Metabolic Assessment of Gliomas Using 11C-Methionine, [18F] Fluorodeoxyglucose, and 11C-Choline Positron-Emission Tomography (original) (raw)
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Journal of the Neurological Sciences, 2006
The treatment of the glioma patient depends on the nature of the lesion and on the aggressiveness of the tumor. The management of gliomas continues to be a challenging task, because morphological neuroimaging techniques do not always differentiate them from nontumoral lesions or high grade tumors from low grade lesions. Positron Emission Tomography (PET) offers the possibility of the in vivo quantitative characterization of brain tumors. Despite decades of useful application of PET in the clinical monitoring of gliomas, no consensus has been reached on the most effective image analysis approach for providing the best diagnostic performance under heavy-duty clinical diagnostic circumstances. The main objective of the present study was to find and validate optimal semi-quantitative search strategies for metabolic PET studies on gliomas, with special regard to the optimization of those metabolic tracer uptake ratios most sensitive in predicting histologic grade and prognosis. 11 C-Methionine ( 11 C-Met, n = 50) and/or 18 F-Fluorodeoxyglucose ( 18 F-FDG, n = 33) PET measurements were performed in 59 patients with primary and recurrent brain gliomas (22 high grade and 37 low grade tumors) in order to correlate the biological behavior and 11 C-Met/ 18 F-FDG uptake of tumors. Data were analyzed by region-of-interests (ROI) methods using standard uptake value calculation. Different ROI defining strategies were then compared with each other for two of the most commonly used metabolic radiotracers, 18 F-FDG and 11 C-Met, in order to determine their usefulness in grading gliomas. The results were compared to histological data in all patients. Both ANOVA and receiver operating characteristic (ROC) analysis indicated that the performance of 18 F-FDG was superior to that of 11 C-Met for most of the ratios. 18 F-FDG is therefore suggested as the tracer of choice for noninvasive semiquantitative indicator of histologic grade of gliomas. 11 C-Methionine has been suggested as a complimentary tracer, useful in delineating the extent of the tumor. The best diagnostic performance was obtained by calculating the ratio of the peak 18 F-FDG uptake of the tumor to that of white matter ( p < 0.001; ANOVA). This metabolic tracer uptake ratio is therefore suggested as an easily obtained semi-quantitative PET indicator of malignancy and histological grade in gliomas. D
Methyl-L-11C-methionine PET as a diagnostic marker for malignant progression in patients with glioma
Journal of Nuclear …, 2009
Methyl-L-11 C-methionine (11 C-MET) PET has been shown to detect brain tumors with a high sensitivity and specificity. In this study, we investigated the potential of 11 C-MET PET to noninvasively detect tumor progression in patients with gliomas. Moreover, we analyzed the relationship between changes in 11 C-MET uptake on PET and changes in various molecular immunohistochemical markers during progression of gliomas. Methods: Twenty-four patients with histologically proven glioma were investigated repeatedly with 11 C-MET PET. 11 C-MET uptake was determined for a circular region of interest. Histologic and molecular analyses for tumor progression were performed after open surgery and stereotactic biopsy, respectively. Results: In patients with malignant progression, the mean increase in 11 C-MET uptake was 54.4% (SD, 45.5%; range, 3.1%2162.2%), whereas in patients without a change in tumor grade, mean 11 C-MET uptake did not significantly change (3.9%; SD, 13.7%; range, 224.4% to 26.3%). The difference in the change in 11 C-MET uptake between the group with malignant progression and the group without malignant progression was highly significant (P , 0.001). Receiver-operating-curve analysis revealed a sensitivity of 90% and a specificity of 92.3% for the detection of malignant transformation by an increase in 11 C-MET uptake of more than 14.6%. Increased 11 C-MET uptake of more than 14.6% was indicative of malignant progression in all but 3 leave-one-out iterations. A detailed immunohistochemical analysis demonstrated a significant correlation between changes in 11 C-MET uptake and the expression of vascular endothelial growth factor. Conclusion: These data suggest that 11 C-MET-PET represents a noninvasive method to detect malignant progression in patients with gliomas. Moreover, the increase in 11 C-MET uptake during malignant progression is reflected by an increase in angiogenesis-promoting markers as vascular endothelial growth factor.
11C-methionine PET for differential diagnosis of low-grade gliomas
Neurology, 1998
Article abstract-Management of low-grade gliomas continues to be a challenging task, because CT and MRI do not always differentiate from nontumoral lesions. Furthermore, tumor extent and aggressiveness often remain unclear because of a lack of contrast enhancement. Previous studies indicated that large neutral amino acid tracers accumulate in most brain tumors, including low-grade gliomas, probably because of changes of endothelial and blood-brain barrier function. We describe 'lc-methionine uptake measured with PET in a series of 196 consecutive patients, most of whom were studied because of suspected low-grade gliomas. Uptake in the most active lesion area, relative to contralateral side, was significantly different among high-grade gliomas, low-grade gliomas, and chronic or subacute nontumoral lesions, and this difference was independent from contrast enhancement in CT or MRI. Corticosteroids had no significant effect on methionine uptake in low-grade gliomas but reduced uptake moderately in high-grade gliomas. Differentiation between gliomas and nontumoral lesions by a simple threshold was correct in 79%. Recurrent or residual tumors had a higher
PET for diagnosis and therapy of brain tumors
Médecine Nucléaire, 2011
Main contribution of PET in the management of brain tumors is at the therapeutic level. Specific reasons explain this role of molecular imaging in the therapeutic management of brain tumors, especially gliomas. Gliomas are by nature infiltrating neoplasms and the interface between tumor and normal brain tissue may not be accurately defined on CT and MRI. Also, gliomas are often histologically heterogeneous with anaplastic areas evolving within a low-grade tumor, and the contrast-enhancement on CT or MRI does not represent a good marker for anaplastic tissue detection. Finally, assessment of tumor residue, recurrence or progression may be altered by different signals related to inflammation or adjuvant therapies, even on contrast-enhanced CT and MRI. These limitations of the conventional neuroimaging in delineating tumor and detecting anaplastic tissue lead to potential inaccuracy in lesion targeting at different steps of the management (diagnostic, surgical, and post-therapeutic stages). Molecular information provided by PET has proved helpful to supplement morphological imaging data in this context. 18 F-FDG (FDG) and amino-acid tracers such as 11 C-methionine (MET), provides complementary metabolic data that are independent from the anatomical MR information. These tracers help in the definition of glioma extension, in the detection of anaplastic areas and in the postoperative follow-up. Additionally, PET data have an independent prognostic value. To take advantage of PET data in glioma treatment, PET might be integrated in the planning of imageguided biopsies, radiosurgery and resection.
A Combined Study with 18F-FDG and 11C-Methionine Dynamic PET for the Grading of Brain Gliomas
2020
Purpose: Conventional MRI based on contrast enhancement and T2/FLAIR is often not su cient in differentiating grade II from grade III and grade III from grade IV diffuse gliomas. Here we assessed advanced metabolic imaging using two well characterized PET tracers, namely 18 F-FDG and 11 C-Methionine. Methods: In this prospective study, 39 patients were enrolled with diffuse gliomas of grades II, III or IV underwent dynamic [ 18 F]-FDF-PET and [ 11 C]-Methionine. The rst minutes were taken into account Results: The use of 11 C-Methionine provided signi cant differences between the different histologic subgroups with a higher number of parameters than did the use of 18 F-FDG. The most informative parameter is T/Np (T/N at the peak of the rst maximum) with 11 C-Methionine. Conclusion: The study of the rst minute passage of 18 F-FDG and/or 11 C-Methionine through the tumor and healthy tissues in brain gliomas could not only allow improving the identi cation of the different glioma grades, but also to shorten the time spent by the patients under the camera. In case of using one tracer, methionine still would be the best choice. Otherwise, the use of 18 F-FDG and SUVр (SUV at the peak of the rst maximum) would provide results likely comparable to methionine T/N index.
ISRN Oncology, 2014
We investigated the sensitivity and specificity of [ 11 C]-methionine positron emission tomography ([ 11 C]-MET PET) in the management of glioma patients. We retrospectively analysed data from 53 patients with primary gliomas (16 low grade astrocytomas, 15 anaplastic astrocytomas and 22 glioblastomas) and Karnofsky Performance Status (KPS) > 70. Patients underwent [ 11 C]-MET PET scans ( = 249) and parallel contrast-enhanced MRI ( = 193) and/or CT ( = 113) controls. In low grade glioma patients, MRI or CT findings associated with [ 11 C]-MET PET additional data allowed discrimination residual disease from postsurgical changes in 96.22% of these cases. [ 11 C]-MET PET early allowed detection of malignant progression from low grade to anaplastic astrocytoma with high sensitivity (91.56%) and specificity (95.18%). In anaplastic astrocytomas, we registered high sensitivity (93.97%) and specificity (95.18%) in the postoperative imaging and during the followup of these patients. In GBM patients, CT and/or MRI scans with additional [ 11 C]-MET PET data registered a sensitivity of 96.92% in the postsurgical evaluation and in the tumour assessment during temozolomide therapy. A significant correlation was found between [ 11 C]-MET mean uptake index and histologic grading ( < 0.001). These findings support the notion that complementary information derived from [ 11 C]-MET PET may be helpful in postoperative and successive tumor assessment of glioma patients.
Imaging gliomas with positron emission tomography and single-photon emission computed tomography
Seminars in Nuclear Medicine, 2003
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-2deoxy-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.
EJNMMI Research, 2017
Background: We investigated the relationship between metabolic activity and histological features of gliomas using fluorine-18α-methyltyrosine (18 F-FAMT) positron emission tomography (PET) compared with fluorine-18 fluorodeoxyglucose (18 F-FDG) PET in 38 consecutive glioma patients. The tumor to normal brain ratios (T/N ratios) were calculated, and the relationships between T/N ratio and World Health Organization tumor grade or MIB-1 labeling index were evaluated. The diagnostic values of T/N ratios were assessed using receiver operating characteristic (ROC) curve analyses to differentiate between high-grade gliomas (HGGs) and low-grade gliomas (LGGs). Results: Median T/N ratio of 18 F-FAMT PET was 2.85, 4.65, and 4.09 for grade II, III, and IV gliomas, respectively, with significant differences between HGGs and LGGs (p = 0.006). Both T/N ratio (p = 0.016) and maximum standardized uptake value (p = 0.033) of 18 F-FDG PET showed significant differences between HGGs and LGGs. ROC analysis yielded an optimal cutoff of 3.37 for the T/N ratio of 18 F-FAMT PET to differentiate between HGGs and LGGs (sensitivity 81%, specificity 67%, accuracy 76%, area under the ROC curve 0.776). Positive predictive value was 84%, and negative predictive value was 62%. T/N ratio of 18 F-FAMT PET was not correlated with MIB-1 labeling index in all gliomas, whereas T/N ratio of 18 F-FDG PET was positively correlated (r s = 0.400, p = 0.013). Significant positive correlation was observed between T/N ratios of 18 F-FDG and 18 F-FAMT (r s = 0.454, p = 0.004), but median T/N ratio of 18 F-FAMT PET was significantly higher than that of 18 F-FDG PET in all grades of glioma. Conclusions: The T/N ratio of 18 F-FAMT uptake has high positive predictive value for detection of HGGs. 18 F-FAMT PET had higher T/N ratio, with better tumor-normal brain contrast, compared to 18 F-FDG PET in both LGGs and HGGs. Therefore, 18 F-FAMT is a useful radiotracer for the preoperative visualization of gliomas.
Performance of 18F-FDG, 11C-Methionine, and 18F-FET PET for Glioma Grading
Clinical Nuclear Medicine, 2019
Purpose: Gliomas constitute the most frequent primary brain tumors. Glioblastoma, the most common and malignant glioma in adults, has dismal prognosis with any current therapy. On the other hand, low-grade gliomas, the second most common type of gliomas, are potentially curative with appropriate treatment. Methods: We conducted a meta-analysis to assess the performance of PET tracers with the best available evidence, namely, fluorodeoxyglucose (FDG), 11 C-methionine (MET), and 18 F-fluoroethyltyrosine (FET), in differentiating low-from high-grade gliomas. Results: Twenty-three studies with a total of 994 participants were included in this meta-analysis. The pooled sensitivities of both MET PET and FET PET were found to be significantly higher than of FDG PET (94%, 88%, and 63% respectively, P < 0.001). The pooled specificity of FDG PET was found to be significantly greater compared with both MET PET and FET PET (89%, 55%, and 57%, respectively; P = 0.002). Fluorodeoxyglucose PET was superior in terms of higher positive likelihood ratio values compared with both FET PET and MET PET. Conclusions: This meta-analysis indicated that both MET and FETwere superior to FDG in terms of sensitivity for identifying glioma grade.