Metabolic Assessment of Gliomas Using 11C-Methionine, [18F] Fluorodeoxyglucose, and 11C-Choline Positron-Emission Tomography (original) (raw)
Related papers
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.
Prognostic value of volume-based measurements on (11)C-methionine PET in glioma patients
European journal of nuclear medicine and molecular imaging, 2015
Purpose 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. Methods 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. Results 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). Conclusion MTV and TLMU may be useful for predicting outcome in patients with astrocytic tumor.
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.
11 C- l Methionine Positron Emission Tomography in the Clinical Management of Cerebral Gliomas
Molecular Imaging and Biology, 2008
Positron emission tomography (PET) using l-[methyl-11C]-methionine (MET) is the most popular amino acid imaging modality in oncology, although its use is restricted to PET centers with an in-house cyclotron facility. This review focuses on the role of MET–PET in imaging of cerebral gliomas. The biological background of tumor imaging with methionine is discussed with particular emphasis on cellular amino acid transport, amino acid utilization in brain, normal metabolism of methionine, and its alterations in cancer. The role of MET–PET in clinical management of cerebral gliomas in initial diagnosis, differentiation of tumor recurrence from radiation injury, grading, prognostication, tumor-extent delineation, biopsy planning, surgical resection and radiotherapy planning, and assessment of response to therapy is also reviewed in detail.
Role of PET in the management of gliomas: The radiopharmacist's and clinician's point of view
Médecine Nucléaire, 2015
Positron emission tomography (PET) using fluorodeoxyglucose (FDG), a metabolic imaging modality widely used in systemic cancer, was proposed as a valuable tool for obtaining additional data for diagnosis and better treatment of patients with glioma. Unfortunately physiological uptake of FDG is high in the brain and other radioligands have been developed for neuro-oncology explorations. Based on the point of view of a radiopharmacist and a neuro-oncologist, this review describes the compounds used to explore pathophysiological processes such as proliferation rate, amino acid transport, protein synthesis, hypoxia, and membrane biosynthesis in gliomas and discusses the clinical impact of PET neuroimaging in initial diagnosis, tumour grading, and response to chemotherapy or radiotherapy. Molecular imaging modalities will be compared with magnetic resonance (MR) tools as will be the usefulness of MR/PET multimodality imaging.
European Journal of Nuclear Medicine and Molecular Imaging, 2007
Background 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. Methods 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. Results 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). Conclusion 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.
European Journal of Nuclear Medicine and Molecular Imaging, 2012
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and its prognosis is significantly poorer than those of less malignant gliomas. Pathologically, necrosis is one of the most important characteristics that differentiate GBM from lower grade gliomas; therefore, we hypothesized that 18 F fluoromisonidazole (FMISO), a radiotracer for hypoxia imaging, accumulates in GBM but not in lower grade gliomas. We aimed to evaluate the diagnostic value of FMISO PET for the differential diagnosis of GBM from lower grade gliomas. Methods: This prospective study included 23 patients with pathologically confirmed gliomas. All the patients underwent FMISO PET and FDG PET within a week. FMISO images were acquired 4 hours after intravenous administration of 400 MBq of FMISO. Tracer uptake in the tumor was visually assessed. Lesion-to-normal tissue ratios and FMISO uptake volume were calculated. Results: Thirteen of the 23 glioma patients were diagnosed as having GBM (grade IV glioma in WHO classification 2007), and the others were diagnosed as having non-GBM (5 grade III and 4 grade II). In visual assessment, all the GBM patients showed FMISO uptake in the tumor greater than that in the surrounding brain tissues, whereas all the non-GBM patients showed FMISO uptake in the tumor equal to that in the surrounding brain tissues (p<0.001). One GBM patient was excluded 2 from FDG PET study because of hyperglycemia. All the GBM patients and 3 of the 9 (33 %) non-GBM patients showed FDG uptake greater than or equal to that in the gray matter. The sensitivity and specificity for diagnosing GBM were 100 % and 100 % for FMISO, and 100 % and 66 % for FDG, respectively. The lesion-to-cerebellum ratio of FMISO uptake was higher in GBM patients (2.74±0.60, range: 1.71-3.81) than in non-GBM patients (1.22±0.06, range: 1.09-1.29, p<0.001) with no overlap between the groups. The lesion-to-gray matter ratio of FDG was also higher in GBM patients (1.46±0.75, range: 0.91-3.79) than in non-GBM patients (1.07±0.62, range: 0.66-2.95, p<0.05); however, overlap of the ranges did not allow clear differentiation between GBM and non-GBM. Uptake volume of FMISO was larger in GBM (27.18±10.46 %, range: 14.02-46.67 %) than in non-GBM (6.07±2.50 %, range: 2.12-9.22 %, p<0.001). Conclusion: These preliminary data suggest that FMISO PET may distinguish GBM from lower grade gliomas.
Prediction of pathology and survival by FDG PET in gliomas
Journal of neuro-oncology, 2003
Despite being in use for nearly two decades, the utility of [18F]2-fluoro-2deoxy-D-glucose positron emission tomography (FDG PET) in the evaluation and treatment of brain tumors remains controversial. We retrospectively analyzed all patients with histologically proven gliomas, between the years 1990 and 2000, who underwent FDG PET studies at various stages of their treatment and who were followed till either death or for a minimum period of 1 year in an attempt to bring resolution to this controversy. All PET scans prior to 1997 were acquired on an ECAT 951/31 scanner in 2D. Scans since 1997 were obtained on a Siemens HR+ scanner in 3D mode. The majority of FDG PET scans were co-registered with the magnetic resonance imaging (MRI) scans to aid in diagnosis and therapy. Based on independent visual inspection, two board certified nuclear medicine physicians graded the highest activity level of the tumor using the metabolic grading: 0 = no uptake; 1 = uptake less or equal to normal whi...
PET imaging of brain astrocytoma with 1-11C-acetate
European Journal of Nuclear Medicine and Molecular Imaging, 2006
Purpose: The purpose of this study was to assess the use of 1-11 C-acetate (ACE) as a metabolic tracer for the detection and characterisation of astrocytomas. Methods: Positron emission tomography (PET) studies with ACE and 2-18 F-fluoro-2-deoxy-D-glucose (FDG) were performed sequentially in 26 patients with primary astrocytomas. Images were analysed by visual interpretation and determination of the tumour to cortex ratio (T/C ratio) and standardised uptake value (SUV). The tumour uptake was visually scored into three grades as compared with the contralateral cortex: clearly lower (-), almost equal (+) and clearly higher (++). Results: There were 85% of astrocytomas with ++ ACE uptake, 15% with + ACE uptake and none with -ACE uptake. Only 19% of astrocytomas had ++ FDG uptake. Thirty-seven percent of high-grade astrocytomas had + FDG uptake and 37% had -FDG uptake. The sensitivity and specificity of the FDG T/C ratio in discriminating high-grade from low-grade astrocytomas were 79% and 100%, respectively, at the cutoff value of 0.75. Using 2.33 as the cutoff value of the ACE T/C ratio, the sensitivity and specificity were 42% and 86%, respectively. FDG was better than ACE in discriminating high-grade from lowgrade astrocytomas. T/C ratios and SUVs of FDG uptake of tumours correlated with the histological grades, but those of ACE uptake did not.
[F-18]Fluciclovine PET discrimination between high- and low-grade gliomas
Background: The ability to accurately and non-invasively distinguish high-grade glioma from low-grade glioma remains a challenge despite advances in molecular and magnetic resonance imaging. We investigated the ability of fluciclovine (F) PET as a means to identify and distinguish these lesions in patients with known gliomas and to correlate uptake with Ki-67. Results: Sixteen patients with a total of 18 newly diagnosed low-grade gliomas (n = 6) and high grade gliomas (n = 12) underwent fluciclovine PET imaging after histopathologic assessment. Fluciclovine PET analysis comprised tumor SUVmax and SUVmean, as well as metabolic tumor thresholds (1.3*, 1.6*, 1.9*) to normal brain background (TBmax, and TBmean). Comparison was additionally made to the proliferative status of the tumor as indicated by Ki-67 values. Fluciclovine uptake greater than normal brain parenchyma was found in all lesions studied. Time activity curves demonstrated statistically apparent flattening of the curves fo...
The role of [18F]fluorodopa positron emission tomography in grading of gliomas
Journal of Neuro-Oncology
Purpose Gliomas are the most commonly occurring brain tumour in adults and there remains no cure for these tumours with treatment strategies being based on tumour grade. All treatment options aim to prolong survival, maintain quality of life and slow the inevitable progression from low-grade to high-grade. Despite imaging advancements, the only reliable method to grade a glioma is to perform a biopsy, and even this is fraught with errors associated with under grading. Positron emission tomography (PET) imaging with amino acid tracers such as [18F]fluorodopa (18F-FDOPA), [11C]methionine (11C-MET), [18F]fluoroethyltyrosine (18F-FET), and 18F-FDOPA are being increasingly used in the diagnosis and management of gliomas. Methods In this review we discuss the literature available on the ability of 18F-FDOPA-PET to distinguish low- from high-grade in newly diagnosed gliomas. Results In 2016 the Response Assessment in Neuro-Oncology (RANO) and European Association for Neuro-Oncology (EANO) ...
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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.
Journal of Neuro-Oncology, 2012
The clinical course of meningioma varies from case to case, despite similar characteristics on magnetic resonance (MR) imaging. Functional imaging including (11)C-methionine and (18)F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) has been widely studied for noninvasive preoperative evaluation of brain tumors. However, few reports have examined correlations between meningiomas and findings on (11)C-methionine and FDG PET. The objective of this study was to clarify the relationship between tumor characteristics and (11)C-methionine and FDG uptake in meningiomas. For 68 meningiomas in 51 cases, (11)C-methionine uptake was evaluated by measuring both mean and maximum tumor/normal (T/N) ratio for the whole area of the tumors. FDG uptake in 44 of those meningiomas was also analyzed. Tumor size was measured volumetrically, and tumor-doubling time was estimated. Histopathological evaluation was performed in 19 surgical cases. Mean and maximum T/N ratios of (11)C-methionine PET were significantly higher in skull-base lesions than in non-skull-base lesions. Correlations of mean and maximum T/N ratio of (11)C-methionine PET with tumor-doubling time, MIB-1 labeling index, microvessel density and World Health Organization grading were not significant. Mean T/N ratio of (11)C-methionine PET correlated significantly with tumor volume according to logarithm regression modeling (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001, R = 0.544). However, mean and maximum T/N ratio of FDG-PET correlated with none of the tumor characteristics described above. These results suggest that (11)C-methionine uptake correlates with tumor volume, but not with tumor aggressiveness.
Journal of Neuro-Oncology, 2012
Discriminating tumor infiltrative and vasogenic brain edema in malignant gliomas is important although challenging in clinical settings. This study challenged this issue by performing voxel-wise analysis of (18)F-fluorodeoxy glucose (FDG) and (11)C-methionine positron emission tomography (PET) in peritumoral brain edemas. The authors studied ten malignant glioma and nine meningioma patients with peritumoral brain edema. A voxel-wise analysis of FDG and (11)C-methionine PET was performed in order to quantify the correlation between uptake of these tracers in normal brain tissue and peritumoral brain edema. Decoupling score of the uptake of two tracers was calculated as the z-score from the estimated correlation between uptake of the two tracers in normal brain tissue. The decoupling score was also converted into images for visual inspection. Average decoupling score in the peritumoral brain edema was calculated and compared between those obtained from malignant gliomas and meningiomas. FDG and (11)C-methionine uptake showed a reproducible linear correlation in normal brain tissue. This correlation was preserved in peritumoral edema of meningioma, but not in that of malignant gliomas. In malignant gliomas, higher (11)C-methionine uptake compared to that estimated by the FDG uptake in normal brain tissue was observed, thus suggesting that decoupling was caused by tumor infiltration. Visual inspection of the decoupling score enabled discrimination of tumor infiltrative and vasogenic edema. The average decoupling scores of the peritumoral brain edema in malignant gliomas were significantly higher than those in meningiomas (2.9 vs. 0.7, P = 0.0003). As a conclusion, FDG/(11)C-methionine uptake decoupling score can be used for the discrimination of tumor infiltrative and vasogenic brain edema. The proposed method also suggests the possibility of accurately detecting tumor infiltration into brain tissues in gliomas, providing significant information for treatment planning and follow-up.
Is there a role for PET-CT and SPECT-CT in pediatric oncology?
Acta Radiologica, 2013
During the last decade, hybrid imaging has revolutionized nuclear medicine. Multimodal camera systems, integrating positron emission tomography (PET) or single photon emission computed tomography (SPECT) with computed tomography (CT) now combine the contrast provided by tumor-avid radioactive drugs with the anatomic precision of CT.
Magnetic Resonance in Medicine, 2011
13 C chemical shift images acquired following intravenous injection of hyperpolarized [1-13 C]pyruvate into rats with implanted C6 gliomas showed significant labeling of lactate within the tumors but not in surrounding brain tissue. Signal from pyruvate was observed in blood vessels above the brain and from other major vessels elsewhere in the rat head. Pyruvate was largely undetectable within the tumor or surrounding normal brain tissue. The ratio of hyperpolarized 13 C label in the injected pyruvate and endogenous lactate was decreased from 0.25 +/− 0.13 to 0.13 +/ − 0.08, (a reduction of 48%) at 96 h following whole brain irradiation with 15 Gy. These data suggest that hyperpolarized [1-13 C]pyruvate may be useful in detecting treatment response in gliomas, where the use of 18 FDG-PET is limited by the high background signals from normal brain tissue.
Cancers
Purpose: The prognostic evaluation of glioma recurrence patients is important in the therapeutic management. We investigated the prognostic value of 11C-methionine PET-CT (MET-PET) dynamic and semiquantitative parameters in patients with suspected glioma recurrence. Methods: Sixty-seven consecutive patients who underwent MET-PET for suspected glioma recurrence at MR were retrospectively included. Twenty-one patients underwent static MET-PET; 46/67 underwent dynamic MET-PET. In all patients, SUVmax, SUVmean and tumour-to-background ratio (T/B) were calculated. From dynamic acquisition, the shape and slope of time-activity curves, time-to-peak and its SUVmax (SUVmaxTTP) were extrapolated. The prognostic value of PET parameters on progression-free (PFS) and overall survival (OS) was evaluated using Kaplan–Meier survival estimates and Cox regression. Results: The overall median follow-up was 19 months from MET-PET. Recurrence patients (38/67) had higher SUVmax (p = 0.001), SUVmean (p = ...
Journal of neurology, neurosurgery, and psychiatry, 2016
Chromosome 1p/19q deletion is an established prognostic and predictive marker in the WHO grade III oligodendroglial tumours (OT). To estimate the genetic status preoperatively, the authors investigated the correlation between the uptake of (11)C-methionine in positron emission tomography (PET) and the 1p/19q status in grades II and III OT. We retrospectively reviewed 144 patients with gliomas who received (11)C-methionine PET. 66 cases with grades II-III oligodendrogliomas or oligoastrocytomas underwent fluorescence in situ hybridisation to determine the 1p/19q status. The tissue uptake of (11)C-methionine was expressed as the ratio of the maximum standardised uptake value (SUVmax) in tumour areas to the mean SUV (SUVmean) in the contralateral normal brain (tumour-to-normal tissue (T/N) ratio). The T/N ratio in (11)C-methionine PET was significantly higher in grade III OT than in grade II tumours. The mean T/N ratio of the grade II tumours without 1p/19q deletion was significantly h...
Annals of Nuclear Medicine, 2012
To systematically review published data on the role of positron emission tomography (PET) or PET/computed tomography (PET/CT) using either Carbon-11 (11 C) or Fluorine-18 (18 F) choline tracer in tumors other than prostatic cancer. A comprehensive literature search of studies published in PubMed/MEDLINE and Embase databases through January 2012 and regarding 11 C-choline or 18 F-choline PET or PET/CT in patients with tumors other than prostatic cancer was carried out. Fifty-two studies comprising 1800 patients were included and discussed. Brain tumors were evaluated in 15 articles, head and neck tumors in 6, thoracic tumors (including lung and mediastinal neoplasms) in 14, liver tumors (including hepatocellular carcinoma) in 5, gynecologic malignancies (including breast tumors) in 5, bladder and upper urinary tract tumors in 5, and musculoskeletal tumors in 7. Radiolabeled choline PET or PET/CT is useful to differentiate high-grade from low-grade gliomas and malignant from benign brain lesions, to early detect brain tumor recurrences and to guide the stereotactic biopsy sampling. The diagnostic accuracy of radiolabeled choline PET is superior compared to Fluorine-18 fluorodeoxyglucose (18 F-FDG) PET in this setting. Radiolabeled choline PET or PET/CT seems to be accurate in differential diagnosis between malignant and benign thoracic lesions and in staging lung tumors; nevertheless, a superiority of radiolabeled choline compared to 18 F-FDG has not been demonstrated in this setting, except for the detection of brain metastases. Few but significant studies on radiolabeled choline PET and PET/CT in patients with hepatocellular carcinoma (HCC) and musculoskeletal tumors are reported in the literature. The combination of radiolabeled choline and 18 F-FDG PET increases the detection rate of HCC. The diagnostic accuracy of radiolabeled choline PET or PET/CT seems to be superior compared to 18 F-FDG PET or PET/CT and conventional imaging methods in patients with bone and soft tissue tumors. Limited experience exists about the role of radiolabeled choline PET and PET/CT in patients with head and neck tumors, bladder cancer and gynecologic malignancies including breast cancer.
Neurosurgical Review, 2018
The aim of our study was to compare depicted pre-, intra-, and postoperative tumor volume of met-PET, perfusionweighed MRI (PWI), and Gd-DTPA MRI. Further, to assess their sensitivity and specificity in correlation with histopathological specimen. Inclusion criteria of the prospective study were histological confirmed glioblastoma (GB), age > 18, and eligible for gross total resection (GTR). Met-PET was performed before and after surgery. Gd-DTPA MRI and PWI were performed before, during, and after surgery. A combined 5-aminolevulinic acid (5-ALA) and iMRI-guided surgery was performed. Volumetric analysis was evaluated for all imaging modalities except for 5-ALA. A total of 59 navigated biopsies were taken. Sensitivity and specificity were calculated for Gd-DTPA MRI, PWI, met-PET, and 5-ALA according to the histology of specimen. Met-PET depicted significantly larger tumor volume before surgery (p = 0.01) compared to PWI and Gd-DTPI MRI. We found no significant difference in tumor volume between met-PET and PWI after surgery (p = 0.059). Both PWI and met-PET showed significantly larger tumor volume after surgery when compared to Gd-DTPA (p = 0.018 and p = 0.003, respectively). Intraoperative PWI reading was impaired in 33.3% due to artifacts. Met-PET showed the highest sensitivity for detection of GB with 95%. The lowest sensitivity was found with Gd-DTPA MRI (50%), while 5-ALA and intraoperative PWI showed similar results (69 and 67%). Met-Pet is the imaging modality with the highest sensitivity to detect a residual tumor in GB. Intraoperative PWI seems to have a synergistic effect to Gd-DTPA and 5-ALA. However, its value may be limited by artifacts. Both pre-and intraoperative PWI cannot substitute met-PET in tumor detection.
Journal of Neuroimaging, 2011
BACKGROUND AND PURPOSE We used L-[1-11 C]leucine (LEU) positron emission tomography (PET) to measure amino acid uptake in children with Sturge-Weber syndrome (SWS), and to relate amino acid uptake measures with glucose metabolism. METHODS LEU and 2-deoxy-2[ 18 F]fluoro-D-glucose (FDG) PET were performed in 7 children (age: 5 months-13 years) with unilateral SWS. Asymmetries of LEU uptake in the posterior brain region, underlying the angioma and in frontal cortex, were measured and correlated with glucose hypometabolism. Kinetic analysis of LEU uptake was performed in 4 patients. RESULTS Increased LEU standard uptake value (SUV, mean: 15.1%) was found in the angioma region in 6 patients, and smaller increases in LEU SUV (11.5%) were seen in frontal cortex in 4 of the 6 patients, despite normal glucose metabolism in frontal regions. High LEU SUV was due to both increased tracer transport (3/4 patients) and high protein synthesis rates (2/4). FDG SUV asymmetries in the angioma region were inversely related to LEU SUV asymmetries (r =-.83, P = .042). CONCLUSIONS Increased amino acid uptake in the angioma region and also in less affected frontal regions may provide a marker of pathological mechanisms contributing to chronic brain damage in children with SWS.
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.