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Objective: 11C-Methionine positron emission tomography (MET-PET) is used for stereotactic radiotherapy planning in meningioma patients. The role of MET-PET during subsequent follow-up (FU) is unclear. We analyzed the uptake of 11C-Methionine before and after stereotactic radiotherapy (SRT) in patients with a complex meningioma and investigated if there was a difference between patients with progressive disease (PD) and stable disease (SD) during FU. Methods: This retrospective study investigates 62 MET-PETs in 29 complex meningioma patients. Standardized uptake value (SUV)max and SUVpeak tumor-to-normal ratios (T/N-ratios) were calculated, comparing the tumor region with both the mirroring intracranial area and the right frontal gray matter. The difference in 11C-Methionine uptake pre- and post-SRT was analyzed, as well as the change in uptake between PD or SD. Results: Median (IQR) FU duration was 67 months (50.5–91.0). The uptake of 11C-Methionine in meningiomas remained increased after SRT. Neither a statistically significant difference between MET-PETs before and after SRT was encountered, nor a significant difference in one of the four T/N-ratios between patients with SD versus PD with median (IQR) SUVmax T/NR front 2.65 (2.13–3.68) vs 2.97 (1.55–3.54) [p = 0.66]; SUVmax T/Nmirror 2.92 (2.19–3.71) vs 2.95 (1.74–3.60) [p = 0.61]; SUVpeak T/NR front 2.35 (1.64–3.40) vs 2.25 (1.44–3.74) [p = 0.80]; SUVpeak T/Nmirror 2.38 (1.91–3.36) vs 2.35 (1.56–3.72) [p = 0.95]. Conclusions: Our data do not support use of MET-PET during FU of complex intracranial meningiomas after SRT. MET-PET could not differentiate between progressive or stable disease. [ABSTRACT FROM AUTHOR]

Introduction: Amino-acid positron emission tomography (PET) is a validated metabolic imaging approach for the diagnostic work-up of gliomas. This study aimed to evaluate sex-specific radiomic characteristics of L-[S-methyl-11Cmethionine (MET)-PET images of glioma patients in consideration of the prognostically relevant biomarker isocitrate dehydrogenase (IDH) mutation status. Methods: MET-PET of 35 astrocytic gliomas (13 females, mean age 41 ± 13 yrs. and 22 males, mean age 46 ± 17 yrs.) and known IDH mutation status were included. All patients underwent radiomic analysis following imaging biomarker standardization initiative (IBSI)-conform guidelines both from standardized uptake value (SUV) and tumor-to-background ratio (TBR) PET values. Aligned Monte Carlo (MC) 100-fold split was utilized for SUV and TBR dataset pairs for both sex and IDH-specific analysis. Borderline and outlier scores were calculated for both sex and IDHspecificMC folds. Feature ranking was performed by R-squared ranking and Mann- Whitney U-test together with Bonferroni correction. Correlation of SUV and TBR radiomics in relation to IDH mutational status in male and female patients were also investigated. Results: There were no significant features in either SUV or TBR radiomics to distinguish female and male patients. In contrast, intensity histogram coefficient of variation (ih.cov) and intensity skewness (stat.skew) were identified as significant to predict IDH +/-. In addition, IDH+ females had significant ih.cov deviation (0.031) and mean stat.skew (-0.327) differences compared to IDH+ male patients (0.068 and -0.123, respectively) with two-times higher standard deviations of the normal brain background MET uptake as well. Discussion: We demonstrated that female and male glioma patients have significantly different radiomic profiles in MET PET imaging data. Future IDH prediction models shall not be built on mixed female-male cohorts, but shall rely on sex-specific cohorts and radiomic imaging biomarkers. [ABSTRACT FROM AUTHOR]

IntroductionAmino-acid positron emission tomography (PET) is a validated metabolic imaging approach for the diagnostic work-up of gliomas. This study aimed to evaluate sex-specific radiomic characteristics of L-[S-methyl-11Cmethionine (MET)-PET images of glioma patients in consideration of the prognostically relevant biomarker isocitrate dehydrogenase (IDH) mutation status.MethodsMET-PET of 35 astrocytic gliomas (13 females, mean age 41 ± 13 yrs. and 22 males, mean age 46 ± 17 yrs.) and known IDH mutation status were included. All patients underwent radiomic analysis following imaging biomarker standardization initiative (IBSI)-conform guidelines both from standardized uptake value (SUV) and tumor-to-background ratio (TBR) PET values. Aligned Monte Carlo (MC) 100-fold split was utilized for SUV and TBR dataset pairs for both sex and IDH-specific analysis. Borderline and outlier scores were calculated for both sex and IDH-specific MC folds. Feature ranking was performed by R-squared ranking and Mann-Whitney U-test together with Bonferroni correction. Correlation of SUV and TBR radiomics in relation to IDH mutational status in male and female patients were also investigated.ResultsThere were no significant features in either SUV or TBR radiomics to distinguish female and male patients. In contrast, intensity histogram coefficient of variation (ih.cov) and intensity skewness (stat.skew) were identified as significant to predict IDH +/-. In addition, IDH+ females had significant ih.cov deviation (0.031) and mean stat.skew (-0.327) differences compared to IDH+ male patients (0.068 and -0.123, respectively) with two-times higher standard deviations of the normal brain background MET uptake as well.DiscussionWe demonstrated that female and male glioma patients have significantly different radiomic profiles in MET PET imaging data. Future IDH prediction models shall not be built on mixed female-male cohorts, but shall rely on sex-specific cohorts and radiomic imaging biomarkers.

Simple Summary: In malignant brain tumor surgery, precise identification of the tumor is essential. 5-Aminolevulinic acid (5-ALA) labels tumor cells with red fluorescence to facilitate tumor resection. On the other hand, the nuclear medicine imaging technique, positron emission tomography with 11C-methionine (MET-PET), can delineate tumors precisely but is not widely available. This study aimed to determine the correlation between intraoperative 5-ALA-induced fluorescence and preoperative MET-PET signals of gliomas. We quantitatively measured the fluorescence intensity from tumor samples and calculated the MET-PET uptake by the tumor. Our study showed that strong tumor fluorescence correlated with high MET-PET uptake and cellular proliferation. Our findings might be valuable to rapidly provide information on tumor biology at the time of surgery in circumstances where MET-PET is inaccessible. Background: 5-Aminolevulinic acid (5-ALA) is widely employed to assist fluorescence-guided surgery for malignant brain tumors. Positron emission tomography with 11C-methionine (MET-PET) represents the activity of brain tumors with precise boundaries but is not readily available. We hypothesized that quantitative 5-ALA-induced fluorescence intensity might correlate with MET-PET uptake in gliomas. Methods: Adult patients with supratentorial astrocytic gliomas who underwent preoperative MET-PET and surgical tumor resection using 5-ALA were enrolled in this prospective study. The regional tumor uptake of MET-PET was expressed as the ratio of standardized uptake volume max to that of the normal contralateral frontal lobe. A spectrometric fluorescence detection system measured tumor specimens' ex vivo fluorescence intensity at 635 nm. Ki-67 index and IDH mutation status were assessed by histopathological analysis. Use of an antiepileptic drug (AED) and contrast enhancement pattern on MRI were also investigated. Results: Thirty-two patients, mostly with Glioblastoma IDH wild type (46.9%) and anaplastic astrocytoma IDH mutant (21.9%), were analyzed. When the fluorescence intensity was ranked into four groups, the strongest fluorescence group exhibited the highest mean MET-PET uptake and Ki-67 index values. When rearranged into fluorescence Visible or Non-visible groups, the Visible group had significantly higher MET-PET uptake and Ki-67 index compared to the Non-visible group. Contrast enhancement on MRI and IDH wild type tumors were more frequent among the Visible group. AED use did not correlate with 5-ALA-induced fluorescence intensity. Conclusions: In astrocytic glioma surgery, visible 5-ALA-induced fluorescence correlated with high MET-PET uptake, along with a high Ki-67 index. [ABSTRACT FROM AUTHOR]

The aims of the present study were to compare the longitudinal changes of glioblastoma multiforme after radiotherapy (RT) between 11C-methionine positron emission tomography (MET-PET) and gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) and to clarify whether these changes were predictive of survival. We included 30 patients, who had undergone MET-PET and Gd-MRI before and every 3 months after RT. The lesion/normal brain uptake (L/N) ratio and contrast-enhancing lesion volume were examined. The L/N ratio was decreased until 9 months after RT with significance until 3 months. The contrast-enhancing lesion volume was decreased until 3 months and thereafter increased until 9 months with significance. The variation rates of the L/N ratio between pre-RT and 3 months differentiated survival of >23 months from ≤23 months. A dissociation could exist in the longitudinal changes of GBM after RT between MET-PET and Gd-MRI. The variation rate of the L/N ratio could be related to survival. [ABSTRACT FROM AUTHOR]

Positron emission tomography and multiparametric MRI provide crucial information concerning tumor extent and normal tissue anatomy. Moreover, they are able to visualize biological characteristics of the tumor, which can be considered in the radiation treatment planning and monitoring. In this review we discuss the impact of biological imaging positron emission tomography and multiparametric MRI for radiation oncology, based on the data of the literature and on the experience of our own institution in this field. [ABSTRACT FROM AUTHOR]

Objective: The tumour-to-normal ratio (T/N) is a representative index reflecting brain tumour activity by 18F-fluorodeoxyglucose (FDG) and 11C-methionine (MET) PET. We proposed a new automated method of calculating the normal reference value (N-value) for use as the denomination of T/N. This method uses voxel-based analysis of FDG- and MET-PET images. We compared the results of this method with those of the standard region-of-interest (ROI) method.Methods: Data sets were obtained from 32 patients with newly diagnosed glioma and 13 patients with recurrent brain tumour. Our methods were as follows: (1) FDG-PET and MET-PET images were co-registered. (2) The areas where the FDG uptake was higher than a set threshold were selected. (3) For the corresponding areas of MET-PET images, mode and mean voxel values were calculated as tentative MET N-values. (4) Applying the same coordinates to FDG-PET, the voxel values were averaged and used as tentative FDG N-values. (5) The threshold of FDG-PET and whether to use the mode or the mean voxel values were computationally optimized using learning data sets. (6) Applying the optimal threshold and either the mode or mean, N-values of FDG and MET were finally determined.Results: N-values determined by our automated method showed excellent agreement with those determined by a manual ROI method (ICC(2,1) > 0.78). These values were significantly correlated with mean manual N-values (p < 0.001).Conclusions: Our new method shows sufficiently good agreement with the standard method and can provide a more objective metabolic index. [ABSTRACT FROM AUTHOR]

We assessed the prognostic utility of C-Methionine positron emission tomography (MET-PET) in pediatric high-grade glioma (HGG). Thirty-one children had 62 MET-PET studies. Segmented tumor volumes from co-registered magnetic resonance studies were assessed for concordance with MET-PET uptake using Boolean operations. The tumor volume at diagnosis and treatment failure was assessed relative to MET-PET avid volume. The prognostic impact of MET-PET-delineated non-contrast enhancing tumor (NCET) was assessed. NCET was defined as the region of tumor defined by defined by FLAIR which did not enhance but showed MET-PET avidity. MET-PET concordance varied according to magnetic resonance sequence. MET-PET rarely added to the tumor volume in most cases. The volume of MET-PET with standardized uptake value >3.0 was differentially distributed at diagnosis, post treatment, and at recurrence. The initial MET-PET region overlapped with recurrent tumor in 90% of the cases. When the proportion of tumor which was NCET was >10%, an earlier time to progression (5.8 months; 95% CI, 1-8.2 vs. 10.5 months; 95% CI, 0.9-NR; p = 0.035) was noted. MET-PET delineates regions at increased risk for recurrence and may improve the definition of failure, prognostic assessment, and target definition for radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the impact of fluid-attenuated-inversion-recovery MRI (FLAIR/MRI) and Carbon-11-labeled-methionine PET (11C-MET-PET) on high grade glioma (HGG) tumor volume delineation for radiotherapy planning. Material and methods Sixty-nine patients with HGG were evaluated. The clinical target volumes (CTV1, generated by adding a 10 mm margin to FLAIRMRI area, CTV2 by adding a 20 mm margin to enhanced T1MRI) and biological target volume (BTV) were delineated on pre-operative MRI images and 11CMETPET respectively. Results The overlap between CTV1 and CTV2 showed a low correlation between the two volumes with CTV1 not always fully included into the CTV2. In all cases the whole BTV was included into the CTV1, while in 35/69 patients (50%) part of BTV was outside the CTV2 despite larger margins were added. In all cases recurrences were within the CTV1 volume and in 19/38 (50%) partially outside the CTV2. In all patients relapse corresponded to the BTV area. Conclusions Our data suggest that the target volume definition using FLAIR–MRI is more adequate compared to enhanced T1MRI. 11C-METPET uptake could help identify microscopic residual areas. [ABSTRACT FROM AUTHOR]

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

Abstract: Background: The treatment of intracranial NGMGCTs is generally based on chemotherapy and radiotherapy. To avoid the potential of tumor recurrence, we normally have the residual mass lesion removed after adjuvant therapy. However, since 1988 we have treated 15 patients with NGMGCT and pathologically evaluated 12 such patients after adjuvant therapy by a new method we have developed and found viable tumor cells in 4 (33%) of 12 patients. Based on our experience, therefore, we feel we have been able to develop a reliable diagnostic tool for confirming the presence or absence of viable tumor cells in residual mass after adjuvant therapy for patients with NGMGCT. Case Description: We describe here 2 patients with NGMGCTs who underwent MET-PET. Patient 1 was an 11-year-old boy with immature teratoma. On gadolinium (Gd)-enhanced magnetic resonance imaging (MRI), a high-intensity area was found in his right cerebellar hemisphere and a high uptake in MET-PET was confirmed in the same region. We judged it as the recurrence of the tumor. Finally, he died and was autopsied. Patient 2 was a 16-year-old girl with an NGMGCT who received combined chemo- and radiotherapy that led to a reduction in the volume of the tumor. Her serum β-HCG and HCG levels also returned to the reference range. However, the mass did not disappear and another MRI scan disclosed a residual Gd-enhanced lesion. To assess whether there were residual viable tumor cells, MET-PET was performed, and it demonstrated no hyper-uptake region in the residual mass. We, therefore, did not surgically remove the mass and kept the patient under observation. There has not been any tumor recurrence in this patient for more than 2 years. Conclusion: In these 2 cases, the increased MET uptake was more specific of tumor tissue and more accurate than MR Gd enhancement. MET-PET may be a useful diagnostic tool for predicting viable tumor cells after adjuvant therapy in patients with NGMGCT, thus allowing further surgical intervention. [Copyright &y& Elsevier]

: Purpose(a) To implement a fully automatic method to integrate 11C-methionine positron emission tomography (MET-PET) data into stereotactic radiation treatment planning using the commercially available BrainLAB System, by means of CT/MET-PET image fusion. (b) To validate the fully automatic CT/MET-PET image fusion technique with respect to accuracy and robustness. (c) To give a short glance at the clinical consequences for patients with brain tumors.: Methods and materialsIn 12 patients with brain tumors (9 meningeomas, 3 gliomas), CT, MRI, and MET-PET were performed for stereotactic fractionated radiation treatment planning. The CT and MET-PET investigations were performed using a relocatable mask for head fixation. Fifteen external reference markers (5 on each lateral and 5 on the frontal localizer plate) that could be identified in CT and MET-PET were applied on the stereotactic localizer frame; the marker positions were exactly defined for both investigations. The MRI/CT fusion was done completely automatically. The CT/MET-PET fusion was performed using two different methods: The gold standard was the CT/PET fusion based on the reference markers, and the test method was the automatic, intensity-based CT/PET fusion, independent of the external markers. The markers visible on CT and transmission PET were matched using a point-to-line matching algorithm. To quantify the amount of misregistration, the two fusion methods were compared by calculating the mean value of deviation between corresponding points inside a cubic volume of interest of ≥512 cm3 defined within the cranial cavity. The gross tumor volume (CT/MRI) outlined on CT and T1-MRI with contrast medium was compared with the gross tumor volume (PET) defined in the reoriented MET-PET data sets. The clinical impact of MET-PET in tumor volume definition for stereotactic radiotherapy will be discussed.: ResultsThe fully automatic integration of MET-PET into stereotactic radiation treatment planning was successfully realized in all patients investigated. Mean deviation of the intensity-based automatic CT/PET fusion compared with the external marker–based gold standard was 2.4 mm; the standard deviation was 0.5. The algorithm’s robustness was evaluated, and the discrepancy of fusion results due to different initial image alignments was determined to be below 1 mm inside the test volume of interest. In patients with meningiomas and gliomas, MET-PET was shown to deliver additional information concerning tumor extension.: ConclusionThe precision of the automatic CT/PET image fusion was high. A mean deviation of 2.4 mm is acceptable, considering that it is approximately equal to the pixel size of the PET data sets. MET-PET improves target volume definition for stereotactic fractionated radiotherapy of meningiomas and gliomas. [Copyright &y& Elsevier]

Methionine (MET) dependence is a cancer-specific metabolic abnormality that is due to MET overuse for aberrant transmethylation reactions. [ 11 C]-MET is very useful for positron-emission tomography (PET) due to MET overuse in malignant tumors. Many benefits of MET-PET have been demonstrated. MET-PET can differentiate recurrent glioma and necrosis. [ 11 C]-MET-PET can also predict prognosis in gliomas better than [ 18 F]-FDG PET. [ 11 C]-MET-PET is better than MRI for predicting survival in low-grade glioma (LGG). MET-PET has greater specificity for detecting residual tumor after surgery than MRI.

Objective: [(11)C] methionine (MET) positron-emission tomography (PET) is a useful diagnostic and therapeutic tool in neuro-oncology. The aim of this study was to evaluate the relationship between MET uptake and the histopathological grade in both primary brain tumours and brain metastases. A secondary goal was to assess the relationship between MET uptake and patients' survival after surgery., Methods: We reviewed a consecutive series of 43 PET studies performed at our institution. Out of the 43 patients studied, 35 harboured primary brain tumours (3 grade I, 12 grade II, 7 grade III and 13 grade IV) and 8 patients had brain metastases. We measured the tumour/cortex ratio (T/C ratio) on each PET study and we investigated the correlations among the tracer uptake, tumour grade, tumour type, MRI parameters and outcome., Results: The mean T/C ratio was 1.8 ± 0.9 for benign lesions and low grade gliomas (grade I and II) and 2.7 ± 1 for high grade gliomas (grade III and IV). In brain metastases it was 2.5 ± 0.7, with a significant difference in MET uptake between low and high grades gliomas (P=0.03). There was no statistically significant difference among all different histologic types. We found that both contrast enhancement and perfusion studies correlate with MET uptake in brain tumours. Moreover, in Kaplan-Meier curves, the T/C ratio adversely affects long term survival in patients with brain tumours (P=0.01)., Conclusions: MET PET appears to be useful in diagnosis and evaluation of potential malignancy in brain tumours. MET uptake is also related with the overall survival in patients with brain tumours. Nevertheless, further studies are needed in order to define its possible clinical implications in identifying patients at high risk of tumour progression or resistance to therapy., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: Repeated chronic inflammation, such as under circumstances of ruptured Rathke's cleft cyst (RCC), is known as the fundamental basis of various pathological changes including neoplastic change, therefore to examine accurate incidence of pituitary adenomas is important for the preventive medicine., Materials and Methods: As a prospective study, patients were initially screened by the symptoms such as periodic headache and dizziness together with the abnormal findings such as seller floor bone defect on 3D-CT. Those screened patients who showed abnormal basal pituitary hormone values were additionally examined by several loading test and 3T magnetic resonance imaging (MRI) by three-dimensional reconstructions of Flair cube images. The presence of pituitary adenomas was evaluated by composite 3T MRI and (11)C methionine MET positron-emission tomography imaging. Immunohistochemical studies were employed for surgical biopsy specimens to demonstrate hormone production., Results: 308 cases of RCC were diagnosed by both radiologic and intraoperative findings. Pathological examination confirmed 111 pituitary adenomas in 106 patients with ruptured RCC, therefore the rate of coincidence was revealed 34%. In 78 patients with abnormalities of pituitary hormone secretion, MET uptake was observed in the pituitary gland and verified pituitary adenoma pathologically. In addition, 28 adenomas were verified without MET-PET study on pathological examination only, for a total of 106 cases., Conclusions: High coincidence (34%) of ruptured RCC and pituitary adenomas was demonstrated, which is a proof that ruptured RCC is contributed to a risk factor of pituitary adenoma., (Copyright © 2015 Elsevier B.V. All rights reserved.)