MET Positron Emission Tomography Research Articles

Comparative evaluation of 11C-methionine and 18F-fluorodeoxyglucose positron emission tomography for distinguishing between primary central nervous system lymphoma and isocitrate dehydrogenase-wildtype glioblastoma.

Distinguishing between primary central nervous system lymphoma (PCNSL) and isocitrate dehydrogenase (IDH)-wildtype glioblastoma is important for therapeutic decision-making. This study aimed to compare the performance of 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for distinguishing between these two major malignant brain tumors. We retrospectively conducted qualitative and semiquantitative analyses of pre-treatment MET and FDG PET/computed tomography (CT) images of 22 patients with PCNSL and 64 patients with IDH-wildtype glioblastoma. For semiquantitative analysis, we calculated the tumor-to-normal tissue (T/N) ratio by dividing the maximum standardized uptake value (SUV) for the tumor (T) by the average SUV for the normal tissue (N). For performance evaluation, we employed receiver operating characteristic curve analysis and calculated the areas under the curve (AUC) values. In the qualitative analysis, all PCNSLs and IDH-wildtype glioblastomas were MET-positive, while 95% and 84% of PCNSLs and IDH-wildtype glioblastomas, respectively, were FDG-positive. Eleven patients were excluded from the FDG PET/CT semiquantitative analysis because of hyperglycemia. There was no difference in MET T/N ratio between PCNSL and IDH-wildtype glioblastoma (p = 0.37). FDG T/N ratio was significantly higher in PCNSL than in IDH-wildtype glioblastoma (p < 0.001). The AUC value for distinguishing PCNSL from IDH-wildtype glioblastoma was significantly higher for the FDG T/N ratio (0.871) than for the MET T/N ratio (0.565) (p = 0.0027). MET PET could detect both PCNSL and IDH-wildtype glioblastoma, but unlike FDG PET, it could not distinguish between these two major malignant brain tumors.

Resection of positive tissue on methionine-PET is associated with improved survival in glioblastomas.

The volume of excised tumor in contrast-enhanced areas evaluated via magnetic resonance imaging is known to have a strong influence on the survival of patients with glioblastoma (GBM). In this study, we investigated the effect of tumor resection on the survival of patients with GBM in the 11 C-methionine (MET) accumulation area using MET-positron emission tomography (MET-PET). A total of 26 patients (median age, 69 years; 15 males) who had undergone tumor resection and MET-PET before and after surgery, after being newly diagnosed with GBM, were included in the study. MET-PET before and after tumor resection were compared. The association between the decrease in the maximum standardized uptake value (SUV) of the tumor divided by the normal cortical mean SUV (%; ΔT/N), the MET extent of resection (MET-EOR) from the % reduction in the MET accumulation area (%), and residual MET accumulation area (in cm3 ; MET-residual tumor volume [RTV]), as well as the survival time of patients with GBM, were evaluated via univariate analysis. ΔT/N were positively associated with survival (hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.97-0.99], p=.02). MET-RTV revealed a negative association with survival (HR, 1.02 [95% CI, 1.01-1.04], p=.04). Additionally, MET-EOR showed a strong trend with survival (HR, 0.99 [95% CI, 0.97-1.01], p=.06). Surgical resection of MET-accumulated areas in GBM significantly prolongs the survival of patients with GBM. However, a prospective large-scale multicenter study is needed to confirm our findings.

Dual-Tracer PET Image Separation by Deep Learning: A Simulation Study

Multiplexed positron emission tomography (PET) imaging provides perfectly registered simultaneous functional and molecular imaging of more than one biomarker. However, the separation of the multiplexed PET signals within a single PET scan is challenging due to the fact that all PET tracers emit positrons, which, after annihilating with a nearby electron, give rise to 511 keV photon pairs that are detected in coincidence. Compartment modelling can separate single-tracer PET signals from multiplexed signals based on the differences in bio-distribution kinetics and radioactive decay. However, the compartment-modelling-based method requires staggered injections and assumes that each tracer’s input function is known. In this paper, we propose a deep-learning-based method to simultaneously separate dual-tracer PET signals without explicitly knowing the input functions. We evaluate the proposed deep-learning-based separation method on dual-tracer [18F]FDG and [11C]MET PET simulations and compare its separation performance to that of the compartment-modelling-based method, assessing performance dependence on the time interval between tracer injections as well as on the amount of training data. It is shown that the proposed method implicitly denoises the separated images and offers reduced variance in the separated images compared to compartment modelling.

Sex-specific radiomic features of L-[S-methyl-11C] methionine PET in patients with newly-diagnosed gliomas in relation to IDH1 predictability.

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. 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 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. 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. 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.

COT-30 Effect of tumor resection in 11C methionine accumulation area on survival in patients with glioblastoma

Aim: The amount of tumor excised in an area enhanced by contrast medium on magnetic resonance imaging strongly affects the survival time of patients with glioblastoma. We investigated the effect of the amount of tumor removal in the 11C methionine (MET) accumulation site on overall survival(OS). Methods: Twenty-six patients (15 male; mean age, 68.9 years) with a diagnosis of glioblastoma who underwent tumor resection at Kizawa Memorial Hospital between June 1, 2015 and August 30, 2021 underwent MET-positron emission tomography (MET-PET) before and after the operation. In a comparison of MET-PET before and after tumor resection, the tumor-to-normal (T/N) ratio reduction (ΔT/N), MET accumulation area reduction (MET-extent of resection [EOR]), and the residual MET accumulation volume (MET-residual tumor volume [RTV]) were calculated. The relationship between these MET-related parameters associated with tumor resection and OS was investigated via univariable analysis. Results: Univariate analysis revealed that ΔT/N was significantly associated with OS (hazard ratio [HR]: 0.98; 95% confidence interval [CI]: 0.97–0.99; p=0.02). MET-RTV was also significantly associated with OS (HR: 1.01; 95% CI: 0.98–1.02; p=0.73) Conversely, MET-EOR (HR: 0.99; 95% CI: 0.97–1.01; p=0.06) was not significantly associated with OS. Conclusions: Aggressive surgical resection of the MET accumulation site significantly prolongs survival in patients with glioblastoma.

MET-PET and NGS Targeted Sequencing Guides Precision Medicine in a CNS Relapsed MM Patient

IntroductionCentral nervous system (CNS) involvement is an extremely rare manifestation of extramedullary multiple myeloma (MM), diagnosed in less than 1% of MM patients (pts). It is considered an ultimate high-risk feature, associated with unfavorable cytogenetics, and, even with intense treatment applied, survival is short, reaching less than 12 months in most cases.CaseAn 81y old male pt. with κ light chain MM on serum and urine, osteolytic lesions and bone marrow involvement in 2015, was referred to our institution. He presented with a CNS MM relapse in June 2017 after prior successful 1st line Bortezomib-based treatment. Cranial MRI confirmed multiple supra- und infratentoral lesions infiltrating the brain. His cerebrospinal fluid (CSF) demonstrated a high load of clonal plasma cells (PMCs) and κ free light chains (FLC), however, the disease was largely absent within the bone marrow of the patient.The use of positron emission tomography (PET) with 18F-2‘-deoxy-2‘-fluorodeoxyglucose (FDG) in MM has been strengthened by the recent publication of the updated imaging guidelines by the IMWG (Cavo et al., Lancet Oncol, 2017). Standard FDG based CNS imaging resolution, however, is impacted by the increased baseline glucose metabolism background of the brain. Therefore, we used radiolabeled 11C-methionine (MET) - that we recently identified as a sensitive imaging tracer in MM and in fact, high metabolic activity could be detected supra- and infratentorial as well as in the right femur and the clivus (Lapa et al., Theranostics, 2016).The pt. received 3 courses of an intrathecal triple therapy (Cytarabin, MTX, Dexamethasone) leading to a significant reduction of PMC-burden in the CSF. In addition, age adjusted systemic Thiotepa/Cytarabin-based therapy was applied, but had to be discontinued after one course of treatment as grade 4 neutropenia occurred with life-threatening septicemia.In parallel, we analyzed CD138+ cells obtained from BM and the CFS using customized next generation targeted sequencing (Ion torrent platform). The M3P (v 3.0) gene selection includes most commonly mutated MM genes, actionable drug targets and genes being associated with drug resistance. Average sequencing depth increased 700X and spatial MM heterogeneity was detected, as the CFS cells harbored a clonal BRAFV600E mutation, which was absent in the germline control and the bone marrow based CD138+ cells.We have initiated targeted therapy using the combination of Dabrafenib/Trametinib, known to be effective in BRAFV600E mutant melanoma brain metastases (Davies MA et al., Lancet Oncol, 2017); responses will be followed by combined cMRI and MET-PET imaging and results will be displayed at the meeting.Conclusion:This is an example of spatial genomic heterogeneity in MM and the first report of a patient with an isolated brain based BRAFV600E mutated MM tumor. This patient with otherwise very limited perspective leverages from innovative diagnostics including MET PET and targeted genome sequencing, demonstrating their clinical utility as they provide the basis for precision medicine concepts to be applied in this MM patient. [Display omitted] DisclosuresStewart:Amgen: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Roche: Consultancy; Bristol-Myers Squibb: Consultancy.

Voxelwise Principal Component Analysis of Dynamic [S-Methyl-11C]Methionine PET Data in Glioma Patients.

Simple SummaryRecent works on dynamic amino acid positron emission tomography (PET) imaging of gliomas have highlighted characteristic behaviors of time-activity curves (TACs) extracted from the whole tumor w.r.t. the grade, genotype, and outcome. However, gliomas are known to be highly heterogeneous tumors. Here, we aim at highlighting similar dynamic behaviors at the voxel level within the tumor volume in [S-methyl-11C]methionine PET data of 33 glioma patients using principal component analysis (PCA). The PCA model was derived from TACs of 20 patients and subsequently applied to 13 other patients in whom our approach was shown to outperform classical pharmacokinetic modeling to this end. Our parameter-free approach provides additional parametric maps from dynamic methionine PET scans with little modification of the routine protocol and no arterial sampling. This early methodological work paves the way for various clinical studies on glioma heterogeneity with applications for treatment planning and response evaluation.Recent works have demonstrated the added value of dynamic amino acid positron emission tomography (PET) for glioma grading and genotyping, biopsy targeting, and recurrence diagnosis. However, most of these studies are based on hand-crafted qualitative or semi-quantitative features extracted from the mean time activity curve within predefined volumes. Voxelwise dynamic PET data analysis could instead provide a better insight into intra-tumor heterogeneity of gliomas. In this work, we investigate the ability of principal component analysis (PCA) to extract relevant quantitative features from a large number of motion-corrected [S-methyl-11C]methionine ([11C]MET) PET frames. We first demonstrate the robustness of our methodology to noise by means of numerical simulations. We then build a PCA model from dynamic [11C]MET acquisitions of 20 glioma patients. In a distinct cohort of 13 glioma patients, we compare the parametric maps derived from our PCA model to these provided by the classical one-compartment pharmacokinetic model (1TCM). We show that our PCA model outperforms the 1TCM to distinguish characteristic dynamic uptake behaviors within the tumor while being less computationally expensive and not requiring arterial sampling. Such methodology could be valuable to assess the tumor aggressiveness locally with applications for treatment planning and response evaluation. This work further supports the added value of dynamic over static [11C]MET PET in gliomas.

BIMG-06. RESPONSE ASSESSMENT OF BEVACIZUMAB THERAPY FOR GLIOBLASTOMA BY USING MULTIPLE PET TRACERS

OBJECTIVEUse of the positron emission tomography (PET), such as 18F-fluorodeoxyglucose (FDG), 11C-Methionine (MET), 18F- Fluorothymidine (FLT), and 18F-Fluoromisonidazole (FMISO), is expected to lead the way for novel applications aimed at achieving efficient malignancy grading and treatment of gliomas. The aim of this study was to assess FDG, MET, FLT, and FMISO PET studies to evaluate the biological effects induced by bevacizumab (BEV) therapy in glioblastoma patients.METHODSSeventy-one patients with glioblastoma were treated biweekly with BEV from July 2013 to November 2020. FDG, MET, FLT, and FMISO PET scans were obtained at baseline and at follow-up (4 weeks after treatment onset). Measures of FDG, MET, FLT, and FMISO avidity were recorded; the measures were SUVmax, metabolic tumor volume (MTV; volume of tumor with SUV>42% of SUVmax), SUVmean (within the MTV), tumor-to-normal ratio (TNR), tumor-to blood ratio (TBR), and total lesion avidity (TLA; calculated as MTV x SUVmean). The prognostic analysis was performed in relation to the response assessment by multiple PET tracers using progression-free survival (PFS) and overall survival (OS).RESULTSUnder the assessment of the Cox proportional hazard model, increased changes of FDG SUVmax, MET TLA at follow-up, FLT TLA at follow up, increased changes of FLT TLA, increased changes of FMISO TBR and FMISO MTV were significant prognostic factor of PFS. Increase changes of FDG TLA and FLT TLA and increased changes of FMISO TBR were significant prognostic factor of OS.CONCLUSIONIncreased changes in FLT TLA and FMISO-PET after BEV therapy may be a useful biomarker for predicting PFS and OS in glioblastoma.

Preliminary clinical assessment of dynamic carbon-11 methionine positron-emission tomography/computed tomography for the diagnosis of the pathologies in patients with musculoskeletal lesions: a prospective study

BackgroundThis study prospectively assessed the diagnostic capacity of dynamic carbon-11 methionine (C-11 MET) positron-emission tomography (PET)/computed tomography for the diagnosis of pathologies in patients with primary unknown musculoskeletal lesions (MSLs). In total, 13 patients with MSLs underwent dynamic scans (5–10 [phase 1], 10–15 [phase 2], 15–20 [phase 3], 20–25 [phase 4], 25–30 [phase 5], and 30–35 [phase 6] min post-injection of C-11 MET). We statistically compared the maximum standardised uptake values (SUVmax) and corresponding retention index for dynamic scans (RI-SUV) for five benign MSLs (BMSLs), five primary malignant musculoskeletal tumours (PMMSTs), four metastatic musculoskeletal tumours (MMSTs), and three malignant lymphoma (ML) cases and explored their diagnostic capacities using receiver operating characteristic (ROC) curve analyses.ResultsSUVmax gradually decreased or remained similar with minimal fluctuations in all BMSL cases and four of five PMMST cases. In contrast, SUVmax increased over time in one case of PMMST and in all cases of MMST and ML. Significant differences were observed in SUVmax for all time phases and RI-SUV between BMSLs and MMSLs, in SUVmax for all time phases between PMMSTs and BMSLs, in SUVmax for all time phases and RI-SUV between non-PMMST-malignant tumours and BMSL, and in RI-SUV between non-PMMST-malignant tumours and PMMST. In ROC analyses, the areas under the curve yielded the highest values at 1.00 for differentiating most intergroup comparisons.ConclusionsDynamic C-11 MET PET scans have the potential to be good predictors of discriminating MSLs in patients with primary unknown MSLs in clinical practice.

Diagnostic accuracy of 13N-ammonia PET, 11C-methionine PET and 18F-fluorodeoxyglucose PET: a comparative study in patients with suspected cerebral glioma

BackgroundThe treatment of patients with glioma depended on the nature of the lesion and on histological grade of the tumor. Positron emission tomography (PET) using 13N-ammonia (NH3), 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) have been used to assess brain tumors. Our aim was to compare their diagnostic accuracies in patients with suspected cerebral glioma.MethodsNinety patients with suspicion of glioma based on previous CT/MRI, who underwent NH3 PET, MET PET and FDG PET, were prospectively enrolled in the study. The reference standard was established by histology or clinical and radiological follow-up. Images were interpreted by visual evaluation and semi-quantitative analysis using the lesion-to-normal white matter uptake ratio (L/WM ratio).ResultsFinally, 30 high-grade gliomas (HGG), 27 low-grade gliomas (LGG), 10 non-glioma tumors and 23 non-neoplastic lesions (NNL) were diagnosed. On visual evaluation, sensitivity and specificity for differentiating tumors from NNL were 62.7% (42/67) and 95.7% (22/23) for NH3 PET, 94.0% (63/67) and 56.5% (13/23) for MET PET, and 35.8% (24/67) and 65.2% (15/23) for FDG PET. On semi-quantitative analysis, brain tumors showed significantly higher L/WM ratios than NNL both in NH3 and MET PET (both P < 0.001). The sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic (ROC) analysis, respectively, were 64.2, 100% and 0.819 for NH3; and 89.6, 69.6% and 0.840 for MET. Besides, the L/WM ratios of NH3, MET and FDG PET in HGG all significantly higher than that in LGG (all P < 0.001). The predicted (by ROC) accuracy of the tracers (AUC shown in parentheses) were 86.0% (0.896) for NH3, 87.7% (0.928) for MET and 93.0% (0.964) for FDG. While no significant differences in the AUC were seen between them.ConclusionNH3 PET has remarkably high specificity for the differentiation of brain tumors from NNL, but low sensitivity for the detection of LGG. MET PET was found to be highly useful for detection of brain tumors. However, like FDG, high MET uptake is frequently observed in some NNL. NH3, MET and FDG PET all appears to be valuable for evaluating the histological grade of gliomas.

Quantitative volumetric analysis of primary glioblastoma multiforme on MRI and 11C-methionine PET: initial study on five patients.

To investigate the discrepancy between 11C-methionine (MET) positron emission tomography (PET) and MRI results in primary glioblastoma multiforme (GBM) through three-dimensional (3D) volumetric analysis, we retrospectively analysed patients with primary GBM who underwent preoperative 3D MRI and MET PET and were operated between June 2016 and January 2017. Tumour delineation and volumetric analysis were conducted using MRIcron software. Tumour volumes defined by MRI (VMRI) were manually drawn slice by slice in axial and sagittal or coronal images of enhanced T1 sequence, while metabolic tumour volumes were automatically segmented in MET PET (VMET) based on three (frontal, occipital and temporal) 3D reference volumes of interest (VOI). Discrepancies were evaluated in terms of both absolute volume and percentage on the combined images. MET PET contours contained and extended beyond MRI contours in all five patients; in a subset of cases, MET PET contours extended to the contralateral hemisphere. The discrepancy between MET uptake and MRI results was 27.67 cm3 (4.20-51.20 cm3), i.e. approximately 39.0% (17.4-64.3%) of the metabolic tumour volume was located outside the volumes of the Gd-enhanced area. Metabolic tumour volume is substantially underestimated by Gd-enhanced area in patients with primary GBM. Quantitative volumetric information derived from MET uptake is useful in defining tumour targets and designing individualised therapy strategies in primary GBM.

Discrimination between primary low-grade and high-grade glioma with 11C-methionine PET: a bivariate diagnostic test accuracy meta-analysis.

To perform a meta-analysis evaluating the diagnostic accuracy of11C-methionine (MET) positron emission tomography (PET) to discriminate between primary low-grade glioma (LGG) and high-grade glioma (HGG). A systematic database search was performed by a librarian in relevant databases with the latest search on 07November 2016. Hitswere assessed for inclusionindependently by two authors. Individual patient data on relative MET uptake was extracted on patients examined pre-operatively with MET PET and subsequent neuropathological diagnosis of astrocytoma or oligodendroglioma. Individual patient datawere analysed for diagnostic accuracy using a bivariate diagnostic random-effects meta-analysis model with restricted maximum likelihood estimation method. Bivariate meta-regression and subgroup analyses assessed study heterogeneity and validity.This study is registered with PROSPERO, number CRD42016050747. Out of 1828 hits, 13 studies comprising of241 individuals were included in the quantitative and qualitative analysis. MET PET had an area under the bivariate summary receiver operating characteristics curve of 0.78 to discriminate between LGG and HGG and a summary sensitivity of 0.80 with 95%confidence interval (CI) (0.66-0.88) and a summary false positive rate of 0.28, 95% CI(0.19-0.38). Heterogeneity was described by; bias in patient inclusion, study quality, and ratio method. Optimal cutoff for relative MET uptake was 2.21. MET PET had a moderately high diagnostic accuracy for the discrimination between primary LGG and HGG. Advances in knowledge: MET PET can be used as a clinical tool for the non-invasive discrimination between LGG and HGG with a moderately high accuracy at cut-off 2.21.

Analysis of progression and recurrence of meningioma using 11C-methionine PET

The recurrence rate of meningioma after surgery is high, and progression is often observed. The risk factors for recurrence and progression are not clear. We evaluated the risk factors for recurrence and progression in meningioma using (11)C-methionine (MET) positron emission tomography (PET). Thirty-seven patients (mean follow-up, 80 months) with an intracranial meningioma were enrolled. MET PET was performed before treatment between 1995 and 2010, and patients were followed up in an out-patient clinic. Surgery was performed in 33 patients, and a wait-and-see approach was taken in four patients. We evaluated the extent of tumor resection, location, WHO grade, Ki-67 labeling index, and lesion to normal ratio (LN ratio) of MET uptake. Six of the surgical cases had a recurrence, and two of the observation-only patients had tumor progression. A high LN ratio of MET uptake was a significant risk factor for recurrence and progression with univariate analysis. The area under the curve of receiver operating characteristic curve for the LN ratio of MET uptake was 0.754, and the optimal cutoff value was 3.18 (sensitivity 63 %, specificity 79 %). With multivariate analysis, a high LN ratio of MET uptake, non-gross total resection, and a high WHO grade were significant risk factors for progression and recurrence. A high LN ratio of MET uptake was a risk factor for tumor progression and recurrence. The advantage of MET PET is that it is not invasive and can easily be used to evaluate the whole tumor.

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

Fluorine-18 ((18)F) 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 ((11)C MET) has little uptake under normal conditions. We prospectively investigated the uptake of (18)F FDG and (11)C MET PET in patients with craniopharyngioma prior to proton therapy. Ten patients newly diagnosed with craniopharyngioma underwent PET imaging using (18)F FDG and (11)C 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. 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). (11)C 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 (11)C MET PET to discriminate between active and inactive tumor after irradiation.

11c-Methionine Positron Emission Tomography May Monitor the Activity of Encephalitis

Encephalitis is generally diagnosed by clinical symptoms, cerebrospinal fluid examination, and imaging studies including CT, magnetic resonance imaging (MRI), and perfusion single photon emission tomography (SPECT). However, the role of positron emission tomography (PET) in diagnosis of encephalitis remains unclear. A 49-year-old woman presenting with coma and elevated inflammatory reaction was diagnosed as having encephalitis according to slow activity on electroencephalogram, broad cortical lesion in MR fluid attenuated inversion recovery image, and increased blood flow demonstrated by SPECT. PET revealed increased accumulation of (11)C-methionine (MET) in the affected brain tissues. After the symptom had improved 2 months later, the accumulation of MET as well as the abnormal findings of MR imaging and SPECT was normalized. This case indicated that MET PET may monitor the activity of encephalitis.

Comparison of 11C-Methionine PET and 18F-FDG PET in Patients with Primary Central Nervous System Lymphoma

2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET) has been used as a promising tool to diagnose primary central nervous system (CNS) lymphoma because the tumor shows very high FDG accumulation. Although (11)C-methionine (MET) PET has been reported to be useful for evaluating various brain tumors, the role of MET PET in CNS lymphoma is unclear. We compared the uptake of MET and FDG in patients with CNS lymphoma. Thirteen immunocompetent patients with CNS lymphoma were examined. All patients underwent PET with MET (15 min p.i.) and FDG (60 min p.i.). PET results were evaluated by visual and semi-quantitative analysis. For semi-quantitative analysis, the standardized uptake value (SUV) and tumor to contralateral normal brain tissue (T/N) ratio were determined by region-of-interest analysis. For detection of CNS lymphoma, sensitivity of PET using both MET and FDG was 100%. The mean (±SD) value of SUV in the contralateral normal brain tissue using MET (1.43 ± 0.21) was significantly lower than that using FDG (5.58 ± 1.79; p < 0.002). The mean (±SD) value of SUV in the CNS lymphoma using MET (4.27 ± 1.91) was significantly lower than that of FDG (13.94 ± 5.65; p < 0.002). There were no significant differences between mean (±SD) T/N ratios using MET PET (3.00 ± 1.26) and FDG PET (2.74 ± 1.25). There was no significant difference between T/N ratios using MET PET and FDG PET, although uptake of MET in CNS lymphoma was significantly lower than that of FDG. MET PET showed as high a sensitivity as FDG PET for the detection of primary lesions in patients with CNS lymphoma.

Detection of histological anaplasia in gliomas with oligodendroglial components using positron emission tomography with 18F-FDG and 11C-methionine: report of two cases

Gliomas are regionally heterogeneous tumors. Positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) and (11)C-methionine (MET) evaluates the heterogeneity of histological malignancy within the tumor. We present two patients with oligodendrocytic tumors that showed discrepancies in the highest uptake areas with these two tracers. PET studies with MET and FDG were performed on the same day, 2 weeks before surgery. In both cases, biopsy specimens were separately obtained from the highest MET and FDG uptake areas guided by intraoperative neuronavigation. Histological examinations demonstrated that the specimens from the highest MET uptake area revealed low-grade oligoastrocytoma or oligodendroglioma, whereas histological anaplasias were contained in the specimens from the highest FDG uptake area. With gliomas with oligodendroglial components, the MET uptake ratio does not always correspond to histological anaplasia, which can be detected only by FDG PET. Sole application of MET PET for preoperative evaluation may lead to misunderstanding of histological heterogeneity in gliomas, especially those with oligodendroglial components. FDG and MET tracers play complementary roles in preoperative evaluation of gliomas.

A Study on the Prognostic Evaluation of Carbon Ion Radiotherapy for Head and Neck Adenocarcinoma with C-11 Methionine PET

Carbon ion radiotherapy (CIRT) has been developed, and a phase I/II CIRT trial has been conducted in patients with adenocarcinoma in the head and neck region. We evaluated whether the L-methyl [11C]-methionine (MET) uptake could be an early predictor for local recurrence, metastasis, and the prognosis in patients with adenocarcinoma in the head and neck region. Twenty-six patients were prospectively studied by MET-positron emission tomography (PET) before and about 1 month after CIRT. The tumor MET uptake was measured with the semiquantitative tumor to normal tissue ratio (TNR). The tumor TNR and relevant clinical parameters were then evaluated by both univariate and multivariate analyses. The average TNRs before and after the treatment were 6.2 (± 2.2) and 3.9 (± 1.7), respectively, and significant differences were observed between them. In a univariate analysis, both local recurrence and metastasis were observed more frequently in the group with a higher TNR before and after the treatment than a lower TNR, and the prognosis was also poor. The cut-off values were 9.3, 4.9, and 5.1 before the treatment and 4.9, 4.2, and 4.3 after the treatment, respectively. In the rate of TNR changes before and after the treatment, metastasis was observed more frequently in the group with lower rates of change, and the prognosis was poor. The cut-off values for metastasis and prognosis determination were 18.0% and 16.9%, respectively. In a multivariate analysis, significant differences were observed for all relationships except for the relationship between the TNR before the treatment and local recurrence. Significant differences were observed for metastasis and prognosis in the rate of TNR changes before and after the treatment. The determination of treatment effectiveness using TNR in CIRT for head and neck adenocarcinoma is an independent factor for predicting local recurrence, the incidence of metastasis, and the prognosis. MET-PET is therefore considered to be useful for determining the treatment effectiveness in patients with head and neck adenocarcinoma undergoing CIRT.

Detection of bone metastases using diffusion weighted magnetic resonance imaging: comparison with 11C-methionine PET and bone scintigraphy

We evaluated the ability of diffusion-weighted imaging (DWI) to detect bone metastasis by comparing the results obtained using this modality with those obtained using (11)C-methionine (MET) positron emission tomography (PET) and bone scintigraphy. This retrospective study involved 29 patients with bone metastasis. DWI was obtained using a single-shot echo planar imaging (EPI) sequence with fat suppression using a short inversion time inversion recovery sequence. The detection capabilities of DWI for bone metastases were compared with those of whole body MET PET (in 19 patients) and 99mTc-methylene diphosphonate bone scintigraphy (in 15 patients). Among the 19 patients who were diagnosed using DWI and PET, the PET identified 39 bone metastases, while the DWI identified 60 metastases out of 69 metastases revealed with conventional magnetic resonance imaging (MRI). Among the 15 patients who were diagnosed using DWI and bone scintigraphy, the bone scintigraphy identified 18 bone metastases, while the DWI identified 72 metastases out of 78 metastases revealed with conventional MRI. The overall bone metastasis detection rates were 56.5% for PET, 23.1% for bone scintigraphy and 92.3% for DWI. DWI is a very sensitive method for detecting bone metastasis and is superior to MET PET and bone scintigraphy in terms of its detection capabilities.

Preliminary study of carbon-11 methionine PET in the evaluation of early response to therapy in advanced breast cancer

Breast cancer is one of the principal oncological challenges in the Western world. Currently, there are only a few reliable predictive methods for monitoring treatment. We investigated the ability of carbon-11 methionine ("11C-MET) positron emission tomography (PET) to evaluate early response to therapy in advanced breast cancer. Thirteen patients with metastases in the lungs/pleura, lymph nodes, soft tissue, or bones entered a MET PET study both before and after the first cycle of polychemotherapy (n=4), or after the first month of therapy with hormones (n=5), or low dose weekly cytostatics (n=3). One patient underwent three PET studies: before hormonal therapy, after 1 month of hormonal therapy, and after the first cycle of polychemotherapy (total, 27 studies). MET accumulation in the metastatic sites was measured as standardized uptake values (SUVs), and the pretreatment and post-treatment SUVs were compared with each other and the clinical follow-up data. A total of 26 different metastatic sites were investigated in 13 patients. All metastases were visible by MET PET except one superficially spreading local skin recurrence, probably because of respiratory movements. Five new metastatic sites were detected. After therapy the SUVs decreased significantly (30-54%; P < 0.05) in all six responding metastatic sites, whereas the SUVs of nonresponding metastases decreased somewhat (11-130/%; n=4), remained stable (+/- 8%; n=10), or increased (13-23%; n=4) (P=NS). The SUVs of two nonresponding metastatic sites decreased clearly. Physiological MET uptake in the salivary glands, the myocardium, and the bone marrow did not disturb the image interpretation. MET PET may be useful in assessing the early response to therapy in advanced breast cancer.