Perfusion and diffusion MRI combined with 11C-methionine PET in the preoperative evaluation of suspected adult low-grade gliomas

Perfusion and diffusion magnetic resonance imaging (pMRI, dMRI) are valuable diagnostic tools for assessing brain tumors in the clinical setting. The aim of this study was to determine the correlation of pMRI and dMRI with ¹¹C-methionine positron emission tomography (MET PET) in suspected low-grade gliomas (LGG) prior to surgery. Twenty-four adults with suspected LGG were enrolled in an observational study and examined by MET PET, pMRI and dMRI. Histological tumor diagnosis was confirmed in 23/24 patients (18 gliomas grade II, 5 gliomas grade III). The maximum relative cerebral blood volume (rCBV_max) and the minimum mean diffusivity (MD_min) were measured in tumor areas with highest MET uptake (hotspot) on PET by using automated co-registration of MRI and PET scans. A clearly defined hotspot on PET was present in all 23 tumors. Regions with rCBV_max corresponded with hotspot regions in all tumors, regions with MD_min corresponded with hotspot regions in 20/23 tumors. The correlation between rCBV_max (r = 0.19, P = 0.38) and MD_min (r = ?0.41, P = 0.053) with MET uptake in the hotspot was not statistically significant. Taken into account the difficulties of measuring perfusion abnormalities in non-enhancing gliomas, this study demonstrates that co-registered MET PET and pMRI facilitates the identification of regions with rCBV_max. Furthermore, the lack of a clear positive correlation between tumor metabolism in terms of MET uptake and tumor vascularity measured as rCBV_max suggests that combined pMRI/PET provides complementary baseline imaging data in these tumors.     

Evaluation of children with craniopharyngioma using carbon-11 methionine PET prior to proton therapy

Background

Fluorine-18 (¹⁸F) fluorodeoxyglucose (FDG) positron emission tomography (PET) is limited in its evaluation of brain tumors due to the high basal activity of the cerebral cortex and white matter. Carbon-11 methionine (¹¹C MET) has little uptake under normal conditions. We prospectively investigated the uptake of ¹⁸F FDG and ¹¹C MET PET in patients with craniopharyngioma prior to proton therapy.

Methods

Ten patients newly diagnosed with craniopharyngioma underwent PET imaging using ¹⁸F FDG and ¹¹C MET. PET and MRI studies were registered to help identify tumor volume. Measurements of maximum standardized uptake value (SUV_max) were taken of the tumor and compared with noninvolved left frontal background white matter using a paired t-test. Uptake was graded using a 4-point scale.

Results

Median patient age was 9 years (range 5–19). Seven patients were diagnosed by pathology, 1 by cyst fluid aspiration, and 2 by neuroimaging. Median FDG SUV_max for tumor and background were 2.65 and 3.2, respectively. Median MET SUV_max for tumor and background were 2.2 and 1, respectively. There was a significant difference between MET tumor SUV_max and MET background SUV_max (P = .0001). The difference between FDG tumor SUV_max and FDG background SUV_max was not significant (P = .3672).

Conclusion

¹¹C MET PET uptake is significantly greater within the tumor compared with noninvolved background white matter, making it more useful than FDG PET in identifying active tumor in patients with craniopharyngioma. Future work will focus on using ¹¹C MET PET to discriminate between active and inactive tumor after irradiation.     

Preoperative [11C]methionine PET to personalize treatment decisions in patients with lower-grade gliomas

BackgroundPET with radiolabeled amino acids is used in the preoperative evaluation of patients with glial neoplasms. This study aimed to assess the role of [¹¹C]methionine (MET) PET in assessing molecular features, tumor extent, and prognosis in newly diagnosed lower-grade gliomas (LGGs) surgically treated.MethodsOne hundred and fifty-three patients with a new diagnosis of grade 2/3 glioma who underwent surgery at our Institution and were imaged preoperatively using [¹¹C]MET PET/CT were retrospectively included. [¹¹C]MET PET images were qualitatively and semi-quantitatively analyzed using tumor-to-background ratio (TBR). Progression-free survival (PFS) rates were estimated using the Kaplan-Meier method and Cox proportional-hazards regression was used to test the association of clinicopathological and imaging data to PFS.ResultsOverall, 111 lesions (73%) were positive, while thirty-two (21%) and ten (6%) were isometabolic and hypometabolic at [¹¹C]MET PET, respectively. [¹¹C]MET uptake was more common in oligodendrogliomas than IDH-mutant astrocytomas (87% vs 50% of cases, respectively). Among [¹¹C]MET-positive gliomas, grade 3 oligodendrogliomas had the highest median TBR_max (3.22). In 25% of patients, PET helped to better delineate tumor margins compared to MRI only. In IDH-mutant astrocytomas, higher TBR_max values at [¹¹C]MET PET were independent predictors of shorter PFS.ConclusionsThis work highlights the role of preoperative [¹¹C]MET PET in estimating the type of suspected LGGs, assessing tumor extent, and predicting biological behavior and prognosis of histologically confirmed LGGs. Our findings support the implementation of [¹¹C]MET PET in routine clinical practice to better manage these neoplasms.     

Metabolic characterization of childhood brain tumors: comparison of 18F-fluorodeoxyglucose and 11C-methionine positron emission tomography

BACKGROUND: Positron emission tomography (PET) scans of primary brain tumors were performed in pediatric patients to examine whether metabolic characteristics could be used as an index of clinical aggressiveness. METHODS: Twenty-seven pediatric patients with untreated primary central nervous system neoplasms were studied with PET scans using 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG) and/or L-[methyl-(11)C] methionine (MET). Metabolic characteristics as assessed with FDG and MET standardized uptake values (SUV) and SUV-to-normal brain ratios were compared with histopathology and selected histochemical features such as proliferation activity (Ki-67(MIB-1)) and apoptotic, vascular, and cell density indices. The median followup time was 43 months. RESULTS: The accumulation of both FDG and MET was significantly higher in high-grade than in low-grade tumors, but a considerable overlap was found. The accumulation of both tracers was associated positively with age. High-grade tumors showed higher proliferative activity and vascularity than the low-grade tumors. In univariate analysis, FDG-PET, MET-PET, and apoptotic index were independent predictors of event-free survival. CONCLUSION: We found that both FDG and MET uptake in pediatric brain tumors are associated with malignancy grade. However, no clear limits of SUVs and SUV-to-normal brain ratios can be set between low-grade and high-grade tumors, which makes the assessment of malignancy grade using metabolic imaging with PET scan difficult in individual cases. Although FDG-PET and MET-PET do not compensate for histopathologic evaluation, they may give valuable additional information especially if invasive procedures to obtain histopathologic samples are not feasible.     

Evaluation of thoracic tumors with 18F‐FMT and 18F‐FDG PET‐CT: A clinicopathological study

L‐[3‐¹⁸F]‐α‐methyltyrosine (¹⁸F‐FMT) is an aminoacid tracer for positron emission tomography (PET). The aim of this study was to determine whether PET‐CT with ¹⁸F‐FMT provides additional information for the preoperative diagnostic workup as compared with ¹⁸F‐FDG PET. PET‐CT studies with ¹⁸F‐FMT and ¹⁸F‐FDG were performed as a part of the preoperative workup in 36 patients with histologically confirmed bronchial carcinoma, 6 patients with benign lesions and a patient with atypical carcinoid. Expression of L‐type amino acid transporter 1 (LAT1), CD98, Ki‐67 labeling index, VEGF, CD31 and CD34 of the resected tumors were analyzed by immunohistochemical staining, and correlated with the uptake of PET tracers. For the detection of pulmonary malignant tumors, ¹⁸F‐FMT PET exhibited a sensitivity of 84% whereas the sensitivity for ¹⁸F‐FDG PET was 89% (p = 0.736). ¹⁸F‐FMT PET‐CT and ¹⁸F‐FDG PET‐CT agreed with pathological staging in 85 and 68%, respectively (p = 0.151). ¹⁸F‐FMT uptake was closely correlated with LAT1, CD98, cell proliferation and angiogenesis. The specificity of ¹⁸F‐FMT PET for diagnosing thoracic tumors was higher than that of ¹⁸F‐FDG PET. Our results suggest that coexpression of LAT1 and CD98 in addition to cell proliferation and angiogenesis is relavant for the progression and metastasis of lung cancer. © 2008 Wiley‐Liss, Inc.     

Characteristics of time-activity curves obtained from dynamic 11C-methionine PET in common primary brain tumors

Purpose

The aim of this study was to assess whether dynamic PET with ¹¹C-methionine (MET) (MET-PET) is useful in the diagnosis of brain tumors.

Methods

One hundred sixty patients with brain tumors (139 gliomas, 9 meningiomas, 4 hemangioblastomas and 8 primary central nervous system lymphomas [PCNSL]) underwent dynamic MET-PET with a 3-dimensional acquisition mode, and the maximum tumor MET-standardized uptake value (MET-SUV) was measured consecutively to construct a time-activity curve (TAC). Furthermore, receiver operating characteristic (ROC) curves were generated from the time-to-peak (TTP) and the slope of the curve in the late phase (SLOPE).

Results

The TAC patterns of MET-SUVs (MET-TACs) could be divided into four characteristic types when MET dynamics were analyzed by dividing the MET-TAC into three phases. MET-SUVs were significantly higher in early and late phases in glioblastoma compared to anaplastic astrocytoma, diffuse astrocytoma and the normal frontal cortex (P??1 for the differentiation of tumors that included an oligodendroglial component from astrocytic tumors, the diagnostic accuracy was 74.2% sensitivity and 64.9% specificity. The area under the ROC curve was 0.731.

Conclusions

The results of this study show that quantification of the MET-TAC for each brain tumor identified by a dynamic MET-PET study could be helpful in the non-invasive discrimination of brain tumor subtypes, in particular gliomas.

     

Prediction of Pathology and Survival by FDG PET in Gliomas

Objectives: 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. Methods: 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 white matter; 2 = uptake greater than normal white matter and less than gray matter; 3 = uptake equal to or greater than gray mater. The measure of association of lambda was used to measure the strength of predictive ability of FDG PET for pathological grading of the gliomas. The Cox proportional hazards regression model was used to assess the significance of grade of uptake on survival. Results: A total of 331 patients were analyzed of which 137 had a PET scan prior to histological diagnosis and therapeutic intervention (mean age = 46.5years; M:F = 1.7:1). Eighty six percent (143/166) of the patients with low uptake (metabolic scores 0,1) had low-grade gliomas (grade I,II) and 14% (23/166) high-grade gliomas (grade III,IV) on histologic examination. Ninety four percent (154/165) of the patients with high uptake (metabolic scores 2,3) on PET had high-grade gliomas and 7% (11/165) had low-grade gliomas on histologic examination. The grade of uptake had increasing significance on survival as the level increased from 'low' to 'high' (P = 0.0009). Ninety four percent (156/166) of the patients with low uptake survived for >1 year (median survival of 28 months) and 19% survived for >5 years. Only 29% (48/165) of patients with high uptake survived for >1 year, (median survival of 11 months) and none survived for >5 years. Irrespective of when the scan showed a high uptake of FDG, before or after intervention, the prognosis following that scan was poor. Conclusions: Our observations confirm the utility of FDG PET as a prognostic tool for the histological grading and survival in patients with gliomas and appears to more than complement pathological grading.     

Phenotype versus genotype in gliomas displaying inter- or intratumoral histological heterogeneity.

PURPOSE: Molecular classification of gliomas is becoming increasingly important clinically as an adjunct to histopathological diagnosis. Whereas histological heterogeneity of gliomas is well recognized, less is known of the relationship between histological heterogeneity and genetic alterations. Our objective was to investigate the relationship between genotype and phenotype for markers of potential clinical utility in histologically heterogeneous gliomas. EXPERIMENTAL DESIGN: We have used laser capture microdissection to sample the various histological phenotypes present in 42 tumors from 25 glioma cases with either inter- or intratumoral histological heterogeneity, and multiple simultaneous PCR amplification of microsatellite markers and capillary electrophoresis to determine allelic imbalance in chromosomes 1p, 19q, 17p, 10p, and 10q. RESULTS: Loss of 1p36 and 19q13 was seen only in oligodendroglial histology in 7 of 13 oligodendrogliomas. 17p13 loss was found in 14 of 41 tumors in astrocytic, oligoastrocytic, oligodendroglial, and glioblastomatous histologies. Chromosome 10 loss was seen in all of the high-grade histologies in 7 of 7 glioblastomas with an oligodendroglial component and in 1 of 5 low-grade oligodendroglial regions present within high-grade tumors. Seven tumors from 5 cases had no detectable losses of any markers investigated. In 13 tumors with intratumoral heterogeneity, identical genetic losses were present in all areas of histological differentiation. Additional losses were seen in some but not all of the histologies within 2 tumors and were associated with progression in 3 cases. CONCLUSIONS: The gliomas in this study were more homogeneous in their genotype than their histological phenotype with regions of differing histological subtype indistinguishable by the genetic markers investigated, supporting a monoclonal origin of these tumors.     

Comparison of magnetic resonance spectroscopy and positron emission tomography in detection of tumor recurrence in posttreatment of glioma: A diagnostic meta‐analysis

It is important to distinguish between tumor recurrence and treatment effects in posttreatment patients with high‐grade gliomas. Several imaging modalities have been reported in differentiating between tumor recurrence and treatment effects. However, there were no consistent conclusions between different studies. We performed a meta‐analysis of 23 studies that compared the diagnostic values of fluorine‐18‐fluorodeoxyglucose (¹⁸F‐FDG) and ¹¹C‐methionine (¹¹C‐MET) PET (positron emission tomography) or PET/CT (computed tomography) and magnetic resonance spectroscopy (MRS) in predicting tumor recurrence of gliomas. The pooled estimated sensitivity, specificity, positive likelihood ratios, negative likelihood ratios and summary receiver operating characteristic curves of ¹⁸F‐FDG and ¹¹C‐MET PET or PET/CT and MRS in detecting tumor recurrence were calculated. In conclusion, MRS is highly sensitive in the detection of tumor recurrence in glioma.¹⁸F‐FDG PET or PET/CT is highly specific in recurrence diagnosis. ¹¹C‐MET does not have noticeable advantage over ¹⁸F‐FDG. The current evidence shows no statistical difference between MRS and PET on the accuracy.     

FDG transport and phosphorylation in human gliomas measured with dynamic PET

Twenty-six patients with gliomas of WHO-grades two to four were examined with dynamic positron emission tomography (PET) and ¹⁸F-2-fluoro-2-deoxy-D-glucose (FDG). FDG rate constants and derived glucose metabolic rates (MR_dyn) were determined in solid tumor tissue and in tumor-free brain tissue. In addition, glucose metabolism was also calculated from single scans recorded 30 to 40 min after injection (MR_stat).All three rate constants, K₁, k₂, and k₃, were significantly correlated with MR_dyn in tumor-free brain. In contrast, in gliomas only k₃ was significantly correlated with MR_dyn. The ratio of k₃ in tumors to k₃ in tumor-free brain was also significantly related to histological tumor grade. The results indicate that FDG uptake in brain tumors is governed by FDG phosphorylation and is rather independent from the variation of FDG transport. A comparison between glucose metabolic rates calculated by an autoradiographic approach (MR_stat) with the calculation based on individually fitted rate constants (MR_dyn) revealed a very close correlation in spite of a moderate systematic difference in absolute values.     

Association of 82 Rubidium and 11C-methionine uptake in brain tumors measured by positron emission tomography

Summary Positron emission tomography (PET) studies have indicated that alteration of active transport contributes to increased net amino acid accumulation into human brain tumors. We compared the uptake of ¹¹C-methionine (MET) and the K⁺ analog ⁸²Rubidium (RUB) in 30 patients suffering from various brain tumors using PET. MET and RUB accumulated rapidly in tumor tissue and remained on average at a stable level thereafter from which normalized uptake values were calculated (tissue radioactivity over injected radioactivity × body weight (NU)). K1 (RUB) and K1, k2, 0 (MET) were also estimated using non-linear rate constant fitting in 17/30 patients. NU and K1 values were significantly correlated for MET (Spearman Rank p < 0.005) and RUB (p < 0.001). NU and K1 values for MET and RUB were higher in meningiomas compared to gliomas and were significantly correlated for the whole spectrum of tumors (p < 0.001). When meningiomas were excluded, the correlation was maintained. K3 values for MET (metabolic rate) in tumors were in the range of normal brain. No correlation between RUB and MET was found for normal brain. With increasing RUB uptake, the ratio of NU MET over NU RUB approached the value of 1.0. These results suggest that apart from active transport, also passive diffusion across the blood-brain barrier (BBB) may account for MET uptake from blood into tumor tissue. This probably limits the use of MET in the differential diagnosis of brain lesions where BBB disruption is present.     

A surgical strategy using a fusion image constructed from 11C-methionine PET, 18F-FDG-PET and MRI for glioma with no or minimum contrast enhancement

The objective of this study was to investigate the distribution of 11C-methionine (MET) and F-18 fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) imaging and the hyperintense area in T2 weighted imaging (T2WI) in glioma with no or poor gadolinium enhancement in magnetic resonance imaging (GdMRI). Cases were also analyzed pathologically. We prospectively investigated 16 patients with non- or minimally enhancing (<?10% volume) glioma. All patients underwent MET-PET and FDG-PET scans preoperatively. After delineating the tumor based on MET uptake, integrated 3D images from FDG-PET and MRI (GdMRI, T2WI or FLAIR) were generated and the final resection plane was planned. This resection plane was determined intraoperatively using the navigation-guided fencepost method. The delineation obtained by MET-PET imaging was larger than that with GdMRI in all cases with an enhanced effect. In contrast, the T2WI-abnormal signal area (T2WI+) tended to be larger than the MET uptake area (MET+). Tumor resection was >?95% in the non-eloquent area in 4/5 cases (80%), whereas 10 of 11 cases (90.9%) had partial resection in the eloquent area. In a case including the language area, 92% resection was achieved based on the MET-uptake area, in contrast to T2WI-based partial resection (65%), because the T2WI+/MET? area defined the language area. Pathological findings showed that the T2WI+/MET+ area is glioma, whereas 6 of 9 T2WI+/MET? lesions included normal tissues. Tissue from T2W1+/MET+/FDG+/GdMRI+ lesions gave an accurate diagnosis of grade in six cases. Non- or minimally enhancing gliomas were classified as having a MET uptake area that totally or partially overlapped with the T2WI hyperintense area. Resection planning with or without a metabolically active area in non- or minimally enhancing gliomas may be useful for accurate diagnosis, malignancy grading, and particularly for eloquent area although further study is needed to analyze the T2WI+/MET? area.     

Imaging 18F-fluorodeoxy glucose/11C-methionine uptake decoupling for identification of tumor cell infiltration in peritumoral brain edema

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.     

Evaluation of brain tumor metabolism with [11C]choline PET and 1H-MRS

Background: The signal of choline containing compounds (Cho) in proton magnetic resonance spectroscopy (¹H-MRS) is elevated in brain tumors. [¹¹C]choline uptake as assessed using positron emission tomography (PET) has also been suggested to be higher in brain tumors than in the normal brain. We examined whether quantitative analysis of choline accumulation and content using these two novel techniques would be helpful in non-invasive, preoperative evaluation of suspected brain tumors and tumor malignancy grade. Methods: 12 patients with suspected brain tumor were studied using [¹¹C]choline PET, gadolinium enhanced 3-D magnetic resonance imaging and ¹H-MRS prior to diagnostic biopsy or resection. Eleven normal subjects served as control subjects for ¹H-MRS. Results: The concentrations of Cho and myoinositol (mI) were higher and the concentration of N-acetyl signal/group (NA) lower in brain tumors than in the corresponding regions of the normal brain. There were no significant differences in metabolite concentrations between low- and high-grade gliomas. In non-tumorous lesions Cho concentrations were lower and NA concentrations higher than in any of the gliomas. Enormously increased lipid peak differentiated lymphomas from all other lesions. The uptake of [¹¹C]choline at PET did not differ between low- and high-grade gliomas. The association between Cho concentration determined in ¹H-MRS and [¹¹C]choline uptake measured with PET was not significant. Conclusion: Both ¹H-MRS and [¹¹C]choline PET can be used to estimate proliferative activity of human brain tumors. These methods seem to be helpful in differential diagnosis between lymphomas, non-tumorous lesions and gliomas but are not superior to histopathological methods in estimation of tumor malignancy grade.     

Evaluation of <Superscript>11</Superscript>C-methionine PET as a surrogate endpoint after treatment of grade 2 gliomas

The aim of the present study was to assess the usefulness of positron emission tomography (PET) as a surrogate endpoint by analysing the uptake variability of ¹¹C-methionine (MET) in follow-up scans.A total of 96 PET MET scans were re-evaluated in 32 patients with histologically confirmed supratentorial grade 2 gliomas.In untreated patients, all follow-up PET scans showed an increased tumour volume after median 68 weeks, but only 46% of cases had an increased hot spot uptake. An improved outcome was observed in patients with stable hot spot uptake per se (P=0.07) and in combinations with minor increase in tumour volume (P=0.02). After conventional therapy, 52% of PET scans showed a reduced hot spot uptake the first year and 43% were reduced after more than a year. Successful MET decline after therapy did not correlate with outcome.PET MET may be a promising surrogate endpoint after treatment of grade 2 gliomas. Evaluation of both hot spot activity and uptake volume on PET may strengthen the association with clinical outcome.     

Correlation of F-18-fluoro-ethyl-tyrosin uptake with vascular and cell density in non-contrast-enhancing gliomas

Objective Even without contrast enhancement on MRI scans gliomas can show histological features of anaplasia. These tumors are heterogeneous regarding anaplastic and non-anaplastic areas. Increased amino acid uptake was shown to be associated with dismal prognosis in gliomas. We investigated histological correlates of tumor grading in biopsies obtained from regions with maximum amino acid uptake revealed by F-18-fluoro-ethyl-tyrosin positron emission tomography (FET-PET). Methods We included 22 patients with non-contrast enhancing lesions on MRI scans. PET was performed 10 min after FET injection, and the area of maximum FET uptake was chosen as the biopsy target. In 13 patients neuronavigated biopsies were obtained during tumor resection. Nine patients had a stereotactic biopsy. The ratio of maximum standardized uptake value (SUV) to background was calculated. Histological specimens were classified and graded according to world health organization (WHO) criteria. We investigated cell and vascular density, mitotic activity, proliferation index, microvascular proliferation, nuclear pleomorphism, necrosis and immunoreactivity of LAT1 (SLC7A5), an amino acid transporter with prognostic impact in gliomas. Results 12 of the 22 non-contrast enhancing gliomas corresponded to anaplastic astrocytomas WHO grade III. Vascular and cellular density was correlated highly to the SUV ratio (P = 0.0015 and P = 0.0021, respectively), but with no nuclear pleomorphism, mitotic activity, Mib-1 immunoreactivity, or microvascular proliferation. Thus, no correlation was found between FET uptake and tumor grade. Conclusion FET-PET correlates with vascular and cell density in non-contrast enhancing gliomas. Although tumor grade cannot be predicted, clinical use of FET PET as an indicator for neovascularization should be addressed in future studies. Florian Stockhammer and Michail Plotkin contributed equally to this work. Christian Woiciechowsky and Frank van Landeghem contributed equally to this work.     

Potential use of prostate specific membrane antigen (PSMA) for detecting the tumor neovasculature of brain tumors by PET imaging with <Superscript>89</Superscript>Zr-Df-IAB2M anti-PSMA minibody

Tumor angiogenesis has attracted increasing attention because of its potential as a valuable marker in the differential diagnosis of brain tumors as well as a novel therapeutic target. Prostate-specific membrane antigen (PSMA) is expressed by the neovasculature endothelium of some tumors, with little to no expression by the tumor cells or normal vasculature endothelium. The aim of this study was to investigate the potential of PSMA for the evaluation of the tumor neovasculature of various brain tumors and the possibility of detecting PSMA expression in brain tumors using PET imaging with ⁸⁹Zr-Df-IAB2M (anti-PSMA minibody). Eighty-three tissue specimens including gliomas, metastatic brain tumors, primary central nervous system lymphomas (PCNSL), or radiation necroses were analyzed by immunohistochemical staining with PSMA antibody. ⁸⁹Zr-Df-IAB2M PET scans were performed in three patients with recurrent high-grade gliomas or metastatic brain tumor. PSMA was highly expressed in the vascular endothelium of high-grade glioma and metastatic brain tumor, whereas PSMA was poorly expressed in the vascular endothelium of PCNSL and radiation necrosis. PSMA expression in high-grade gliomas and a metastatic brain tumor was clearly visualized by PET imaging with ⁸⁹Zr-Df-IAB2M. Furthermore, a trend toward a positive correlation between the degree of ⁸⁹Zr-Df-IAB2M uptake and PSMA expression levels in tumor specimens was observed. PET imaging of PSMA using ⁸⁹Zr-Df-IAB2M may have potential value in the differential diagnosis of high-grade glioma from PCNSL or radiation necrosis as well as in the prediction of treatment efficacy and assessment of treatment response to bevacizumab therapy for high-grade glioma.     

Tracer transport and metabolism in a patient with juvenile pilocytic astrocytoma. A PET study

We studied a patient with juvenile pilocytic astrocytoma (JPA) using positron emission tomography (PET), ¹⁸ F-fluorodeoxyglucose (FDG),¹¹ C-methionine (MET), and ⁸²Rubidium (RUB). Non-linear fitting and multiple time graphical plotting of the dynamic PET data revealed values for tumor plasma volume, blood-brain barrier transport rate constants and tracer distribution volume in the range of glioblastomas and meningiomas, or higher. Likewise, the steady-state accumulation of MET and FDG was increased. With regard to the known vascular composition of JPA, our data suggest that increased transport and distribution considerably contribute to the high net tracer uptake observed in this tumor.     

High and Low Grade Oligodendrogliomas (ODG): Correlation of Amino-Acid and Glucose Uptakes Using PET and Histological Classifications

Classification and treatment strategy of oligodendrogliomas (ODG) remain controversial. Imaging relies essentially on contrast enhancement using CT or MRI. The aim of our study was to use positron emission tomography (PET) using [18F]-flurodeoxyglucose (FDG) and [11C]-L-methyl-methionine (MET) to evaluate metabolic characteristics of ODG. We studied 19 patients with proven ODG, comparing standardized uptake values (SUV) and maximal tumor/contralateral normal tissues ratios (T/N). Imaging findings were compared with WHO, Smith and Daumas-Duport classifications. Uptake of FDG was decreased only in 8 patients, independently of grading, while MET uptake was always increased. MET uptake was significantly higher for high grade tumors grouped according to Smith or Daumas-Duport classifications, while no significant difference in MET uptake was found when using WHO classification. A different correlation was found between FDG and MET uptakes in normal tissues and high grade tumors. A trend for improved progression free survival was found for tumors that lacked contrast enhancement on MRI or those showing low FDG or MET uptake. In conclusion, MET appeared more sensitive than FDG to detect proliferation in ODG. The preferential protein metabolism, already noticeable for low-grade tumor, correlated with glucose metabolism and helped to separate, in vivo, high and low grade tumors.     

Clinical characteristics of meningiomas assessed by 11C-methionine and 18F-fluorodeoxyglucose positron-emission tomography

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 < 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.