11C-methionine PET Research Articles

NI-3 Magnetic resonance relaxometry for tumor cell density imaging for glioma: An exploratory study via 11C-methionine PET and its validation via stereotactic tissue sampling

Objective: While visualization of non-enhancing tumors for glioma is crucial for planning the most appropriate surgical or non-surgical treatment of the disease, current MRI cannot achieve this goal. This study aims to test the hypothesis that quantitative and diffusion MRI can estimate tumor burden with the brain. Materials and Methods: Study 1: Ten patients who have undergone Methionine PET (Met-PET), quantitative MRI (qMRI), and diffusion MRI (DWI) were included for analysis. A cut-off of a tumor-to-normal ratio (T/Nr) 1.5 was set on Met-PET, and the values from qMRI and DWI were compared. Study 2: Seventy-nine stereo-tactically sampled tissues from 22 glioma patients were correlated with Met-PET, qMRI, and DWI measurements regarding tumor cell density. qMRI acquisition: Imaging was performed on either a 1.5 or 3 T MR scanner (Prisma or Aera; Siemens Healthcare, Erlangen, Germany). T1-relaxometry was achieved by first acquiring MP2RAGE images, then converting those images into T1-relaxation time maps. At the same time, T2-relaxometry was achieved by first acquiring multi-echo T2-weighted images and then converting those images into T2-relaxation time maps, with both relaxometries performed via Bayesian inference modeling (Olea Nova+; Canon Medical Systems, Tochigi, Japan). Results: Study 1 revealed that regions of 1850ms < T1-relaxation time < 3200ms and 115ms < T2-relaxation time < 225ms tended to be Met-PET T/Nr > 1.5. DWI was not useful to separate areas between low and high Met-PET. Study 2 showed that regions of 1850ms < T1-relaxation time < 3200ms showed high tumor cell density than other areas (p=0.04). Conclusions: Our results supported the hypothesis that qMRI is useful for predicting the tumor load within the brain among glioma patients. T1-relaxation time was notably useful for this means. On the other hand, ADC measured from DWI was limited for tumor load prediction.

P14.59 Rapid early progression of glioblastoma is not related to cortical/neural stem cells regions

Abstract BACKGROUND Rapid early progression (REP) of glioblastoma after surgery observed on pre-radiotherapy MRI scan is common. Subventricular zone (SVZ) and hippocampal regions are supposed to harbor astrocyte-like neural stem cells (NSC) with tumors arising from these transformed stem cells threatening of higher risk of REP. REP is defined as a new enhancing tumor or &amp;gt;25% increase in enhancement before radiotherapy. Lim′s classification of initial glioblastoma location related to these NSC regions predicts invasive and multifocal tumor phenotype. Glioblastomas are classified preoperatively into four groups by the spatial relationship of the contrast-enhancing lesion with the SVZ and cortex. The aim of this retrospective single-institutional study is to evaluate the relations of this Lim classification on REP in unselected cohort of glioblastoma patients. MATERIAL AND METHODS Patients receiving radiotherapy between 2014–2017 were analyzed, 95 were evaluable. 47 patients (30.5%) were treated with the Stupp regimen. Lim1 classification (contact with cortex as well as SVZ) was presented in 74(48%) patients, Lim2 (contact with SVZ only) in 22(14.3%), Lim3 (contact with cortex only) in 50(32.5%) and Lim4 in 8(5.2%) patients. A total of 52% of patients developed REP. RESULTS Significantly better overall survival was with Stupp regimen (23.3 vs. 8.6 months, p&amp;lt;0.001) and without REP (18.5 vs. 10.2 months, p=0.001). There was no significant impact of time to start of radiotherapy. No significant relation between REP and Lim classification was observed. CONCLUSION The initial location is not predictive for REP. Patients experiencing REP have significantly worse overall survival and modification of their management represents an urgent unmet clinical need. Molecular and clinical biomarkers indicating an increased risk of REP are needed.Presented will also be an already published analysis of clinical factors associated with REP in glioblastoma and the effect of REP and treatment on survival outcomes. Newly, we will introduce the investigator-initiated prospective academic clinical trial (GlioMET) focused on optimization of glioblastoma radiotherapy by 11C-Methionine PET scan in patients with REP. Supported by Ministry of Health of the Czech Republic AZV, No.18-03-00469 and AZV NU20-03-00148.

Investigation of histological heterogeneity based on the discrepancy between the hyperintense area on T2-weighted images and the accumulation area on 11C-methionine PET in minimally enhancing glioma

IntroductionThe objective of the study was to investigate the correlation between differences between imaging modalities and histological heterogeneity in minimally enhancing glioma. MethodsA prospective study was performed in 11 patients with minimally enhancing glioma (<1 cm3 volume) in the T2 or FLAIR hyperintense (T2/FL+) area who simultaneously underwent 11C-methionine (MET)-PET, and had a volume-based discrepancy between the T2/FL+ area and MET accumulation (MET+) area (tumor to normal cortex (T/N) ratio ≥1.3) of >10%. The correlation between the imaging discrepancy and histological heterogeneity was investigated. ResultsThe average T/N ratio for the T2/FL+/MET+ area in grade II glioma (2.08 ± 0.4) was smaller than that in grade III (4.19 ± 2.4), whereas that for the T2/FL+/MET− area was similar in grade II (1.07 ± 0.2) and III (1.07 ± 0.1). The average T/N ratio for the T2/FL+/MET+ area in grade II and III was higher than that for the T2/FL+/MET− area (p < 0.0005 for grade II, p < 0.05 for grade III). In the T2/FL+/MET− area, 8 cases showed no neoplastic features, while the other 3 cases had neoplastic features with comparatively lower grade than the T2/FL+/MET+ area. The volumetric ratio of the MET+ area (16.8 ± 16.0 cm3) to the T2/FL+ area (41.5 ± 20.9 cm3) was 43.4%, and the volumetric difference in grade II cases (61.6%) tended to larger than that in grade III (50.6%). In immunohistochemical findings, the only MIB1 labeling index differed between grade II (5.5 ± 2.1) and III (23.2 ± 18.0) with significantly difference. In the T2/FL+/MET− area, 3 of 6 grade II gliomas had neoplastic features, whereas all 5 grade III gliomas had normal brain including one gliosis histologically. ConclusionThe discrepancy between the T2/FL+ and MET+ areas could reflect spatial heterogeneity in histological findings. An understanding of the correlation between imaging and pathology based on spatial heterogeneity may assist with appropriate diagnosis and treatment for patients with glioma.

11C-Methionine PET for Identification of Pediatric High-Grade Glioma Recurrence.

Differentiating tumor recurrence or progression from pseudoprogression during surveillance of pediatric high-grade gliomas (PHGGs) using MRI, the primary imaging modality for evaluation of brain tumors, can be challenging. The aim of this study was to evaluate whether 11C-methionine PET, a molecular imaging technique that detects functionally active tumors, is useful for further evaluating MRI changes concerning for tumor recurrence during routine surveillance. Methods: Using 11C-methionine PET during follow-up visits, we evaluated 27 lesions in 26 patients with new or worsening MRI abnormalities for whom tumor recurrence was of concern. We performed quantitative and qualitative assessments of both 11C-methionine PET and MRI data to predict the presence of tumor recurrence. Further, to assess for an association with overall survival (OS), we plotted the time from development of the imaging changes against survival. Results: Qualitative evaluation of 11C-methionine PET achieved 100% sensitivity, 60% specificity, and 93% accuracy to correctly predict the presence of tumors in 27 new or worsening MRI abnormalities. Qualitative MRI evaluation achieved sensitivity ranging from 86% to 95%, specificity ranging from 40% to 60%, and accuracy ranging from 85% to 89%. The interobserver agreement for 11C-methionine PET assessment was 100%, whereas the interobserver agreement was only 50% for MRI (P < 0.01). Quantitative MRI and 11C-methionine PET evaluation using receiver-operating characteristics demonstrated higher specificity (80%) than did qualitative evaluations (40%-60%). Postcontrast enhancement volume, metabolic tumor volume, tumor-to-brain ratio, and presence of tumor as determined by consensus MRI assessment were inversely associated with OS. Conclusion:11C-methionine PET has slightly higher sensitivity and accuracy for correctly predicting tumor recurrence, with excellent interobserver agreement, than does MRI. Quantitative 11C-methionine PET can also predict OS. These findings suggest that 11C-methionine PET can be useful for further evaluation of MRI changes during surveillance of previously treated PHGGs.

Oncological and functional outcomes of supratotal resection of IDH1 wild-type glioblastoma based on 11C-methionine PET: a retrospective, single-center study

The oncological and functional outcomes in glioblastoma (GBM) patients following supratotal resection (SupTR), involving complete resection of contrast-enhancing enhanced (CE) tumors and areas of methionine (Met) uptake on 11C-met positron emission tomography (Met-PET), are unknown. We conducted a retrospective review in newly diagnosed, IDH1 wild-type GBM patients, comparing SupTR with gross total resection (GTR), in which only CE tumor tissue was resected. All patients underwent standard radiotherapy and temozolomide treatment, and were followed for tumor recurrence and overall survival (OS). Among the 30 patients included in this study, 7 underwent SupTR and 23 underwent GTR. Awake craniotomy with cortical and subcortical mapping was more frequently performed in the SupTR group than in the GTR group. During the follow-up period, significantly different patterns of disease progression were observed between groups. Although more than 80% of recurrences were local in the GTR group, all recurrences in the SupTR group were distant. Median OS in the GTR and SupTR groups was 18.5 months (95% confidence interval [CI] 14.2–35.1) and not reached (95% CI 30.5-not estimable), respectively; this difference was statistically significant (p = 0.03 by log-rank test). No postoperative neurocognitive decline was evident in patients who underwent SupTR. Compared to GTR alone, aggressive resection of both CE tumors and areas with Met uptake (SupTR) under awake craniotomy with functional mapping results in a survival benefit associated with better local control and neurocognitive preservation.

OTEH-4. Deeper insight into intratumoral heterogeneity by MRI and PET-guided stereotactic biopsies from glioblastoma patients

Glioblastoma is one of the most aggressive cancers, but the molecular evolution is still not fully understood. We used PET imaging combined with deep sequencing of glioblastoma biopsies at both the RNA and DNA levels to get a deeper insight into molecular evolution. In the clinical setting, PET imaging provides information about metabolically active tumor areas, but the molecular interpretation is unclear. Our primary objective was to perform an intratumoral spatial comparison of biopsies from potentially aggressive and less aggressive areas in glioblastomas according to PET scans. Additionally, tissue from the tumor periphery was included. We used MRI, 11C-methionine(MET) PET, and 18F-FDG PET was used in combination to obtain a series of neurosurgical stereotactic biopsies from tumor areas with high MET and 18F-FDG uptake (hotspot), low MET and 18F-FDG uptake (coldspot), as well as tumor periphery of six glioblastoma patients that were processed for whole genome, exome, and transcriptome sequencing. Differential gene expression and gene ontology analysis showed that hotspots were enriched in gene sets associated with DNA replication, cell cycle, and ligand receptor interaction. Genome and exome analysis suggested hotspots and coldspots to have similar mutational profiles. However, a limited number of hotspot-specific mutations and fusion transcripts indicated that hotspot tumor cells developed from coldspot cells and point at the potential role of hotspot driver genes in glioblastoma. Our findings reveal that hotspots in glioblastomas represent a more advanced stage of molecular evolution than coldspots.

Using Molecular Imaging to Enhance Decision Making in the Management of Pituitary Adenomas.

In most patients with suspected or confirmed pituitary adenomas (PAs), MRI, performed using T1- (with or without gadolinium enhancement) and T2-weighted sequences, provides sufficient information to guide effective clinical decision making. In other patients, additional MR sequences (e.g., gradient recalled echo, fluid-attenuation inversion recovery, MR elastography, or MR angiography) may be deployed to improve adenoma detection, assess tumoral consistency, or aid distinction from other sellar/parasellar lesions (e.g., aneurysm, meningioma). However, there remains a small but important subgroup of patients in whom primary or secondary intervention (e.g., first or redo transsphenoidal surgery, stereotactic radiosurgery) is limited by the inability of MRI to accurately localize the site(s) of de novo, persistent, or recurrent PA. Emerging evidence indicates that hybrid imaging, which combines molecular (e.g. 11C-methionine PET) and cross-sectional (MRI) modalities, can enable the detection and precise localization of sites of active tumor to guide targeted intervention. This not only increases the likelihood of achieving complete remission with preservation of remaining normal pituitary function but may mitigate the need for long-term (even lifelong) high-cost medical therapies. Here, we review published evidence supporting the use of molecular imaging in the management of PAs, including our own 10-y experience with 11C-methionine PET.

PSMA Expression in 122 Treatment Naive Glioma Patients Related to Tumor Metabolism in 11C-Methionine PET and Survival.

Apart from its expression in benign and malignant prostate tissue, prostate specific membrane antigen (PSMA) was shown to be expressed specifically in the neovasculature of solid tumors. For gliomas only little information exists. Therefore, we aimed to correlate PSMA expression in gliomas to tumor metabolism by L-[S-methyl-11C]methionine (MET) PET and survival. Therefore, immunohistochemical staining (IHC) for isocitrate dehydrogenase 1-R132H (IDH1-R132H) mutation and PSMA expression was performed on the paraffin embedded tissue samples of 122 treatment-naive glioma patients. The IHC results were then related to the pre-therapeutic semiquantitative MET PET data and patients’ survival. Vascular PSMA expression was observed in 26 of 122 samples and was rather specific for high-grade gliomas ([HGG] 81% of glioblastoma multiforme, 10% of WHO grade III and just 2% of grade II gliomas). Significantly higher amounts of gliomas without verifiable IDH1-R132H mutation showed vascular PSMA expression. Significantly shorter median survival times were seen for patients with vascular PSMA staining in all tumors as well as HGG only. Additionally, significantly higher numbers of PSMA staining vessels were found in tumors with high amino acid metabolic rates. Vascular PSMA expression in gliomas was seen as a high-grade specific feature associated with elevated amino acid metabolism and short survival.

Prognostic Significance of Interim 11c-Methionine PET for the Treatment of Primary Central Nervous System Lymphoma (PCNSL)

Background: Lymphoma arising in the central nervous system (CNS) has a dismal prognosis. Although the International Extranodal Lymphoma Study Group (IELSG) scoring system and Memorial Sloan-Kettering Cancer Center (MSKCC) index have been proposed to determining prognosis for patients with PCNSL at diagnosis, there is few study about prognostic factor at mid-treatment. In systemic lymphoma, many clinical studies demonstrated the prognostic significance of interim PET/CT. However, the prognostic role of interim PET/CT in PCNSL is uncertain.Purpose: This study prospectively investigated that 11C-methionine PET-CT (11C-MET PET) may provide additional prognostic information of mid-response assessment prior to completion of chemotherapy in PCNSL.Methods: Thirty newly diagnosed patients with PCNSL were enrolled between November 2013 and August 2016. Both brain MRI and 11C-MET PET analysis were performed at the time of diagnosis and after four infusions of high-dose MTX in induction chemotherapy. The clinical prognostic factor was assessed according to International Extranodal Lymphoma Study Group (IESLG) scoring system. Tumor to normal tissue ratio (T/N ratio) and metabolic tumor volume (MTV) were estimated as the indices of interim 11C-MET PET. The optimal cutoff values of T/N ratio and MTV for predicting outcome of PCNSL were identified by receiver operating characteristic (ROC) curve. Survival outcomes were analyzed using the Kaplan-Meier survival curves according to the T/N ratio and MTV of interim PET/CT. The prognostic values of interim T/N ratio and MTV were evaluated by uni- and multivariate cox-regression analysis.Results: All patients had diffuse large B cell lymphoma with median age of 65.3 years (range: 55-75). Four patients could not be evaluated the interim 11C-MET PET due to disease progression or treatment-related mortality. Four patients proceeded to frontline autologous stem cell transplantation as a consolidation. Patients were categorized into low (N=5, 19.2%), intermediate (N=11, 42.3%) and high (N=10, 38.5%) risk groups according to IELSG prognostic score. Fourteen patients developed a recurrence with median follow-up of 21 months. The discrepancy of interim response between 11C-MET PET and MRI occurred in 4 patients. Whereas no metabolic viable lesions were detected based on interim 11C-MET PET, the remnant contrast enhancing lesions were detected on interim MRI. All four patients achieved complete remission after primary treatment. Progression-free survival (PFS) significantly differed between patients with high and low groups in both of interim T/N ratio (P= 0.003) and MTV (P = 0.023) by the log-rank test. Multivariate cox regression analysis showed a high interim T/N ratio (> 1.67) was significantly associated with a worse progression-free survival (95% CI, 1.03-13.08; P= 0.044).Conclusion: Interim11C-MET PET based on T/N ratio assessment could be an independent predictive factor in patients with PCNSL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Ventricle contact may be associated with higher 11C methionine PET uptake in glioblastoma

PurposeVentricle contact is associated with a worse prognosis and more aggressive tumor characteristics in glioblastoma (GBM). This is hypothesized to be a result of neural stem cells located around the lateral ventricles, in the subventricular zone. 11C Methionine positron emission tomography (metPET) is an indicator for increased proliferation, as it shows uptake of methionine, an amino acid needed for protein synthesis. This study is the first to study metPET characteristics of GBM in relation to ventricle contact.MethodsA total of 12 patients with IDH wild-type GBM were included. Using MRI, the following regions were determined: primary tumor (defined as contrast enhancing lesion on T1) and peritumoral edema (defined as edema visible on FLAIR excluding the enhancement). PET parameters in these areas were extracted using PET fused with MRI imaging. Parameters extracted from the PET included maximum and mean tumor-to-normal ratio (TNRmax and TNRmean) and metabolic tumor volume (MTV).ResultsTNRmean of the primary tumor showed significantly higher values for the ventricle-contacting group compared to that for the non-contacting group (4.44 vs 2.67, p = 0.030). Other metPET parameters suggested higher values for the ventricle-contacting group, but these differences did not reach statistical significance.ConclusionGBM with ventricle contact demonstrated a higher methionine uptake and might thus have increased proliferation compared with GBM without ventricle contact. This might explain survival differences and should be considered in treatment decisions.

C-methionine-PET-guided Gamma Knife radiosurgery boost as adjuvant treatment for newly diagnosed glioblastomas

Background: The most common glial tumor is the glioblastoma, and the prognosis remains dismal despite a multimodal therapeutic approach. The role of radiosurgery for the treatment of glioblastomas has been evaluated in several studies with some benefit at the recurrent stage. We evaluate the results of the protocol administered at the Gamma Knife unit administering radiosurgery as a boost to metabolic active parts of the tumor after the patient had completed traditional external beam radiotherapy (XBRT) as part of the Stupp protocol for high-grade gliomas.Methods: This is a retrospective analysis of seven patients with newly diagnosed glioblastomas who were treated with Gamma Knife radiosurgery as a boost after receiving XBRT as part of the Stupp protocol. The target of radiation was determined according to the findings of the C-methionine PET scan in relation to magnetic resonance images. The primary end point of this study was to determine the progression-free survival (PFS) from the time of diagnosis.Results: The median age of patients was 48.8 years and the mean Karnofsky performance score was 92.8%. The median PFS was 12.4 months. No radiation adverse effects were documented.Conclusion: Stereotactic radiosurgery is safe to use in the upfront treatment for these patients and appears to have a beneficial role in improving the PFS. This beneficial role seems to be conditioned not only by the time the treatment is administered but also where the radiation dose is targeted to.

First Turkey Experience of 11C-Methionine PET in Multiple Myeloma

First Turkey Experience of 11C-Methionine PET in Multiple Myeloma

RONC-20. RECURRENT HIGH-GRADE ASTROBLASTOMA TREATED WITH STEREOTACTIC RADIOTHERAPY

INTRODUCTIONAstroblastoma is a rare, mostly supratentorial glial tumor, occurring predominantly in children and young adults. However, treatment strategies have not yet been established for this rare disease.CASE PRESENTATIONA 6-year-old male presented with headache and nausea. CT and MR imaging revealed a left frontal mass lesion with slight edema and macrocalcifications. Gross tumor resection was performed. Histological examination found neoplastic cells with astroblastic characteristics, and a striking perivascular array of pseudorosettes. The final diagnosis was high-grade astroblastoma. MR imaging 13 months after surgery suggested local recurrence and enlargement was found 3 months later. Stereotactic radiotherapy (SRT) was performed. MR imaging after SRT showed enhanced cyst formation around the tumor bed, suggesting tumor recurrence. However, 11C-methionine PET revealed radiation necrosis. The last follow-up MR imaging 15 months after SRT showed no further recurrence.CONCLUSIONAstroblastoma is rare, so no optimal management is known. SRT may be effective to treat recurrent astroblastomas. 11C-methionine PET/CT is useful for the differentiation from radiation necrosis.

ACT-07 Clinical Trials of 11C-Methionine PET for brain tumors

Background: Although 11C-Methionine (MET) PET has widely used, 11C-MET tracer has not been approved in Japan. We conducted multi-center prospective clinical trials using MET for drug approval in diagnosis of brain tumors[Methods] Two trials using 11C-MET PET were performed in Hokkaido University, Osaka University and Fukushima Medical University; 1) Diagnostic accuracy in differentiating tumor recurrence from radiation injury after radiotherapy in brain tumors, 2) The diagnostic efficacy in newly-diagnosed gliomas. 1) The patients with suspected brain tumor recurrence underwent MET and 18F-Fluorodeoxyglucose (FDG) PET. When the target lesion showed MET and/or FDG uptake, the patients underwent target resection for pathological confirmation. Positive prediction values of each tracer uptake were assessed as primary outcome measure, and the sensitivities and specificities of each PET exams were also assessed. 2) The patients with suspected gliomas underwent MET PET. Tissue samplings were performed from MET uptake lesions without contrast-enhancement on MRI in each patient, and evaluated the existence of tumor cells. Diagnostic additional values of MET PET on contrast-enhanced MRI was also investigated. Safety of MET PET was also assessed in each trial.[Result] 1) 57 cases were investigated. 38 cases underwent surgery and 32 cases (84%) were confirmed tumor recurrence histopathologically. MET and FDG uptake in 32 recurrence cases were 100% and 50%, respectively. Sensitivities and specificities of tumor recurrence were 84% and 89% in MET, and 100% and 56% in FDG. 2) 53 glioma cases were enrolled. Viable tumor cells were proven in 98% in MET uptake lesion without contrast-enhancement. In 42 out of 53 cases (78%), MET PET depicted tumor area beyond the contrast-enhancement area on MRI. No severe adverse events were observed in both trials. [Conclusions] MET PET were effective in diagnosis of brain tumors, and safety of MET was demonstrated.

NI-19 Use of 11C-methionine PET for decision of discontinuation of adjuvant chemotherapy with temozolomide

Background: The aim was to clarify whether positron emission tomography with 11C-methyl-L-methionine (met-PET) is useful to decide on discontinuation of TMZ-adjuvant therapy in patients with residual diffuse astrocytic tumor. Methods: Subjects were 44 patients with residual tumor comprising 17 with IDH1-mutant diffuse astrocytoma (DA), 13 with IDH1-mutant anaplastic astrocytoma (AA), and 14 with IDH1-wild glioblastoma (GB). All patients received TMZ-adjuvant chemotherapy (median, 12 courses), and whether to discontinue or continue TMZ-adjuvant chemotherapy was decided on the basis of the tumor-to-normal ratio in standardized uptake value from met-PET (T/N); patients with T/N < 1.6 immediately discontinued TMZ, and patients with T/N > 1.6 were either to continued or discontinued TMZ. Progression-free survival (PFS) was compared between patients with T/N > 1.6 and T/N < 1.6 in each tumor type. Median observation period was 434 days after met-PET scanning. Results: The number of patient who underwent recurrence was 10 in DA, 7 in AA, and 11 in GB. All patients showing T/N > 1.6 underwent tumor recurrence. PFS was significantly longer in patients with T/N < 1.6 than T/N > 1.6 in DA and AA (p < 0.01 in both types), but was no significant difference between 2 groups in GB (p = 0.06). Sixteen of 17 patients (94%) in DA and AA showed recurrence from residual tumor, whereas 4 of 11 patients (36%) in GB showed recurrent tumor at remote regions which were different from residual tumor. Conclusions: The present study suggested that met-PET is beneficial to decide to discontinue adjuvant chemotherapy with TMZ in patients with residual tumors of DA and AA, but not useful for patients with GB. Reasons for unsuccessful results in GB might have been small sample size, failure of establishing the cut off value in T/N, recurrences at remote regions where not be assessed by met-PET.

Photopenic Defects in Gliomas With Amino-Acid PET and Relative Prognostic Value: A Multicentric 11C-Methionine and 18F-FDOPA PET Experience.

The aim is to explore the concept of photopenic defects in newly diagnosed glioma patients with the 2 widely used C-MET and F-FDOPA PET amino acid tracers. Thirty-two C-MET and 26 F-FDOPA PET scans with amino acid PET-negative gliomas were selected in this European multicentric study. Of these gliomas, 16 C-MET and 10 F-FDOPA PET scans with photopenic defects were identified, exhibiting lower mean tumor-to-background ratio as compared with isometabolic gliomas (P < 0.001). Gliomas with photopenic defects had no different progression-free survival than isometabolic gliomas in the whole population (P = 0.40), but shorter progression-free survival in the subgroup of World Health Organization grade II IDH-mutant astrocytomas (35 vs 68 months; P = 0.047).

MON-LB58 The Use of 11C Methionine PET CT In Localization of ACTH Dependent Cushing’s Disease

Background and objective: Hypercortisolism is the hall mark of ACTH Cushing’s syndrome, which is a benign ACTH secreting tumor resulting in high morbidity and mortality. The diagnosis is based on an elevated serum ACTH, elevated 24h urinary cortisol or a non-suppressible ACTH after dexamethasone suppression test. Confirmation of ACTH hypersecretion is followed by localization of the adenoma which can be pituitary in origin or peripheral. Dynamic MRI of the pituitary gland is the gold standard for diagnosis of pituitary tumors, and contrast enhanced CT scan is the gold standard for ectopic lesions which are usually lung tumors. The localization of the lesion is often a challenge because conventional MRI fail to show pituitary lesions and sometimes requiring inferior petrosal sinus sampling to confirm pituitary origin. Transsphenoidal surgery is the treatment of choice for Cushing’s disease, even without MRI evidence of pituitary tumors, if pituitary origin is confirmed by inferior petrosal sinus sampling. This causes increase in the incidence of treatment failure and complications. Thus, the diagnosis of Cushing’s disease urges exploring new diagnostic modalities. In our study we test the sensitivity of 11C methionine PET CT together with dynamic pituitary MRI in localization of ACTH dependent Cushing’s disease. Materials and methods This is an interventional, prospective study, forty-one subjects: newly diagnosed ACTH dependent Cushing’s Syndrome (n=29). (indicated by non-suppressible ACTH on dexamethasone suppression test) or persistent hypercortisolism following transsphenoidal surgery (n=12). 11C methionine PET CT was done in all cases in addition to dynamic pituitary MRI. All patients underwent 11 C-methionine PET-CT in addition to dynamic pituitary MRI This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging.Inclusion Criteria:• Aged 18 years old or over• Patient with a diagnosed Cushing’s disease confirmed by non-suppressible ACTH on dexamethasone suppression test.• Patient with persistent ACTH dependent Cushing’s disease following transsphenoidal surgery.• Patient not enrolled in other interventional studies.Exclusion Criteria:• Contraindication to MRI• Pregnant woman, breastfeeding RESULTS: Patients with newly diagnosed ACTH dependent Cushing: 24 out of 29 of the cases showed adenoma on dynamic MRI of the pituitary; 5 out of 29 cases failed to showed any lesions on dynamic MRI of the pituitary; Inferior petrosal sampling was done and confirmed pituitary origin in 4 out of 5 and 1 out of 5 was found to have ectopic ACTH secretion. In patients with persistent hypercortisolism following transsphenoidal surgery; 3 out of 12 of the cases showed adenoma on dynamic MRI of the pituitary and 7 out of 12 cases failed to showed any lesions on dynamic MRI of the pituitary and inferior petrosal sampling was done and confirmed pituitary origin in all 12 cases. All 41 cases underwent 11C methionine PET CT scan; 39 patients showed tracer uptake on 11c methionine PET CT scan in the pituitary area, 36 of which had unilateral asymmetrical tracer uptake. All 40 subjects with suspected pituitary lesions were confirmed to be of pituitary origin by histopathological examination of biopsies taken intraoperatively. CONCLUSIONS 11C methionine PET CT has proven to be of very high sensitivity in detecting ACTH secreting adenomas, further studies should be done on a larger scale as this modality can address the pitfalls in localization of ACTH secreting lesions.

The role of 11C-methionine PET in patients with negative diffusion-weighted magnetic resonance imaging: correlation with histology and molecular biomarkers in operated gliomas.

To compare 11C-methionine (11C-METH) PET with diffusion-weighted MRI (DWI-MRI) diagnostic accuracy and prognostic value in patients with glioma candidate to neurosurgery. We collected and analyzed data from 124 consecutive patients (n = 124) investigated during preoperative work-up. Both visual and semiquantitative parameters were utilized for image analysis. The reference standard was based on histopathology. The median follow-up was 14.3 months. Overall, 47 high-grade gliomas (HGG) and 77 low-grade gliomas (LGG) were diagnosed. On visual assessment, sensitivity and specificity for differentiating HGG from LGG were 80.8 and 59.7% for DWI-MRI, versus 95.7 and 41.5% for 11C-METH PET, respectively. On semiquantitative analysis, the sensitivity, specificity, and area under the curve were 78.7, 71.4, and 80.4% for SUVmax, 78.7, 70.1, and 81.1% for SUVratio, and 74.5, 61, and 76.7% for MTB (metabolic tumor burden), respectively. In patients with negative DWI-MRI and IDH-wild type, SUVmax and SUVratio were higher compared to IDH-mutated (P = 0.025 and P = 0.01, respectively). In LGG, patients with 1p/19q codeletion showed higher SUVmax (P = 0.044). In all patients with negative DWI-MRI, median PFS was longer for SUVmax <3.9 (median not reached vs 34.2 months, P = 0.004), SUVratio <2.3 (median not reached vs 21.5 months, P < 0.001), and MTB <3.1 (median not reached vs 45.7 months, P = 0.05). In LGG patients with negative DWI-MRI, only SUVratio <2.3 and MTB <3.1 were associated with longer PFS (P = 0.016 and P = 0.024, respectively). C-METH PET was found highly sensitive for glioma differentiation and molecular characterization. In DWI-negative patients, PET parameters correlated with molecular profile were associated with clinical outcome.

The association between 11C-methionine uptake, IDH gene mutation, and MGMT promoter methylation in patients with grade II and III gliomas

To evaluate the association between 11C-methionine positron-emission tomography (11C-methionine PET) findings, isocitrate dehydrogenase (IDH) gene mutation, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in patients with grade II and III gliomas. Data were collected from 40 patients with grade II and III gliomas who underwent both magnetic resonance imaging (MRI) and 11C-methionine PET as part of their pre-surgical examination. IDH mutation was examined via DNA sequencing, and MGMT promoter methylation via quantitative methylation-specific polymerase chain reaction (PCR). A threshold of MGMT promoter methylation of 1% was significantly associated with tumour/normal tissue (T/N) ratio. The T/N ratio in samples with MGMT promoter methylation ≥1% was higher than that in samples with MGMT promoter methylation <1%, and the difference was statistically significant (p=0.011). Reliable prediction of MGMT promoter methylation (<1% versus ≥1%) was possible using the T/N ratio under the receiver operator characteristic (ROC) curve with a sensitivity and specificity of 75% each (cut-off value=1.6: p=0.0226, area under the ROC curve [AUC]=0.76172). Conversely, the T/N ratio had no association with IDH mutation (p=0.6). The ROC curve revealed no reliable prediction of IDH mutation using the T/N ratio (p=0.606, AUC=0.60577). 11C-methionine PET parameters can predict MGMT promoter methylation but not IDH mutation status. 11C-methionine uptake may have limited potential to reflect DNA methylation processes in grade II and III gliomas.

11C-Methionine PET Identifies Astroglia Involvement in Heart-Brain Inflammation Networking After Acute Myocardial Infarction.

Acute myocardial infarction (MI) triggers a local and systemic inflammatory response. We recently showed microglia involvement using translocator protein imaging. Here, we evaluated whether 11C-methionine provides further insight into heart-brain inflammation networking. Methods: Male C57BL/6 mice underwent permanent coronary artery ligation followed by 11C-methionine PET at 3 and 7 d (n = 3). In subgroups, leukocyte homing was blocked by integrin antibodies (n = 5). The cellular substrate for PET signal was identified using brain section immunostaining. Results:11C-methionine uptake (percentage injected dose/cm3) peaked in the MI region on day 3 (5.9 ± 0.9 vs. 2.4 ± 0.5), decreasing to the control level by day 7 (4.3 ± 0.6). Brain uptake was proportional to cardiac uptake (r = 0.47, P < 0.05), peaking also on day 3 (2.9 ± 0.4 vs. 2.4 ± 0.3) and returning to baseline on day 7 (2.3 ± 0.4). Integrin blockade reduced uptake at every time point. Immunostaining on day 3 revealed colocalization of the l-type amino acid transporter, with glial fibrillary acidic protein-positive astrocytes but not CD68-positive microglia. Conclusion: PET imaging with 11C-methionine specifically identifies an astrocyte component, enabling further dissection of the heart-brain axis in post-MI inflammation.