carbon-11-methionine and Glioma

To perform a meta-analysis evaluating the diagnostic accuracy of . A systematic database search was performed by a librarian in relevant databases with the latest search on 07 November 2016. Hits were assessed for inclusion independently by two authors. Individual patient data on relative MET uptake was extracted on patients examined pre-operatively with MET PET and subsequent neuropathological diagnosis of astrocytoma or oligodendroglioma. Individual patient data were analysed for diagnostic accuracy using a bivariate diagnostic random-effects meta-analysis model with restricted maximum likelihood estimation method. Bivariate meta-regression and subgroup analyses assessed study heterogeneity and validity. This study is registered with PROSPERO, number CRD42016050747.. Out of 1828 hits, 13 studies comprising of 241 individuals were included in the quantitative and qualitative analysis. MET PET had an area under the bivariate summary receiver operating characteristics curve of 0.78 to discriminate between LGG and HGG and a summary sensitivity of 0.80 with 95% confidence interval (CI) (0.66-0.88) and a summary false positive rate of 0.28, 95% CI (0.19-0.38). Heterogeneity was described by; bias in patient inclusion, study quality, and ratio method. Optimal cutoff for relative MET uptake was 2.21.. MET PET had a moderately high diagnostic accuracy for the discrimination between primary LGG and HGG. Advances in knowledge: MET PET can be used as a clinical tool for the non-invasive discrimination between LGG and HGG with a moderately high accuracy at cut-off 2.21.

Topics: Central Nervous System Neoplasms; Glioma; Humans; Likelihood Functions; Methionine; Neoplasm Grading; Positron-Emission Tomography; Radiopharmaceuticals; ROC Curve; Sensitivity and Specificity

This study aimed to compare the diagnostic value of ¹¹C-methionine (¹¹C-MET) PET and dynamic susceptibility contrast-enhanced (DSCE) MRI in detecting glioma recurrence by meta-analysis.. Databases such as PubMed (MEDLINE included), EMBASE, Science Direct, Springerlink, EBSCO, and Cochrane Database of Systematic Review were searched for relevant original articles on the detection of recurrent glioma using DSCE MRI or ¹¹C-MET PET with or without computed tomography. No restriction was imposed over the types and grades of glioma. The included studies were assessed for methodological quality. Results from histopathological analysis and/or close clinical and/or radiological follow-up for at least 3 months were used as the reference standard. The data were extracted by two reviewers independently to analyze the sensitivity, specificity, summary receiver-operating characteristic curve, area under the curve, and heterogeneity.. The present study analyzed a total of 17 selected articles including different types and grades of glioma and showed that ¹¹C-MET PET and DSCE MRI had comparable sensitivity (0.870 and 0.884, respectively), specificity (0.813 and 0.853, respectively), positive likelihood ratio (4.355 and 5.806, respectively), negative likelihood ratio (0.192 and 0.134, respectively), and diagnostic odds ratio (21.857 and 41.918, respectively) without statistically significant differences, except for the fact that DSCE MRI displayed higher area under the curve and Q* index compared with ¹¹C-MET PET (P<0.05).. Both ¹¹C-MET PET and DSCE MRI are accurate tools for detecting glioma recurrence. Although DSCE MRI seems to be superior to ¹¹C-MET PET, the latter can also be used to assess glioma recurrence when the former is not available.

Topics: Contrast Media; Glioma; Humans; Magnetic Resonance Imaging; Methionine; Multimodal Imaging; Positron-Emission Tomography; Recurrence

(11)C-methionine (MET) is the most popular amino acid tracer used in PET imaging of brain tumours. Because of its characteristics, MET PET provides a high detection rate of brain tumours and good lesion delineation. This review focuses on the role of MET PET in imaging cerebral gliomas. The Introduction provides a clinical overview of what is important in primary brain tumours, recurrent brain tumours and brain metastases. The indications for radiotherapy and the results and problems arising after chemoradiotherapy in relation to imaging (pseudoprogression or radionecrosis) are discussed. The working mechanism, scan interpretation and quantification possibilities of MET PET are then explained. A literature overview is given of the role of MET PET in primary gliomas (diagnostic accuracy, grading, prognosis, assessment of tumour extent, biopsy and radiotherapy planning), in brain metastases, and in the differentiation between tumour recurrence and radiation necrosis. Finally, MET PET is compared to other nuclear imaging possibilities in brain tumour imaging.

Topics: Brain Neoplasms; Glioma; Humans; Methionine; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals

Over the last two decades the large volume of research involving various brain tracers has shed invaluable light on the pathophysiology of cerebral neoplasms. Yet the question remains as to how best to incorporate this newly acquired insight into the clinical context. Thallium is the most studied radiotracer with the longest track record. Many, but not all studies, show a relationship between (201)Tl uptake and tumor grade. Due to the overlap between tumor uptake and histologic grades, (201)Tl cannot be used as the sole noninvasive diagnostic or prognostic tool in brain tumor patients. However, it may help differentiating a high-grade tumor recurrence from radiation necrosis. MIBI is theoretically a better imaging agent than (201)Tl but it has not convincingly been shown to differentiate tumors according to grade. MDR-1 gene expression as demonstrated by MIBI does not correlate with chemoresistance in high grade gliomas. Currently, MIBI's clinical role in brain tumor imaging has yet to be defined. IMT, a radio-labeled amino acid analog, may be useful for identifying postoperative tumor recurrence and, in this application, appears to be a cheaper, more widely available tool than positron emission tomography (PET). However, its ability to accurately identify tumor grade is limited. 18 F-2-Fluoro-2-deoxy-d-glucose (FDG) PET predicts tumor grade, and the metabolic activity of brain tumors has a prognostic significance. Whether FDG uptake has an independent prognostic value above that of histology remains debated. FDG-PET is effective in differentiating recurrent tumor from radiation necrosis for high-grade tumors, but has limited value in defining the extent of tumor involvement and recurrence of low-grade lesions. Amino-acid tracers, such as MET, perform better for this purpose and thus play a complementary role to FDG. Given the poor prognosis of patients with gliomas, particularly with high-grade lesions, the overall clinical utility of single photon emission computed tomography (SPECT) and PET in characterizing recurrent lesions remains dependent on the availability of effective treatments. These tools are thus mostly suited to the evaluation of treatment response in experimental protocols designed to improve the patients' outcome.

Topics: Brain; Brain Neoplasms; Choline; Fluorodeoxyglucose F18; Glioma; Methionine; Methyltyrosines; Predictive Value of Tests; Radiopharmaceuticals; Technetium Tc 99m Sestamibi; Thallium; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

The purpose of this study was to monitor the metabolic effects of temozolomide (TMZ) chemotherapy in malignant gliomas by means of repeated positron emission tomography (PET) with [(11)C]methionine (MET).. Fifteen patients with histologically proven malignant glioma were treated by TMZ chemotherapy. MET-PET studies were performed before and after the third cycle of TMZ chemotherapy in all patients, and in 12 patients also after the sixth cycle. Gadolinium-enhanced MRI studies were performed in 12 patients before the first and after the sixth cycle. Clinical status was assessed by the modified Rankin scale. Long-term outcome was assessed by calculating the time to progression (TTP) in months.. Decline in MET uptake during therapy corresponded to a stable clinical status. The median TTP was significantly longer in patients with decline in MET uptake than in those with increasing MET uptake (23 vs 3.5 months; p=0.01, log rank test). There was no significant correlation between change in MET uptake and change in contrast enhancement during treatment for all patients.. The present data demonstrate that clinical stability, which is often achieved under TMZ chemotherapy of malignant glioma, corresponds to a decline in or stability of tumour amino acid metabolism. Tumour responses can already be demonstrated with MET-PET after three cycles of chemotherapy, and absence of progression at that time indicates a high probability of further stability during the next three cycles. A reduction in MET uptake during TMZ treatment predicts a favourable clinical outcome. Molecular imaging of amino acid uptake by MET-PET offers a new method of measurement of the biological activity of recurrent glioma.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Dacarbazine; Female; Glioma; Humans; Male; Methionine; Middle Aged; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Temozolomide; Treatment Outcome

The uptake of L-methyl-11C-methionine (MET) by gliomas is greater than that by intact tissue, making methionine very useful for evaluation of tumor extent. If the degree of malignancy of brain tumors can be evaluated by MET-PET, the usefulness of MET-PET as a means of diagnosing brain tumors will increase.. We performed this study on 67 glioma patients between 3 and 69 years of age (36 males and 31 females). Tumors included diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, ependymoma, oligodendroglioma, medulloblastoma, dysembryoplastic neuroepithelial tumor, choroid plexus papilloma, central neurocytoma, optic glioma, gliomatosis cerebri, pleomorphic xanthoastrocytoma, and ganglioglioma. Tumor activity and degree of malignancy were evaluated using Ki-67LI (LI: labeling index) and Kaplan-Meier survival curves. The correlations between methionine uptake and tumor proliferation (tumor versus contralateral gray matter ratio (T/N) and Ki-67LI) were determined for the group of all subjects. The existence of significant correlations between T/N and Ki-67LI and between SUV and Ki-67LI was determined for astrocytic tumors. Receiver operating characteristics (ROC) analysis of T/N and standardized uptake value (SUV) was performed for the group of astrocytic tumors. We also determined the ROC cut-off levels to ensure high accuracy of the analysis.. For the 67 cases of glioma, the degree of accumulation was variable. Ki-67LI differed significantly between the high-grade group and low-grade group at T/N levels between 1.5 and 1.8 on analysis using tumor proliferative potential (p = 0.019-0.031). The prognosis differed significantly between the high-grade and low-grade groups when T/N was in the range of 1.6-1.8 (p = 0.028-0.032). The accuracy thus calculated was highest (85.7%) when T/N was 1.5 as determined by ROC analysis.. When analysis was confined to cases of astrocytic tumor, a correlation was noted between methionine accumulation and Ki-67LI. For the astrocytic tumors, T/N ratio seemed to be more useful as a diagnostic indicator than SUV. The cut-off level of T/N ratio for distinction between high-grade and low-grade astrocytoma appears to lie between 1.5 and 1.6.

Topics: Adolescent; Adult; Aged; Brain Neoplasms; Child; Child, Preschool; Female; Glioma; Humans; Image Interpretation, Computer-Assisted; Male; Methionine; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; ROC Curve; Sensitivity and Specificity; Statistics as Topic; Tissue Distribution

We compared the contributions of the labeled tracers (11)C-methionine (Met) and (18)F-FDG for PET-guided stereotactic biopsy of brain gliomas.. In 32 patients with glioma, stereotactic Met PET and (18)F-FDG PET were integrated in the planning of stereotactic brain biopsy. PET images were analyzed to determine which tracer offered the best information for target definition. The stereotactic coregistration of PET images allowed accurate comparison of the level, distribution, and extent of uptake for both tracers according to tumor location and grade.. A histologic diagnosis was obtained for all patients. All gliomas had an area of abnormal Met uptake, and 27 showed abnormal (18)F-FDG uptake. (18)F-FDG was used for target selection when its uptake was higher in tumor than in gray matter (14 gliomas). Seven were in the basal ganglia or brain stem. Met was used for target selection when there was no (18)F-FDG uptake or when (18)F-FDG uptake was equivalent to that in the gray matter (18 gliomas). Thirteen were in the cortex. Sixty-one of the 70 stereotactic trajectories obtained from the 32 patients were based on PET-defined targets and had an area of abnormal Met uptake. These 61 Met-positive trajectories always yielded a diagnosis of tumor. All nondiagnostic trajectories (n = 9) were obtained in areas with no increased uptake of Met. In all patients with increased uptake of both tracers, the focus of highest Met uptake corresponded to the focus of highest (18)F-FDG uptake. However, the extent of uptake of both tracers was variable.. Distributions of highest Met and (18)F-FDG uptake are similar in brain gliomas. Because Met provides a more sensitive signal, it is the molecule of choice for single-tracer PET-guided neurosurgical procedures in gliomas.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biopsy; Brain Neoplasms; Child; Child, Preschool; Female; Fluorodeoxyglucose F18; Glioma; Humans; Male; Methionine; Middle Aged; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Stereotaxic Techniques; Surgery, Computer-Assisted; Tomography, Emission-Computed

Following stereotactic radiosurgery (SRS), we examined how to differentiate radiation necrosis from recurrent malignant glioma using positron emission tomography (PET) with 11C-methionine (Met).. Met-PET scans were obtained from 11 adult cases of recurrent malignant glioma or radiation injury, suspected on the basis of magnetic resonance images (MRI). Patients had previously been treated with SRS after primary treatment. PET images were obtained as a static scan of 10 minutes performed 20 minutes after injection of Met. We defined two visual grades (e.g., positive or negative Met accumulation). On Met-PET scans, the portion of the tumor with the highest accumulation was selected as the region of interest (ROI), tumor-versus-normal ratio (TN) was defined as the ratio of average radioisotope counts per pixel in the tumor (T), divided by average counts per pixel in normal gray matter (N). The standardized uptake value (SUV) was calculated over the same tumor ROI. Met-PET scan accuracy was evaluated by correlating findings with subsequent histological analysis (8 cases) or, in cases without surgery or biopsy, by the subsequent clinical course and MR findings (3 cases).. Histological examinations in 8 cases showed viable glioma cells with necrosis in 6 cases, and necrosis without viable tumor cells in 2 cases. Three other cases were considered to have radiation necrosis because they exhibited stable neurological symptoms with no sign of massive enlargement of the lesion on follow-up MR after 5 months. Mean TN was 1.31 in the radiation necrosis group (5 cases) and 1.87 in the tumor recurrence group (6 cases). Mean SUV was 1.81 in the necrosis group and 2.44 in the recurrence group. There were no statistically significant differences between the recurrence and necrosis groups in TN or SUV. Furthermore, we made a 2 x 2 factorial cross table (accumulation or no accumulation, recurrence or necrosis). From this result, the Met-PET sensitivity, specificity, and accuracy in detecting tumor recurrence were determined to be 100%, 60%, and 82% respectively. In a false positive-case, glial fibrillary acidic protein (GFAP) immunostaining showed a positive finding.. There were no significant differences between recurrent malignant glioma and radiation necrosis following SRS in Met-PET. However, this study shows Met-PET has a sensitivity and accuracy for differentiating between recurrent glioma and necrosis, and presents important information for developing treatment strategies against post radiation reactions.

Topics: Adult; Brain; Brain Neoplasms; Diagnosis, Differential; Female; Glioma; Humans; Male; Methionine; Middle Aged; Necrosis; Neoplasm Recurrence, Local; Positron-Emission Tomography; Radiation Injuries; Radiopharmaceuticals; Radiosurgery; Reproducibility of Results; Sensitivity and Specificity

Dysembryoplastic neuroepithelial tumors (DNETs) are slow-growing epilepsy-associated tumors. Low or normal 11C-methionine (MET) PET uptake helps to differentiate DNETs from other low-grade gliomas. However, diverse MET-PET uptake in DNETs has been observed. The aim of this study is to measure the clinical significance and prognostic value of MET-PET in DNET management.. Retrospective review of 26 DNET patients was done. Clinical characteristics, radiologic findings, and visual and quantitative MET-PET results were analyzed. PET uptake was calculated as the tumor-to-homotopic mirror ratio (TNRm) and tumor-to-contralateral cortex ratio (TNRc). The clinical activity of the tumors at the time of PET was classified into active and quiescent groups. The surgical outcome was defined as a composite of 2 different aspects: tumor progression and/or clinical events such as seizure recurrence or tumor bleeding.. Twenty-seven MET-PET examinations (20 initial MET-PET and 7 MET-PET during follow-up) were included. Clinically active tumors at the time of PET presented significantly higher values of TNRm and TNRc than quiescent tumors. High MET-PET uptake by visual grading, TNRm ≥ 1.90, and TNRc ≥ 1.85 exhibited poor prognosis for event-free survival.. MET-PET uptake correlates well with the clinical behavior of DNETs at the time of PET examination. Moreover, High MET-PET uptake is closely related to seizure recurrence if tumors are not entirely resected. Efforts to achieve gross total resection should be made for DNETs with high MET-PET uptake.

Topics: Brain Neoplasms; Carbon Radioisotopes; Child; Glioma; Humans; Methionine; Positron-Emission Tomography; Seizures

The aim is to explore the concept of photopenic defects in newly diagnosed glioma patients with the 2 widely used C-MET and F-FDOPA PET amino acid tracers. Thirty-two C-MET and 26 F-FDOPA PET scans with amino acid PET-negative gliomas were selected in this European multicentric study. Of these gliomas, 16 C-MET and 10 F-FDOPA PET scans with photopenic defects were identified, exhibiting lower mean tumor-to-background ratio as compared with isometabolic gliomas (P < 0.001). Gliomas with photopenic defects had no different progression-free survival than isometabolic gliomas in the whole population (P = 0.40), but shorter progression-free survival in the subgroup of World Health Organization grade II IDH-mutant astrocytomas (35 vs 68 months; P = 0.047).

Topics: Adult; Aged; Brain Neoplasms; Dihydroxyphenylalanine; Female; Glioma; Humans; Male; Methionine; Middle Aged; Positron-Emission Tomography; Progression-Free Survival

The relationship between uptake of amino acid tracer with positron emission tomography (PET) and glioma subtypes/gene status is still unclear.. The participants were 68 patients with newly diagnosed and untreated glioma who underwent surgical excision and preoperative [. The mean lesion/contralateral normal brain tissue (L/N) ratio of diffuse astrocytomas was significantly lower than that of anaplastic astrocytomas (P = 0.00155), glioblastoma (P < 0.001), and oligodendrogliomas (P = 0.0157). The mean L/N ratio of IDH mutant gliomas was significantly lower than that of IDH wild-type gliomas (median 1.75 vs. 2.61; P = 0.00162). A mean L/N ratio of 2.05 provided the best sensitivity and specificity for distinguishing between IDH mutant and IDH wild-type gliomas (69.2% and 76.2%, respectively). The mean L/N ratio of TERT promoter mutant gliomas was significantly higher than that of TERT promoter wild-type gliomas (P = 0.0147). Multiple regression analysis showed that pathologic diagnosis was the only influential factor on L/N ratio.. Distinguishing glioma subtypes based on the revised 2016 World Health Organization classification of the central nervous system tumors on the basis of [

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Astrocytoma; Brain Neoplasms; Child; DNA, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Glioma; Humans; Isocitrate Dehydrogenase; Male; Methionine; Middle Aged; Mutation; Neurosurgical Procedures; Oligodendroglioma; Positron-Emission Tomography; Promoter Regions, Genetic; Radiopharmaceuticals; Retrospective Studies; Sensitivity and Specificity; Telomerase; Young Adult

A 44-year-old man after combined left temporal low-grade glioma treatment presented with daily multiple series of seizures. MRI demonstrated diffuse cortical swelling in the left frontal lobe with intensive gyral enhancement. PET with [11C]methionine (PET-MET) revealed increased radiotracer uptake strictly confined to the cortical ribbon of the left cerebral hemisphere, which persisted for 3 months. Tumor recurrence was suggested, and biopsy was performed. No evidence of recurrent tumor was found. During a 2-year follow-up, a diffuse gyral enhancement in the left hemisphere has persisted on MRI; PET has shown high [11C]methionine uptake in the left frontal and parietal cortex with gradual positive dynamics.

Topics: Adult; Biological Transport; Biopsy; Brain Neoplasms; Combined Modality Therapy; Glioma; Humans; Magnetic Resonance Imaging; Male; Methionine; Positron Emission Tomography Computed Tomography; Recurrence

In the present case, we report the first experience of a patient with high-grade glioma who underwent dual F-FAZA PET/CT imaging for intratumoral hypoxia assessment, before treatment, and for therapy monitoring in the suspicious of recurrence, as part of a clinical research protocol. In addition, despite the diagnosis of glioblastoma, the patient at 3 years from diagnosis was alive and underwent C-methionine simultaneous PET/MRI for disease monitoring after treatment, showing stability of disease. The multitracer capability of PET in assessing different and complementary metabolic features along with the use of a last-generation scanner as PET/MRI in brain oncology are here enlighten.

Topics: Adult; Amino Acids; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Methionine; Middle Aged; Neoplasm Grading; Nitroimidazoles; Positron Emission Tomography Computed Tomography; Tumor Hypoxia

To compare 11C-methionine (11C-METH) PET with diffusion-weighted MRI (DWI-MRI) diagnostic accuracy and prognostic value in patients with glioma candidate to neurosurgery.. We collected and analyzed data from 124 consecutive patients (n = 124) investigated during preoperative work-up. Both visual and semiquantitative parameters were utilized for image analysis. The reference standard was based on histopathology. The median follow-up was 14.3 months.. Overall, 47 high-grade gliomas (HGG) and 77 low-grade gliomas (LGG) were diagnosed. On visual assessment, sensitivity and specificity for differentiating HGG from LGG were 80.8 and 59.7% for DWI-MRI, versus 95.7 and 41.5% for 11C-METH PET, respectively. On semiquantitative analysis, the sensitivity, specificity, and area under the curve were 78.7, 71.4, and 80.4% for SUVmax, 78.7, 70.1, and 81.1% for SUVratio, and 74.5, 61, and 76.7% for MTB (metabolic tumor burden), respectively. In patients with negative DWI-MRI and IDH-wild type, SUVmax and SUVratio were higher compared to IDH-mutated (P = 0.025 and P = 0.01, respectively). In LGG, patients with 1p/19q codeletion showed higher SUVmax (P = 0.044). In all patients with negative DWI-MRI, median PFS was longer for SUVmax <3.9 (median not reached vs 34.2 months, P = 0.004), SUVratio <2.3 (median not reached vs 21.5 months, P < 0.001), and MTB <3.1 (median not reached vs 45.7 months, P = 0.05). In LGG patients with negative DWI-MRI, only SUVratio <2.3 and MTB <3.1 were associated with longer PFS (P = 0.016 and P = 0.024, respectively).. C-METH PET was found highly sensitive for glioma differentiation and molecular characterization. In DWI-negative patients, PET parameters correlated with molecular profile were associated with clinical outcome.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Brain Neoplasms; Diffusion Magnetic Resonance Imaging; Female; Glioma; Humans; Male; Methionine; Middle Aged; Prognosis; Young Adult

Positron emission tomography (PET) is a valuable tool for the characterization of brain tumors in vivo. However, few studies have investigated the correlation between carbon-11-methionine (11C-METH) PET metrics and the clinical, radiological, histological, and molecular features of patients affected by lower grade gliomas (LGGs). The present observational study evaluated the relationships between 11C-METH PET metrics and structural magnetic resonance imaging (MRI) findings with the histomolecular biomarkers in patients with LGGs who were candidates for surgery.. We enrolled 96 patients with pathologically proven LGG (51 men, 45 women; age 44.1 ± 13.7 years; 45 with grade II, 51 with grade III), who had been referred from March 2012 to January 2015 for tumor resection and had undergone preoperative 11C-METH PET. The semiquantitative metrics for 11C-METH PET included maximum standardized uptake value (SUVmax), SUV ratio to normal brain, and metabolic tumor burden (MTB). The PET semiquantitative metrics were analyzed and compared with the MRI features, histological diagnosis, isocitrate dehydrogenase-1/2 status, and 1p/19q codeletion.. The 11C-METH PET metrics correlated significantly with histological grade and the molecular profile. Semiquantitative PET metrics can improve the preoperative evaluation of LGGs and thus support clinical decision-making.

Topics: Adult; Biomarkers; Brain; Brain Neoplasms; Female; Glioma; Humans; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Male; Methionine; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity

To evaluate whether the combination of magnetic resonance spectroscopy (MRS) and ¹¹C-methionine positron emission tomography (¹¹C-MET PET) could increase accurate diagnostic sensitivity for non-enhancing supratentorial gliomas.. Between February 2012 and December 2017, 109 patients with non-enhanced supratentorial lesions on contrast-enhanced MRI were enrolled. Each patient underwent MRS and ¹¹C-MET PET before treatment. A lesion was considered to be a glioma when either the MRS or ¹¹C-MET PET results reached the diagnostic threshold. The radiological diagnosis was compared with the pathological diagnosis or medical diagnostic criteria.. The sensitivity and specificity were 60.0% and 50.0% for MRS and 75.8% and 50.0% for ¹¹C-MET PET, respectively. Upon combining the two modalities, the sensitivity and specificity of the imaging-based diagnosis prior to surgery reached 89.5% and 42.9%, respectively. Statistically significant differences in the sensitivities were observed between the combined and individual approaches (MRS alone, 89.5% vs. 60.0%,. The combination of MRS and ¹¹C-MET PET findings significantly increases accurate diagnostic sensitivity for non-enhancing supratentorial gliomas without significantly lowering the specificity. This finding suggests the potential of the combined MRS and ¹¹C-MET PET approach in clinical applications.

Topics: Adult; Aged; Brain Neoplasms; Carbon Radioisotopes; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Methionine; Middle Aged; Positron-Emission Tomography; Sensitivity and Specificity

We evaluate the O6-methylguanylmethyltransferase (MGMT) methylation status noninvasively by analyzing radiomics features of C-methionine (MET) PET images, which may reflect the detailed biological properties of gliomas.. Fifty-seven patients with histopathologically confirmed gliomas, who were initially examined with C-MET PET/MR were retrospectively enrolled. Quantitative uptake of MET was assessed using conventional, histogram and texture features. These features were compared between the two groups classified by MGMT promoter methylation status.. The histogram features (Skewness and Kurtosis) of the MGMT methylated group were significantly higher than those of the MGMT unmethylated group (Skewness: 0.90 ± 0.71 vs. 0.49 ± 0.45; P = 0.01) (Kurtosis: 1.36 ± 2.30 vs. 0.08 ± 0.65; P = 0.003), but there were no significant differences in Skewness or Kurtosis between the groups in glioma-grade-matched subgroup analysis. Moreover, there was no significant difference in other features between the methylated group and unmethylated group.. The histogram features (Skewness and Kurtosis) of MET PET/MRI may be two key indicators to detect MGMT methylation status in gliomas and valuable predictors for the clinical responses of patients scheduled to receive temozolomide chemotherapeutics.

Topics: Adult; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Methionine; Multimodal Imaging; Positron-Emission Tomography; Promoter Regions, Genetic; Retrospective Studies; Tumor Suppressor Proteins

Few data exist regarding the prognostic value of L-[S-methyl-11C]methionine (MET) PET for treatment-naïve gliomas.. A total of 160 glioma patients (89 men, 71 women; mean age: 45, range 18-84 y) underwent a MET PET prior to any therapy. The PET scans were evaluated visually and semiquantitatively by tumor-to-background (T/N) ratio thresholds chosen by analysis of receiver operating characteristics. Additionally, isocitrate dehydrogenase 1-R132H (IDH1-R132H) immunohistochemistry was performed. Survival analysis was done using Kaplan-Meier estimates and the Cox proportional hazards model.. Significantly shorter mean survival times (7.2 vs 8.6 y; P = 0.024) were seen in patients with amino acid avid gliomas (n = 137) compared with visually negative tumors (n = 33) in MET PET. T/N ratio thresholds of 2.1 and 3.5 were significantly associated with survival (10.3 vs 7 vs 4.3 y; P < 0.001). Mean survival differed significantly using the median T/N ratio of 2.4 as cutoff, independent of histopathology (P < 0.01; mean survival: 10.2 ± 0.8 y vs 5.5 ± 0.6 y). In the subgroup of 142 glioma patients characterized by IDH1-R132H status, METT/N ratio demonstrated a significant prognostic impact in IDH1-R132H wildtype astrocytomas and glioblastoma (P = 0.001). Additionally, multivariate testing revealed semiquantitative MET PET as an independent prognostic parameter for treatment-naïve glioma patients without (P = 0.031) and with IDH1-R132H characterization of gliomas (P = 0.024; odds ratio 1.57).. This retrospective analysis demonstrates the value of MET PET as a prognostic parameter on survival in treatment-naïve glioma patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brain Neoplasms; Female; Follow-Up Studies; Glioma; Humans; Male; Methionine; Middle Aged; Positron-Emission Tomography; Prognosis; Retrospective Studies; Survival Rate; Young Adult

Gliomas are the most common type of tumor in the brain. Although the definite diagnosis is routinely made ex vivo by histopathologic and molecular examination, diagnostic work-up of patients with suspected glioma is mainly done using MRI. Nevertheless, l-

Topics: Brain Neoplasms; Female; Glioma; Humans; Image Processing, Computer-Assisted; Male; Methionine; Middle Aged; Positron-Emission Tomography; Prognosis; Retrospective Studies; Supervised Machine Learning; Survival Analysis

To compare the diagnostic performance of amide proton transfer (APT) imaging and 11-C methionine positron emission tomography (MET-PET) for in vivo molecular imaging of protein metabolism in post-treatment gliomas.. This study included 43 patients (12 low and 31 high grade) with post-treatment gliomas who underwent both APT and MET-PET imaging within 3 weeks. APT-weighted voxel values and semi-quantitative tumour-to-normal ratios (TNR) were obtained from tumour portions. The voxel-wise relationships between TNR and APT were assessed. The diagnostic performance for recurrence of high-grade gliomas was calculated, using the area under the receiver operating characteristic curve (AUC) with maximum (TNR. A moderate positive correlation between TNR and APT was found in low-grade recurrences (r = 0.47, p < 0.001), but not in high-grade ones (r = -0.24, p < 0.001). For distinguishing recurrence in post-treatment high-grade gliomas, APT. In post-treatment high-grade gliomas, APT provides different regional information to MET-PET and provides higher diagnostic performance. This difference needs to be considered when using APT or MET-PET as a surrogate marker for tumour protein metabolism.. • APT and TNR values in low-grade recurrence showed a moderate voxel-wise correlation. • APT and TNR demonstrated regional differences in post-treatment high-grade gliomas. • APT90 showed better diagnostic performance than TNR90 in high-grade recurrence.

Topics: Adult; Aged; Amides; Biomarkers, Tumor; Brain Neoplasms; Female; Glioma; Humans; Male; Methionine; Middle Aged; Neoplasm Recurrence, Local; Positron-Emission Tomography; Protons; ROC Curve

Data sets were obtained from 32 patients with newly diagnosed glioma and 13 patients with recurrent brain tumour. Our methods were as follows: (1) FDG-PET and MET-PET images were co-registered. (2) The areas where the FDG uptake was higher than a set threshold were selected. (3) For the corresponding areas of MET-PET images, mode and mean voxel values were calculated as tentative MET N-values. (4) Applying the same coordinates to FDG-PET, the voxel values were averaged and used as tentative FDG N-values. (5) The threshold of FDG-PET and whether to use the mode or the mean voxel values were computationally optimized using learning data sets. (6) Applying the optimal threshold and either the mode or mean, N-values of FDG and MET were finally determined.. N-values determined by our automated method showed excellent agreement with those determined by a manual ROI method (ICC(2,1) > 0.78). These values were significantly correlated with mean manual N-values (p < 0.001).. Our new method shows sufficiently good agreement with the standard method and can provide a more objective metabolic index.

Topics: Adult; Algorithms; Brain Neoplasms; Carbon Radioisotopes; Female; Fluorodeoxyglucose F18; Glioma; Humans; Image Processing, Computer-Assisted; Male; Methionine; Middle Aged; Pattern Recognition, Automated; Positron-Emission Tomography; Radiopharmaceuticals; Reference Values

OBJECTIVE Diffusion MRI is attracting increasing interest for tissue characterization of gliomas, especially after the introduction of antiangiogenic therapy to treat malignant gliomas. The goal of the current study is to elucidate the actual magnitude of the correlation between diffusion MRI and cell density within the tissue. The obtained results were further extended and compared with metabolic imaging with

Topics: Brain Neoplasms; Cell Count; Diffusion Tensor Imaging; Glioma; Humans; Methionine; Positron-Emission Tomography; Predictive Value of Tests; Radiopharmaceuticals; Reproducibility of Results

Methylation status of the methyl-guanine methyltransferase (MGMT) promoter is associated with a favorable response to a DNA alkylating agent in high-grade gliomas. We analyzed PET scans of patients with high-grade gliomas to determine whether the MGMT methylation status affects the tumor metabolic characteristics.. Twenty-three patients with high-grade glioma, who were initially examined with 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) PET, were retrospectively enrolled. MET and FDG PET images were coregistered to each other and quantitative uptake of MET or FDG was assessed using tumor-to-normal uptake ratio of the cortex (TNR). TNRs for MET and FDG PET were compared between the two groups classified by MGMT promoter methylation status.. Maximum TNR(FDG) of the MGMT methylated group was significantly higher than that of the MGMT unmethylated group (1.80±0.90 vs. 1.29±0.19; P=0.02). The MGMT methylated group also showed a trend for increased mean TNRFDG compared with the unmethylated group (0.85±0.21 vs. 0.72±0.11; P=0.10). There was no significant difference in TNR(MET) between the groups. In subgroup analyses with WHO grade 3 and 4, a trend for higher maximum TNR(FDG) was found in the MGMT methylated group compared with the unmethylated group.. The MGMT methylated group showed higher glucose metabolism compared with the unmethylated group, whereas MET uptake did not show a significant difference. This suggests that MGMT methylation in high-grade gliomas could affect the tumor glucose metabolism. Thus, MGMT methylation status can cause a discrepancy in the prognostic prediction of high-grade gliomas by FDG PET, especially in patients scheduled for DNA alkylating chemotherapeutics.

Topics: Adolescent; Adult; Aged; Child; DNA Methylation; Female; Fluorodeoxyglucose F18; Glioma; Humans; Male; Methionine; Middle Aged; Neoplasm Grading; O(6)-Methylguanine-DNA Methyltransferase; Positron-Emission Tomography; Prognosis; Promoter Regions, Genetic; Retrospective Studies; Young Adult

(11)C-methionine (MET) PET is an established diagnostic tool for glioma. Studies have suggested that MET uptake intensity in the tumor is a useful index for predicting patient outcome. Because MET uptake is known to reflect tumor expansion more accurately than MRI, we aimed to elucidate the association between volume-based tumor measurements and patient prognosis.. The study population comprised 52 patients with newly diagnosed glioma who underwent PET scanning 20 min after injection of 370 MBq MET. The tumor was contoured using a threshold of 1.3 times the activity of the contralateral normal cortex. Metabolic tumor volume (MTV) was defined as the total volume within the boundary. Total lesion methionine uptake (TLMU) was defined as MTV times the mean standardized uptake value (SUVmean) within the boundary. The tumor-to-normal ratio (TNR), calculated as the maximum standardized uptake value (SUVmax) divided by the contralateral reference value, was also recorded. All patients underwent surgery (biopsy or tumor resection) targeting the tissue with high MET uptake. The Kaplan-Meier method was used to estimate the predictive value of each measurement.. Grade II tumor was diagnosed in 12 patients (3 diffuse astrocytoma, 2 oligodendroglioma, and 7 oligoastrocytoma), grade III in 18 patients (8 anaplastic astrocytoma, 6 anaplastic oligodendroglioma, and 4 anaplastic oligoastrocytoma), and grade IV in 22 patients (all glioblastoma). TNR, MTV and TLMU were 3.1 ± 1.2, 51.6 ± 49.9 ml and 147.7 ± 153.3 ml, respectively. None of the three measurements was able to categorize the glioma patients in terms of survival when all patients were analyzed. However, when only patients with astrocytic tumor (N = 33) were analyzed (i.e., when those with oligodendroglial components were excluded), MTV and TLMU successfully predicted patient outcome with higher values associated with a poorer prognosis (P < 0.05 and P < 0.01, respectively), while the predictive ability of TNR did not reach statistical significance (P = NS).. MTV and TLMU may be useful for predicting outcome in patients with astrocytic tumor.

Topics: Adult; Aged; Aged, 80 and over; Brain Neoplasms; Female; Glioma; Humans; Male; Methionine; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; Radiopharmaceuticals; Tumor Burden

11C-Methionine (MET) PET and diffusion-weighted (DW) MRI are commonly used for evaluation of gliomas. We assessed the correlation between MET uptake and diffusion restriction measured on DW MRI in glioma.. Thirty-one patients with gliomas, who were initially examined with MET PET and DW MRI, were enrolled retrospectively. MET PET and apparent diffusion coefficient (ADC) images were coregistered to each other, using rigid-body transformation. Tumor-to-normal count density ratio of the cortex (TNR) and normalized apparent diffusion coefficient (nADC) value were measured for each voxel on the MET PET and ADC map. The maximum TNR (TNRmax) and minimum nADC (nADCmin) were obtained for each tumor. Correlations between those parameters were evaluated.. The TNRmax and nADCmin values of a glioma were significantly correlated (r=-0.42). TNRmax and nADCmin were significantly correlated with glioma grades. Furthermore, TNRmax and nADCmin showed a trend for correlation with the Ki-67 index. We analyzed the correlation between voxel-based TNR and ADC within a tumor and observed no correlation between them. Regions with high MET uptake did not correspond with regions with low nADC.. We found a negative correlation between TNRmax and nADCmin for each glioma; however, MET uptake and ADC within a tumor were independent of each other and were heterogeneous. The two parameters represent different biological features; thus, as a comprehensive approach, MET PET and DW MRI might have a complementary role in the characterization of gliomas.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Diffusion Magnetic Resonance Imaging; Female; Glioma; Humans; Male; Methionine; Middle Aged; Positron-Emission Tomography; Young Adult

Positron emission tomography (PET) with 11C-methionine (11C-methionine PET/CT) is a new technique used to evaluate primary central nervous system (CNS) tumors. We describe our experience regarding the first 4 patients with glial tumors and 11C-methionine PET/CT. This is a descriptive, observational and prospective study of 4 patients between 38-50 years of age, with different gliomas (WHO classification). MRI and 11C-methionine PET/CT were performed in all cases. Case 1, gliomatosis cerebri grade II post-radiotherapy. Case 2, oligodendroglioma grade II diagnosed and treated with radiotherapy in 1993. Case 3, glioblastoma grade IV post-radiotherapy + temozolomide. Case 4, anaplastic oligoastrocytoma grade III post-radiotherapy + temozolomide. The pattern of 11C-methionine uptake compared with MRI showed tumor progression in cases 1, 3 and 4, and in case 2 showed uptake although the final diagnosis was pseudoprogression. Unlike 18fluordeoxiglucose PET/TC, 11C-methionine uptake in normal brain tissue and pseudoprogression is low, and gliomas are displayed as metabolically active areas. The 11C-methionine PET/CT provided valuable information on the tumoral behavior and extension, although in one case presented did not differentiate tumor progression from pseudoprogression. 11C-methionine PET/CT could be a useful tool in the study and follow-up to patients with gliomas.

Topics: Adult; Astrocytoma; Brain Neoplasms; Female; Glioma; Gliosarcoma; Humans; Male; Methionine; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Tomography, X-Ray Computed

Topics: Adult; Brain Infarction; Brain Neoplasms; Cerebral Veins; Diagnosis, Differential; Female; Glioma; Humans; Methionine; Positron-Emission Tomography; Radiopharmaceuticals

The aim of the study was to evaluate the volumetric integration patterns of standard MRI and (11)C-methionine positron emission tomography (PET) images in the surgery planning of gliomas and their relationship to the histological grade.. We studied 23 patients with suspected or previously treated glioma who underwent preoperative (11)C-methionine PET because MRI was imprecise in defining the surgical target contour. Images were transferred to the treatment planning system, coregistered and fused (BrainLAB). Tumour delineation was performed by (11)C-methionine PET thresholding (vPET) and manual segmentation over MRI (vMRI). A 3-D volumetric study was conducted to evaluate the contribution of each modality to tumour target volume. All cases were surgically treated and histological classification was performed according to WHO grades. Additionally, several biopsy samples were taken according to the results derived either from PET or from MRI and analysed separately.. Fifteen patients had high-grade tumours [ten glioblastoma multiforme (GBM) and five anaplastic), whereas eight patients had low-grade tumours. Biopsies from areas with high (11)C-methionine uptake without correspondence in MRI showed tumour proliferation, including infiltrative zones, distinguishing them from dysplasia and radionecrosis. Two main PET/MRI integration patterns emerged after analysis of volumetric data: pattern vMRI-in-vPET (11/23) and pattern vPET-in-vMRI (9/23). Besides, a possible third pattern with differences in both directions (vMRI-diff-vPET) could also be observed (3/23). There was a statistically significant association between the tumour classification and integration patterns described above (p < 0.001, κ = 0.72). GBM was associated with pattern vMRI-in-vPET (9/10), low-grade with pattern vPET-in-vMRI (7/8) and anaplastic with pattern vMRI-diff-vPET (3/5).. The metabolically active tumour volume observed in (11)C-methionine PET differs from the volume of MRI by showing areas of infiltrative tumour and distinguishing from non-tumour lesions. Differences in (11)C-methionine PET/MRI integration patterns can be assigned to tumour grades according to the WHO classification. This finding may improve tumour delineation and therapy planning for gliomas.

Topics: Adolescent; Adult; Aged; Female; Glioma; Humans; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Male; Methionine; Middle Aged; Neoplasm Grading; Positron-Emission Tomography; Time Factors; Tumor Burden; Young Adult

The linear correlation between (11)C-methionine PET and tumor cell density is not well conserved at the tumor border in glioma. A novel imaging analysis method, voxelwise (18)F-FDG-(11)C-methionine PET decoupling analysis (decoupling score), was evaluated to determine whether it could be used to quantitatively assess glioma cell infiltration in MRI-nonenhancing T2 hyperintense lesions.. Data collection was performed in a prospective fashion. Fifty-four MRI-nonenhancing T2 hyperintense specimens were stereotactically obtained from 23 glioma patients by intraoperative navigation guidance. The decoupling score and tumor-to-normal tissue (T/N) ratio of (11)C-methionine PET were calculated at each location. Correlations between the tumor cell density at these lesions, decoupling score, and T/N ratio of (11)C-methionine PET were then evaluated.. Both the decoupling score and the T/N ratio showed a linear correlation with tumor cell density at these specimens (R(2) = 0.52 and 0.53, respectively). Use of the decoupling score (cutoff = 3.0) allowed the detection of specimens with a tumor cell density of more than 1,000/mm(2), with a sensitivity and specificity of 93.5% and 87.5%, respectively, whereas conventional (11)C-methionine PET (cutoff = 1.2 in T/N ratio) was able to detect with a sensitivity and specificity of 87.0% and 87.5%, respectively. Reconstructed images (decoupling map) using the decoupling score enabled the visualization of glioma lesions that were difficult to visualize by (11)C-methionine PET alone.. The decoupling score showed better performance in detecting glioma cell infiltration than (11)C-methionine uptake alone, thus suggesting that (18)F-FDG-(11)C-methionine uptake decoupling analysis is a powerful imaging modality for assessing glioma invasion.

Topics: Adult; Aged; Biological Transport; Brain; Cell Count; Female; Fluorodeoxyglucose F18; Glioma; Humans; Image Processing, Computer-Assisted; Linear Models; Magnetic Resonance Imaging; Male; Methionine; Middle Aged; Positron-Emission Tomography

The aim of this study was to compare the grading and prognostic value of l-[methyl-(11)C]-methionine ((11)C-MET) PET in glioma patients with (18)F-FDG PET and contrast-enhanced MRI.. Patients (n = 102) with histopathologically confirmed gliomas were followed up for an average of 34.6 ± 3.8 mo after PET. The median survival was 18 ± 4.7 mo in the high-grade glioma group and 58 ± 27 mo in the low-grade glioma group. Patients underwent (18)F-FDG PET, (11)C-MET PET, and MRI in the diagnostic and preoperative stage. The ratio of the mean standardized uptake value in the tumor to mean standardized uptake value in contralateral normal cortex (T/N ratio) was calculated. Kaplan-Meier survival analysis and ANOVA were performed.. T/N ratios for (11)C-MET PET and (18)F-FDG PET were significantly higher in high-grade gliomas than in low-grade gliomas (2.15 ± 0.77 vs. 1.56 ± 0.74, P < 0.001, and 0.85 ± 0.61 vs. 0.63 ± 0.37, P < 0.01, respectively). Median survival was 19 ± 5.4 mo in patients with a T/N ratio greater than 1.51 for (11)C-MET PET and 58 ± 26.7 mo in those with a T/N ratio less than 1.51 (P = 0.03). Among the LGGs, median survival was lower in patients with a mean T/N ratio greater than 1.51 for (11)C-MET PET (16 ± 10 mo; 95% confidence interval, 1-36 mo) than in those with a T/N ratio less than 1.51 (P = 0.04). No significant difference in survival in LGGs was based on (18)F-FDG uptake and MRI contrast enhancement.. (11)C-MET PET can predict prognosis in gliomas and is better than (18)F-FDG PET and MRI in predicting survival in LGGs.

Topics: Adult; Child; Contrast Media; Fluorodeoxyglucose F18; Glioma; Humans; Magnetic Resonance Imaging; Methionine; Neoplasm Grading; Positron-Emission Tomography; Prognosis; Retrospective Studies

Diffuse intrinsic brainstem gliomas (DIBSGs) in children remain difficult tumors to treat and have a very poor prognosis. Intensifying both chemotherapy and radiation programs have been attempted without success. Positron emission tomography (PET) has been used to differentiate benign from malignant tumors and may predict outcome.. To determine whether PET can characterize a specific metabolic pattern of DIBSGs and correlate this with patient survival.. We conducted a retrospective review of patients with DIBSGs and PET scans at diagnosis. Data for ¹⁸[F] fluorodeoxyglucose (FDG) and ¹¹C-methionine (CMET) PET scans were collected. Treatment and survival were reviewed.. We identified 30 patients with DIBSGs, 25 of whom had FDG and/or CMET PET scans. Scans showed both focal and generalized metabolic activity, and the patterns showed no correlation with survival. Patients with both FDG and CMET positive scans had a mean survival of 380 days, whereas those negative for both isotopes had a mean survival of 446 days.. There was no specific PET pattern identified in this DIBSG cohort but a trend toward improved survival was noted with absence of FDG and CMET metabolism. Metabolically active areas may suggest potential sites for biopsy. We believe that biopsy is essential for improving therapy for this patient population.

Topics: Adolescent; Brain Stem Neoplasms; Child; Child, Preschool; Female; Fluorodeoxyglucose F18; Glioma; Humans; Male; Methionine; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies

Topics: Female; Glioma; Humans; Methionine; Neoplasm Invasiveness; Positron-Emission Tomography; Recurrence

Multimodal imaging is one of the necessary steps in the treatment of malignant brain tumors, and use of magnetic resonance imaging (MRI) and positron emission tomography (PET) are the current gold standard technique for the morphological and biological assessment of malignant brain tumors. In addition, fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) and 11C-methionine PET are useful to determine the tumor border at the tumor and white matter interface. Although there is no question of their value, a universally accepted cut-off value to discriminate normal and abnormal tissue has not been established. In this study we attempted to calculate and determine the cut-off values in FA and 11C-methionine PET that will allow delineation of the tumor border at the tumor and white matter interface by combining these two modalities. We were able to determine individual cut-off values for 11 patients, and then found an average cut-off value in the T/N ratio of 11C-methionine PET of 1.27 and in FA of 0.26, values similar to those previously confirmed by histological study. Moreover, reconstructing images delineating the tumor border was possible combining these two imaging modalities. We propose that the combined analysis of DTI and 11C-methionine PET has the potential to improve tumor border imaging in glioma patients, providing important information for establishing neurosurgical strategies.

Topics: Adolescent; Adult; Aged; Algorithms; Anisotropy; Brain Neoplasms; Diffusion Magnetic Resonance Imaging; Female; Glioma; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Male; Methionine; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Subtraction Technique

Static imaging of amino acids does not allow differentiation of low versus high grade brain tumours. It has been shown that dynamic imaging of the amino acid analogue (18)F-fluoroethyltyrosine (FET) can achieve this goal. In many centres, (11)C-methionine (MET) is used for tumour imaging, but no clinical studies on the use of dynamic scanning for grading have been performed.. Thirty-four patients with primary brain glioma and histopathological confirmation were retrospectively studied using 40 min dynamic MET-PET with 220 MBq 11C-methionine. In relation to histopathological grading, various metabolic indices and temporal parameters as documented by Poepperl et al. (JNM 2006;47:393-403) were analyzed.. None of the evaluated static or temporal parameters allowed discrimination between high and low grade tumours. On average, low grade tumours showed washout after the initial uptake maximum, while both increases and decreases were seen for high grade tumours. Only the relative early versus late uptake ratio showed a trend towards significance (-0.16 +/- 0.17 for low grade versus 0.01 +/- 0.25 for high grade; p = 0.07).. Unlike FET-PET, the uptake characteristics of MET-PET do not allow classification of low and high grade tumours on an individual patient basis. Since literature data indicate that both tracers have a similar performance regarding biopsy location, tumour delineation, and detection of recurrence, FET-PET should be advocated over MET-PET as its uptake mechanism also allows noninvasive grading in glioma.

Topics: Adolescent; Adult; Brain Neoplasms; Child; Female; Glioma; Humans; Male; Methionine; Neoplasm Staging; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity

18F-fluorodeoxyglucose (FDG) and 11C-methionine (MET) PET imaging studies allow the investigation of metabolism and amino acid transport in brain tumours. Their (relative) usefulness and prognostic value in suspected recurrence or progression of primary brain tumours after previous therapy is an issue of debate. The aim of this study was to compare directly both radioligands in this setting.. Cerebral uptake of FDG and MET was determined sequentially on the same day in 30 patients (21 males, nine females; age 40.4+/-15.6 years), on average 4.0 years (range 0.1-18) after therapy for a primary brain tumour (23 grade II-IV astrocytomas, four oligodendrogliomas and three mixed oligo-astrocytomas). Images were acquired on a Siemens HR+ dedicated PET camera. Two observers scored FDG and MET scans independently. Semi-quantitative indices defined by the tumour (maximum)-to-background ratio were calculated based on manual ROI delineation and by using MET ROIs for FDG after automated co-registration. Patient follow-up was conducted until the last contact with inconspicuous clinical findings (average 41 months, range 12-62 months after PET) [(n=10)] or until death (n=20).. Overall median survival was 15.0 months. MET showed pathologically increased uptake in 28/30 scans, and FDG in 17/30. The inter-observer agreement was 100% for MET and 73% for FDG. Using Kaplan-Meier survival analysis, significant differences were found for both FDG (cut-off 0.8, log-rank p=0.007) and MET (cut-off 2.2, log-rank p=0.014). The combination of FDG and MET information resulted in the highest prognostic accuracy (p=0.003), while MET alone was the best prognostic predictor in the subgroup of patients with primary astrocytoma (n=23).. FDG and MET PET studies provide complementary prognostic information in patients with suspected brain tumour recurrence or progression after primary therapy. MET is considered the single agent of choice in the evaluation of these patients because of its sensitivity and clearer delineation of the suspected recurrence.

Topics: Adolescent; Adult; Aged; Belgium; Brain Neoplasms; Child; Female; Fluorodeoxyglucose F18; Glioma; Humans; Male; Methionine; Middle Aged; Neoplasm Recurrence, Local; Observer Variation; Positron-Emission Tomography; Prevalence; Prognosis; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; Risk Assessment; Risk Factors; Sensitivity and Specificity; Survival Analysis

The purpose of this study was to compare the prognostic value of 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in glioma patients.. The study population comprised 47 patients with gliomas (19 glioblastoma, 28 others). Pretreatment magnetic resonance imaging, MET PET and FDG PET were performed within a time interval of 2 weeks in all patients. The uptake ratio and standard uptake values were calculated. Univariate and multivariate analyses were done to determine significant prognostic factors. Ki-67 index was measured by immunohistochemical staining, and compared with FDG and MET uptake in glioma.. Among the several clinicopathological prognostic factors, tumour pathology (glioblastoma or not), age (> or =60 or <60 years), Karnofsky performance status (KPS) (> or =70 or <70) and MET PET (higher uptake or not compared with normal cortex) were found to be significant predictors by univariate analysis. In multivariate analysis, tumour pathology, KPS and MET PET were identified as significant independent predictors. The Ki-67 proliferation index was significantly correlated with MET uptake (r=0.64), but not with FDG uptake.. Compared with FDG PET in glioma, MET PET was an independent significant prognostic factor and MET uptake was correlated with cellular proliferation. MET PET may be a useful biological prognostic marker in glioma patients.

Topics: Brain Neoplasms; Female; Fluorodeoxyglucose F18; Glioma; Humans; Korea; Male; Methionine; Middle Aged; Positron-Emission Tomography; Prevalence; Prognosis; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; Risk Assessment; Risk Factors; Sensitivity and Specificity; Survival Analysis

Neuroimaging-guided stereotactic biopsy procedures are commonly used for diagnosis of gliomas. A number of the imaging modalities currently in use are not reliable enough in depicting these tumors. The authors developed 18F-choline and 11C-choline as tumor imaging agents for positron emission tomography (PET) scanning, and used them to visualize gliomas prior to stereotactic biopsy procedures.. The PET studies were performed in 12 patients who were thought to be affected by gliomas observed on computerized tomography and magnetic resonance images. The 18F- and 11C-choline were injected separately, and the PET scanning was started 5 and 20 minutes postinjection. The PET scans gave quantitative information about the distribution of 18F- and 11C-choline in the brain. The tumor uptake was constant between 5 and 20 minutes with both agents. Stereotactic biopsy sampling was performed to obtain tissues from the most radioactive areas on the PET scan; histological diagnoses were made using these tissues. The results were as follows: oligodendroglioma was found in two patients, astrocytoma in one, anaplastic astrocytoma in two, and glioblastoma in seven.. The uptake of contrast agents was always low in low-grade gliomas, and the uptake in high-grade glioma was always high. The tumor/normal (T/N) ratio of 18F-choline was 10.5:12 in anaplastic astrocytoma and 13.2:21 in glioblastoma. The 18F-choline yielded slightly superior results compared with 11C-choline with regard to the T/N ratio. In one case of oligodendroglioma the tumor showed no uptake of 18F- and 11C-choline. With this exception, the PET scans of gliomas in which 18F- and 11C-choline contrast agents were added would guide the approach to the most malignant areas for stereotactic biopsy sampling.

Topics: Adolescent; Adult; Aged; Biopsy; Brain Neoplasms; Choline; Contrast Media; Female; Glioma; Humans; Male; Methionine; Middle Aged; Preoperative Care; Radiopharmaceuticals; Stereotaxic Techniques; Surgery, Computer-Assisted; Tomography, Emission-Computed

Cerebral gliomas may cause a reduction of glucose metabolism in the cerebellum contralateral to the tumor side (crossed cerebellar diaschisis, CCD). We investigated whether CCD is related to tumor localization, histological grade, size and tumor biochemistry. Cerebellar glucose metabolism was measured in 44 glioma patients and 15 healthy subjects using positron emission tomography and [18F]fluorodeoxyglucose (FDG). CCD was determined by calculating an asymmetry index of cerebellar glucose metabolism. Further, the tumor uptake of FDG and [11C]methionine (MET) was also assessed, and was expressed as ratio of normalized tracer uptake in tumor over contralateral cortex (T/C). Frontal lobe tumors were associated with highest CCD values. For these tumors, CCD was higher in malignant (-11.8+/-9.9%) than in low-grade (-4.3+/-4.1%) gliomas (P=0.010). In addition, frontal lobe tumors showed increasing CCD values with increasing size. In tumors of the parietal or temporal lobe, CCD was less marked or absent. T/C ratios of tumor tracer uptake were higher in malignant than in low-grade gliomas, but were not correlated with CCD. Our data indicate that the magnitude of CCD is mainly determined by tumor localization and size, the latter being associated with tumor grade. These findings raise the question whether CCD provides a measure of expansion or progression particularly in low-grade tumors of the frontal lobe.

Topics: Adult; Animals; Brain Neoplasms; Cerebellum; Fluorodeoxyglucose F18; Glioma; Glucose; Humans; Methionine; Middle Aged; Radiopharmaceuticals; Retrospective Studies; Tomography, Emission-Computed

This study evaluates the usefulness of PET for the preoperative evaluation of brain gliomas and methods of quantification of PET results.. Fifty-four patients with brain gliomas were studied by PET with 18F-fluorodeoxyglucose (FDG) (n = 45) and/or 11C-methionine (MET) (n = 41) before any treatment. Results of visual analysis, calculation of glucose consumption and five tumor-to-normal brain ratios for both tracers were correlated with two histologic grading systems and with follow-up.. Visual analysis (for FDG) and tumor-to-mean cortical uptake (T/MCU) ratio proved to be the best tools for the evaluation of PET results. Methionine was proven to be better than FDG at delineating low-grade gliomas. Tumor-to-mean cortical uptake ratios for FDG and MET were clearly correlated (r = 0.78), leading to the equation T/MCU(FDG) = 0.4 x T/MCU(MET). We showed a good correlation between FDG PET and histologic grading. MET uptake could not differentiate between low-grade and anaplastic astrocytomas but was significantly increased in glioblastomas. Low-grade oligodendrogliomas exhibited high uptake of FDG and MET, probably depending more on oligodendroglial cellular differentiation than on proliferative potential. Uptake was decreased in anaplastic oligodendrogliomas, probably due to dedifferentiation. Care must be taken with peculiar histologic subgroups, i.e., juvenile pilocytic astrocytomas and oligodendrogliomas, because of a discrepancy between high PET metabolism and low proliferative potential (good prognosis). Both tracers proved useful for the prediction of survival prognosis. Methionine proved slightly superior to FDG for predicting the histologic grade and prognosis of gliomas, despite the impossibility of differentiation between Grades II and III astrocytomas with MET. This superiority of MET could be explained by patient sampling (low number of Grade III gliomas submitted to examination with both tracers). The combination of both tracers improved the overall results compared to each tracer alone.. Both tracers are useful for the prediction of the histologic grade and prognosis. The apparent superiority of MET over FDG could be due to the small number of Grade III gliomas studied with both tracers.

Topics: Brain; Brain Neoplasms; Carbon Radioisotopes; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Glioma; Humans; Male; Methionine; Middle Aged; Radiopharmaceuticals; Survival Analysis; Tomography, Emission-Computed

A 57-yr-old woman suffering from light movement disorder of the left arm and hand was referred for 18F-Dopa PET. The PET study not only proved asymmetrically reduced dopamine uptake in the putamen (influx constant Ki right 0.0064/min, left 0.0086) but also revealed pathologically increased 18F-Dopa accumulation in the right frontal lobe. Further PET examinations demonstrated increased 11C-methionine uptake and low glucose metabolism in this right frontal region. MRI and 1H-MRSI showed a heterogeneous lesion with reduced N-acetyl-aspartate and increased choline and lactate, suggesting a mixed, low-grade glioma. In 15O-water studies, during intentional movements of one hand the respective motor areas were identified, indicating asymmetries due to the mass occupying lesion. The tumor could be removed in open surgery, thus sparing the motor areas; a mild postoperative motor deficit resolved to the presurgical state. Histology confirmed the diagnosis of a grade 2 oligo-astrocytoma. This case impressively demonstrates that 18F-Dopa can be used as an amino acid tracer for brain tumor detection in addition to its established application to assess aromatic acid decarboxylase activity.

Topics: Brain; Brain Neoplasms; Deoxyglucose; Dihydroxyphenylalanine; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Glioma; Glucose; Humans; Magnetic Resonance Imaging; Methionine; Middle Aged; Oxygen Radioisotopes; Tomography, Emission-Computed; Water