child; Child, Preschool; Female; Fluorine Radioisotopes; Glioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Prospective Studies; Sensitivity and Specificity; Tyrosine

The purpose of this study was to determine the predictive value of [18F]fluoroethyl-L-tyrosine (FET)-positron emission tomography (PET) and magnetic resonance (MR) spectroscopy for tumor diagnosis in patients with suspected gliomas.. Both FET-PET and MR spectroscopy analyses were performed in 50 consecutive patients with newly diagnosed intracerebral lesions supposed to be diffuse gliomas on contrast-enhanced MR imaging. Lesion/brain ratios of FET uptake greater than 1.6 were considered positive, that is, indicative of tumor. Results of MR spectroscopy were considered positive when N-acetylaspartate (NAA) was decreased in conjunction with an absolute increase of choline (Cho) and an NAA/Cho ratio of 0.7 or less. An FET lesion/brain ratio, an NAA/Cho ratio, and signal abnormalities on MR images were compared with histological findings in neuronavigated biopsy specimens. The FET lesion/brain ratio and the NAA/Cho ratio were identified as significant independent predictors for the histological identification of tumor tissue. The accuracy in distinguishing neoplastic from nonneoplastic tissue could be increased from 68% with the use of MR imaging alone to 97% with MR imaging in conjunction with FET-PET and MR spectroscopy. Sensitivity and specificity for tumor detection were 100 and 81% for MR spectroscopy and 88 and 88% for FET-PET, respectively. Results of histological studies did not reveal tumor tissue in any of the lesions that were negative on FET-PET and MR spectroscopy. In contrast, a tumor diagnosis was made in 97% of the lesions that were positive with both methods.. In patients with intracerebral lesions supposed to be diffuse gliomas on MR imaging, FET-PET and MR spectroscopy analyses markedly improved the diagnostic efficacy of targeted biopsies.

Topics: Adolescent; Adult; Aged; Aspartic Acid; Biopsy; Brain; Brain Neoplasms; Child; Child, Preschool; Choline; Energy Metabolism; Female; Fluorine Radioisotopes; Glioma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neuronavigation; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Sensitivity and Specificity; Tyrosine

2-Deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) has been extensively used as positron emission tomography (PET) tracer in clinical tumor imaging. This study compared the pharmacokinetics of two (18)F-labeled amino acid derivatives, O-2-[(18)F]fluoroethyl-l-tyrosine (l-[(18)F]FET) and 4-borono-2-[(18)F]fluoro-l-phenylalanine-fructose (l-[(18)F]FBPA-Fr), to that of [(18)F]FDG in an animal brain tumor model.. A self-modified automated PET tracer synthesizer was used to produce no-carrier-added (nca) l-[(18)F]FET. The cellular uptake, biodistribution, autoradiography and microPET imaging of l-[(18)F]FET, l-[(18)F]FBPA-Fr and [(18)F]FDG were performed with F98 glioma cell culture and F98 glioma-bearing Fischer344 rats.. The radiochemical purity of l-[(18)F]FET was >98% and the radiochemical yield was 50% in average of 16 runs. The uptake of l-[(18)F]FET and l-[(18)F]FBPA-Fr in the F98 glioma cells increased rapidly for the first 5 min and reached a steady-state level after 10 min of incubation, whereas the cellular uptake of [(18)F]FDG kept increasing during the study period. The biodistribution of l-[(18)F]FET, l-[(18)F]FBPA-Fr and [(18)F]FDG in the brain tumors was 1.26+/-0.22, 0.86+/-0.08 and 2.77+/-0.44 %ID/g at 60 min postinjection, respectively, while the tumor-to-normal brain ratios of l-[(18)F]FET (3.15) and l-[(18)F]FBPA-Fr (3.44) were higher than that of [(18)F]FDG (1.44). Both microPET images and autoradiograms of l-[(18)F]FET and l-[(18)F]FBPA-Fr exhibited remarkable uptake with high contrast in the brain tumor, whereas [(18)F]FDG showed high uptake in the normal brain and gave blurred brain tumor images.. Both l-[(18)F]FET and l-[(18)F]FBPA-Fr are superior to [(18)F]FDG for the brain tumor imaging as shown in this study with microPET.

Topics: Animals; Boron Compounds; Brain; Brain Neoplasms; Cell Line, Tumor; Disease Models, Animal; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Glioma; Glycopeptides; Metabolic Clearance Rate; Molecular Probe Techniques; Organ Specificity; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Tissue Distribution; Tyrosine

Topics: Animals; Autoradiography; Brain; Brain Chemistry; Brain Diseases; Brain Neoplasms; Glioma; Humans; Magnetic Resonance Imaging; Positron-Emission Tomography; Proline; Rats; Tyrosine

The transport mechanisms of O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) and 2-[(18)F]fluoro-L-tyrosine (FTyr) were compared to those of [(3)H]-Methyl-L-methionine (MET) in F98 rat glioma cells in vitro and by tumor imaging by ex vivo dual tracer autoradiography in F98 rat gliomas. Both, FET and FTyr exhibited similar transport characteristics in F98 glioma cells compared to MET, i.e. mainly a sodium dependent transport similar to system B(0,+) and sodium independent transport via system L. Radioactivity of FET in the acid precipitable fraction was <1% after 120 min incubation time while FTyr and MET exhibited a 15-18% incorporation into proteins. Comparison of FET and FTyr with MET uptake in F98 rat gliomas demonstrated a significant correlation of tumor to brain ratios and a similar intratumoral tracer distribution pattern.

Topics: Animals; Autoradiography; Brain; Brain Neoplasms; Cell Line, Tumor; Glioma; Male; Methionine; Radionuclide Imaging; Radiopharmaceuticals; Rats; Rats, Inbred F344; Tissue Distribution; Tissue Transplantation; Tyrosine