11C-methionine PET Research Articles

P13.01.A 11C-METHIONIN PET FOR RADIOTHERAPY TREATMENT PLANNING IN PATIENTS WITH RAPID EARLY PROGRESSION AFTER GLIOBLASTOMA SURGERY: PROSPECTIVE PHASE II TRIAL

Abstract BACKGROUND Radiotherapy (RT) is a standard treatment for nearly all glioblastoma patients following initial surgery. Few retrospective studies indicate negative prognostic instances of progression during the planning magnetic resonance (MR) (up to 1 week before initiating RT), termed Rapid Early Progression (REP). The optimal RT management for REP patients remains uncertain. The objective of this prospective phase II trial (NCT05608395) is to assess impact of 11C-Methionine PET used for RT planning in REP glioblastoma patients. It is one of the first prospective clinical interventional trials focused on this specific cohort of patients. MATERIAL AND METHODS We enrolled glioblastoma, IDHwt, or Astrocytoma, IDHmt, WHO grade IV patients, who developed REP characterized by 1) increase in postoperative residuum by ≥ 25%, 2) appearance of new contras enhancing lesion, 3) unequivocal progression of the unresected satelite. Patients received treatment based on the Stupp or Perry protocol. Treatment response was evaluated using RANO criteria. RT target volumes were delineated as follows: Gross tumor volume included tumor cavity, enhancing lesion and 11C-MET PET (1.3 tumor-to-background ratio). The clinical target volume was GTV plus a modified 2cm margin reflecting surrounding organs at risk. Volumetric analyses of different radiotherapy target volume were performed using EclipseTM software including patterns of failure. RESULTS During 12/2020 - 12/2023, total of 31 patients were enrolled (16 treated via abbreviated RT course); median age 60 years, ECOG 0-1 in 28 patients, median follow up 20 months. No effect of 11C-MET PET - based radiotherapy treatment planning of GBM patients with REP was observed on PFS (median 3.4 months comparing to 4.9 in historical control cohort) and OS (12.3 months comparing to 15.7 months). Median MET volume was 7.3cm3 (43% of MRI volume), MET avidity was presented in 7 patients et least 1cm beyond MRI volume. Central recurrence was presented in 87% patients. CONCLUSION The optimal treatment of patients with REP is unknown and needs to be studied in more details including dose escalation studies with reduced target margins potentialy directed also by aminoacid PET examination. Adjustment of target radiotherapy volumes using 11C-MET PET did not lead to improved PFS or OS. Supported by NU20-03-00148.

Predicting Isocitrate Dehydrogenase Status in Non-Contrast-Enhanced Adult-Type Astrocytic Tumors Using Diffusion Tensor Imaging and 11C-Methionine, 11C-Choline, and 18F-Fluorodeoxyglucose PET.

We aimed to differentiate the isocitrate dehydrogenase (IDH) status among non-enhanced astrocytic tumors using preoperative MRI and PET. We analyzed 82 patients with non-contrast-enhanced, diffuse, supratentorial astrocytic tumors (IDH mutant [IDH-mut], 55 patients; IDH-wildtype [IDH-wt], 27 patients) who underwent MRI and PET between May 2012 and December 2022. We calculated the fractional anisotropy (FA) and mean diffusivity (MD) values using diffusion tensor imaging. We evaluated the tumor/normal brain uptake (T/N) ratios using 11C-methionine, 11C-choline, and 18F-fluorodeoxyglucose PET; extracted the parameters with significant differences in distinguishing the IDH status; and verified their diagnostic accuracy. Patients with astrocytomas were significantly younger than those with glioblastomas. The following MRI findings were significant predictors of IDH-wt instead of IDH-mut: thalamus invasion, contralateral cerebral hemisphere invasion, location adjacent to the ventricular walls, higher FA value, and lower MD value. The T/N ratio for all tracers was significantly higher for IDH-wt than for IDH-mut. In a composite diagnosis based on nine parameters, including age, 84.4% of cases with 0-4 points were of IDH-mut; conversely, 100% of cases with 6-9 points were of IDH-wt. Composite diagnosis using all parameters, including MRI and PET findings with significant differences, may help guide treatment decisions for early-stage gliomas.

Clinical decision-making based on 11C-methionine PET in recurrent Cushing's disease with equivocal MRI findings.

Diagnosis and accurate localization of recurrent tumors in Cushing's disease (CD) are challenging, especially after multiple transsphenoidal surgeries (TSSs) or radiosurgery. Even experts face difficulties in detecting these recurrent tumors, and a favorable surgical outcome is not guaranteed. In this report, the authors aimed to determine the usefulness of 11C-methionine positron emission tomography (MET-PET) for evaluating patients with recurrent CD with inconclusive magnetic resonance imaging (MRI) lesions and to develop a treatment protocol for these cases. In this retrospective study of patients with recurrent CD in the period between April 2018 and December 2022, the authors assessed the usefulness of MET-PET in determining whether equivocal MRI findings were recurrent tumors or postsurgical cavities and deciding further treatment options. All patients had undergone at least one TSS, and most had undergone multiple TSSs and had pathologically confirmed corticotroph tumors with hypercortisolemia. Overall, 15 patients with recurrent CD (10 females and 5 males) were included, all of whom had undergone MET-PET. All patients had been subjected to multiple treatments, including TSSs or radiosurgeries. Their MRI scans demonstrated less-enhanced lesions that were not confirmed as recurrences even with cutting-edge MRI because they could not be distinguished from postsurgical changes with confidence. MET uptake was positive in 8 patients (9 examinations) and negative in 7. Following MET-PET, repeat TSS was performed in 5 patients. Corticotroph tumors were identified in all 5 patients, even though one of them had negative MET uptake. The MET uptake precisely identified a tumor location on the opposite side of the MRI-suspected lesion in 2 patients. Meanwhile, patients with negative uptake and mild hypercortisolism were only observed. Nonsurgical options were also used in other patients: temozolomide (TMZ) was administered in 2 patients owing to a prior history of multiple TSSs and radiosurgery and the drug-resistant nature of the disease. TMZ was highly effective in these patients; their Cushing's symptoms ameliorated, and their adrenocorticotropic hormone and cortisol levels continued to decline. Interestingly, MET uptake disappeared following TMZ treatment. MET-PET is extremely useful for confirming equivocal lesions on MRI in patients with recurrent CD and for deciding further treatment options. The authors propose a novel protocol based on MET-PET results for treating patients with relapsing CD in whom the recurrent tumors cannot be confirmed with MRI.

NIMG-08. ANALYSIS OF11C-METHIONINE PET UPTAKE AND PROGNOSIS IN LOWER GRADE GLIOMAS

Abstract PURPOSE The 2021 WHO Classification of Tumors of the Central Nervous System incorporates molecular alterations into the classification system, with the goal of creating more homogenous disease categories with greater prognostic value. This study aimed to assess the correlation between 11C-methionine uptake, molecular features and prognosis in newly diagnosed lower-grade gliomas (LGGs). METHODS 93 newly diagnosed LGG patients (Grade 2: 39 patients, Grade 3: 54 patients) who underwent surgery at Tokyo Medical and Dental University Hospital from 2000 to 2020 and imaged preoperatively using 11C-methionine PET were retrospectively included in this study. These patients were re-classified according to the 2021 WHO classification. The tumor-to-normal ratio (T/N) of 11C-methionine uptake was calculated by dividing the mean standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain. RESULTS 44 out of 93 gliomas were IDH wild-type tumors and re-classified as glioblastoma or pediatric-type gliomas according to the 2021 WHO classification and therefore excluded from the analysis. Remaining 49 LGGs were re-classified in two types- Oligodendrogliomas, IDH-mutant and 1p/19q- codeleted (n=25), and Astrocytomas, IDH-mutant (n=24)- following the indications provided by the 2021 WHO classification. The median T/N ratio in Oligodendrogliomas, IDH-mutant and 1p/19q- codeleted were 1.83 in grade 2 and 2.83 in grade 3, which were significantly higher than those in Astrocytoma, IDH-mutant (grade2: 1.38, grade3:1.62). Kaplan–Meier survival analysis revealed that Oligodendroglioma, IDH-mutant and 1p/19q- codeleted had significantly better outcomes regardless of WHO grade. CONCLUSION The results indicated that LGG categories reclassified with molecular classification correlate with the T/N ratio of methionine uptake and the prognosis.

Real-world experience with 11C-methionine PET co-registered with MRI in the management of acromegaly - Insights from a single reference centre 12 year observation

Real-world experience with 11C-methionine PET co-registered with MRI in the management of acromegaly - Insights from a single reference centre 12 year observation

Use of osilodrostat alongside 11C-Methionine PET CT in pituitary-dependent Cushing's disease may improve radiological detection and lead to better outcomes

Use of osilodrostat alongside 11C-Methionine PET CT in pituitary-dependent Cushing's disease may improve radiological detection and lead to better outcomes

The Assessment of Glioblastoma Metabolic Activity via 11C-Methionine PET and Radiomics.

Nowadays, the quantitative analysis of PET/CT data in patients with glioblastoma is not strictly standardized in the clinic and does not exclude the human factor. This study aimed to evaluate the relationship between the radiomic features of glioblastoma 11C-methionine PET images and the tumor-to-normal brain (T/N) ratio determined by radiologists in clinical routine. PET/CT data were obtained for 40 patients (mean age 55 ± 12 years; 77.5% men) with a histologically confirmed diagnosis of glioblastoma. Radiomic features were calculated for the whole brain and tumor-containing regions of interest using the RIA package for R. We redesigned the original RIA functions for GLCM and GLRLM calculation to reduce computation time significantly. Machine learning over radiomic features was applied to predict T/N with the best median correlation between the true and predicted values of 0.73 (p = 0.01). The present study showed a reproducible linear relationship between 11C-methionine PET radiomic features and a T/N indicator routinely assessed in brain tumors. Radiomics enabled utilizing texture properties of PET/CT neuroimaging that may reflect the biological activity of glioblastoma and can potentially augment the radiological assessment.

Ectopic sphenoidal ACTH-secreting adenoma revealed by 11C Methionine PET scan: case report

BackgroundEctopic ACTH pituitary adenomas (EAPA), located outside the sella turcica and deriving from cellular remnants of Rathke’s pouch are a very rare cause of Cushing’s syndrome (CS). The diagnosis is often difficult and delayed, even after comprehensive work-up. To our knowledge, we report for the first time an ectopic corticotroph tumor of the posterior wall of the sphenoid sinus, leading to false positive results of bilateral inferior petrosal sinus sampling (BIPPS) and which was finally localized by a co-registered11 C Methionine PET/MR imaging.Case presentationA 48-year-old woman was referred for a high clinical suspicion of ACTH-dependent CS. Biological testing comprising low dose dexamethasone suppression and CRH stimulation tests were indicative of pituitary Cushing’s disease, but comprehensive pituitary MRI did not reveal any pituitary adenoma. BIPSS confirmed however a central origin of ACTH secretion (central-to-peripheral ACTH ratio > 100) and revealed a significant right-to-left gradient (6.2), leading to a first right-sided exploratory hypophysectomy, that did not cure the patient. BIPSS images were reviewed and revealed preferential drainage of the left pituitary to the right petrosal sinus, leading us to a left sided exploratory hypophysectomy, which was again unsuccessful. A11 C Methionine PET/MRI was performed and revealed a hypermetabolic lesion adjacent to the posterior wall of the sphenoidal sinus. After surgical resection, this polypoid mass was identified as an ectopic ATCH-secreting pituitary adenoma expressing ACTH and T-Pit and complete remission of hypercortisolism was observed.ConclusionsIn conclusion, we report a case of ACTH-dependent Cushing’s syndrome, caused by an ectopic corticotroph adenoma located in the sphenoidal sinus, which perfectly mimicked the biological features of a classical pituitary ACTH adenoma on a comprehensive hormonal evaluation including BIPPS, and the features of a benign naso-sinusal polyp at MRI. We report for the first time a key role of11 C Methionine PET co-registered to high resolution MRI for localizing ectopic adenomas, efficiently guiding surgical removal and leading to complete remission of hypercortisolism.

11C-methionine PET imaging characteristics in children with diffuse intrinsic pontine gliomas and relationship to survival and H3 K27M mutation status.

This study aimed to describe 11C-methionine (11C-MET) PET imaging characteristics in patients with paediatric diffuse intrinsic pontine glioma (DIPG) and correlate them with survival and H3 K27M mutation status. We retrospectively analysed 98 children newly diagnosed with DIPG who underwent 11C-MET PET. PET imaging characteristics evaluated included uptake intensity, uniformity, metabolic tumour volume (MTV), and total lesion methionine uptake (TLMU). The maximum, mean, and peak of the tumour-to-background ratio (TBR), calculated as the corresponding standardised uptake values (SUV) divided by the mean reference value, were also recorded. The associations between the PET imaging characteristics and clinical outcomes in terms of progression-free survival (PFS) and overall survival (OS) and H3 K27M mutation status were assessed, respectively. In univariate analysis, imaging characteristics significantly associated with shorter PFS and OS included a higher uniformity grade, higher TBRs, larger MTV, and higher TLMU. In multivariate analysis, larger MTV at diagnosis, shorter symptom duration, and no treatment were significantly correlated with shorter PFS and OS. The PET imaging features were not correlated with H3 K27M mutation status. Although several imaging features were significantly associated with PFS and OS, only MTV, indicating the size of the active tumour, was identified as a strong independent prognostic factor.

PMON94 Collision tumor with Rathke cleft cyst and co existing Cushing's disease

Abstract Introduction - Collision tumors, i.e., co-occurring distinct histopathological lesions are rare. We present a case of a 48-year-old female present with co-existing Rathke cleft cyst (RCC) and pituitary adenoma with Cushing disease. Case - 48-year-old female presented for evaluation of an incidental sellar mass with enlarged pituitary noted on MRI brain. The patient complained of symptoms of mental fogginess, confusion, intermittent dizziness for the last 1 year. The patient had complained of easy bruising with no reported weight gain, change in facial appearance, proximal muscle weakness. MRI brain showed mildly enlarged pituitary measuring 13 mm with RCC.Past medical history was significant for recent-onset Type 2 Diabetes and Hypertension. The examination was unremarkable with no signs of Cushing's syndrome. Lab work showed elevated ACTH of 51 pg/ml (10-48) with AM cortisol level of 14.7 mcg/dl (6- 18.4). IGF-1 levels elevated at 307 ng/ml (77- 220). LH, FSH, FT4, prolactin levels were normal. Given elevated ACTH levels, further testing showed elevated midnight salivary cortisol at 0.22 and 0.239 mcg/dl (0.010-0.090), elevated 24-hour urine cortisol 141 ug/ 24 hrs. (6- 44), absence of suppression with 1 mg dexamethasone with cortisol 12.4 mcg/dl (< 1.8), ACTH 123 pg/ml (10-48) with dexamethasone levels 432 ng/dl (140- 295). Lab work was consistent with ACTH-dependent hypercortisolism. MRI pituitary showed 7.5×7.8 mm RCC.8 mg dexamethasone suppression test and CT chest, abdomen, and pelvis were performed to differentiate between ectopic Cushing's and Cushing's disease. Cortisol levels suppressed greater than 50% after 8 mg dexamethasone from baseline cortisol – 17.7 mcg/dl and ACTH 67 pg/ml to cortisol 3.4 mcg/dl and ACTH – 34 pg/ml with dexamethasone levels of 3120 ng/dl (1600–2850). CT chest abdomen, pelvis showed no evidence of bronchial carcinoid or other potential lesions. With neuroimaging findings and biochemical confirmation of Cushing's disease, the patient underwent transsphenoidal resection. Discussion – The association between RCC and pituitary adenoma was found in 0.5–1.9% cases per literature review1, co-occurrence with ACTH producing pituitary adenoma being rarer. The diagnosis of collision tumors can be challenging as the most common presentation on imaging is a cystic mass. Appropriate biochemical testing is indicated based on clinical presentation, initial laboratory testing, and level of suspicion. Elevated ACTH levels along with diabetes and hypertension led to a diagnosis of Cushing's disease in our patient with the initial presentation of an incidental RCC. The knowledge about collision tumors is important, especially in unusual presentations as in our case. References Sagan KP et al. Cushing's Syndrome in a patient with Rathke's cleft cyst and ACTH cell hyperplasia detected by 11C-Methionine PET Imaging-A Case Presentation. Front Endocrinol (Lausanne). 2020; 11: 460. Published 2020 Jul 22. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Depot somatostatin receptor ligand therapy reverses tissue thyrotoxicosis in thyrotropinomas and aids microadenoma localization via 11C-Methionine PET

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Diverse Patterns and Clinical Significance of 11C-Methionine PET in Dysembryoplastic Neuroepithelial Tumors.

Dysembryoplastic neuroepithelial tumors (DNETs) are slow-growing epilepsy-associated tumors. Low or normal 11C-methionine (MET) PET uptake helps to differentiate DNETs from other low-grade gliomas. However, diverse MET-PET uptake in DNETs has been observed. The aim of this study is to measure the clinical significance and prognostic value of MET-PET in DNET management. Retrospective review of 26 DNET patients was done. Clinical characteristics, radiologic findings, and visual and quantitative MET-PET results were analyzed. PET uptake was calculated as the tumor-to-homotopic mirror ratio (TNRm) and tumor-to-contralateral cortex ratio (TNRc). The clinical activity of the tumors at the time of PET was classified into active and quiescent groups. The surgical outcome was defined as a composite of 2 different aspects: tumor progression and/or clinical events such as seizure recurrence or tumor bleeding. Twenty-seven MET-PET examinations (20 initial MET-PET and 7 MET-PET during follow-up) were included. Clinically active tumors at the time of PET presented significantly higher values of TNRm and TNRc than quiescent tumors. High MET-PET uptake by visual grading, TNRm ≥ 1.90, and TNRc ≥ 1.85 exhibited poor prognosis for event-free survival. MET-PET uptake correlates well with the clinical behavior of DNETs at the time of PET examination. Moreover, High MET-PET uptake is closely related to seizure recurrence if tumors are not entirely resected. Efforts to achieve gross total resection should be made for DNETs with high MET-PET uptake.

11C-methionine PET aids localization of microprolactinomas in patients with intolerance or resistance to dopamine agonist therapy

PurposeTo assess the potential for 11C-methionine PET (Met-PET) coregistered with volumetric magnetic resonance imaging (Met-PET/MRCR) to inform clinical decision making in patients with poorly visualized or occult microprolactinomas and dopamine agonist intolerance or resistance.Patients and methodsThirteen patients with pituitary microprolactinomas, and who were intolerant (n = 11) or resistant (n = 2) to dopamine agonist therapy, were referred to our specialist pituitary centre for Met-PET/MRCR between 2016 and 2020. All patients had persistent hyperprolactinemia and were being considered for surgical intervention, but standard clinical MRI had shown either no visible adenoma or equivocal appearances.ResultsIn all 13 patients Met-PET/MRCR demonstrated a single focus of avid tracer uptake. This was localized either to the right or left side of the sella in 12 subjects. In one patient, who had previously undergone surgery for a left-sided adenoma, recurrent tumor was unexpectedly identified in the left cavernous sinus. Five patients underwent endoscopic transsphenoidal selective adenomectomy, with subsequent complete remission of hyperprolactinaemia and normalization of other pituitary function; three patients are awaiting surgery. In the patient with inoperable cavernous sinus disease PET-guided stereotactic radiosurgery (SRS) was performed with subsequent near-normalization of serum prolactin. Two patients elected for a further trial of medical therapy, while two declined surgery or radiotherapy and chose to remain off medical treatment.ConclusionsIn patients with dopamine agonist intolerance or resistance, and indeterminate pituitary MRI, molecular (functional) imaging with Met-PET/MRCR can allow precise localization of a microprolactinoma to facilitate selective surgical adenomectomy or SRS.

Glioblastoma Recurrence Versus Radiotherapy Injury: Combined Model of Diffusion Kurtosis Imaging and 11C-MET Using PET/MRI May Increase Accuracy of Differentiation.

To evaluate the diagnostic potential of decision-tree model of diffusion kurtosis imaging (DKI) and 11C-methionine (11C-MET) PET, for the differentiation of radiotherapy (RT) injury from glioblastoma recurrence. Eighty-six glioblastoma cases with suspected lesions after RT were retrospectively enrolled. Based on histopathology or follow-up, 48 patients were diagnosed with local glioblastoma recurrence, and 38 patients had RT injury between April 2014 and December 2019. All the patients underwent PET/MRI examinations. Multiple parameters were derived based on the ratio of tumor to normal control (TNR), including SUVmax and SUVmean, mean value of kurtosis and diffusivity (MK, MD) from DKI, and histogram parameters. The diagnostic models were established by decision trees. Receiver operating characteristic analysis was used for evaluating the diagnostic accuracy of each independent parameter and all the diagnostic models. The intercluster correlations of DKI, PET, and texture parameters were relatively weak, whereas the intracluster correlations were strong. Compared with models of DKI alone (sensitivity =1.00, specificity = 0.70, area under the curve [AUC] = 0.85) and PET alone (sensitivity = 0.83, specificity = 0.90, AUC = 0.89), the combined model demonstrated the best diagnostic accuracy (sensitivity = 1.00, specificity = 0.90, AUC = 0.95). Diffusion kurtosis imaging, 11C-MET PET, and histogram parameters provide complementary information about tissue. The decision-tree model combined with these parameters has the potential to further increase diagnostic accuracy for the discrimination between RT injury and glioblastoma recurrence over the standard Response Assessment in Neuro-Oncology criteria. 11C-MET PET/MRI may thus contribute to the management of glioblastoma patients with suspected lesions after RT.

Pituitary MRI in Cushing's disease - an update.

Pituitary MRI is essential in the diagnosis of ACTH-dependent Cushing's syndrome, but its results are inconsistent. The demonstration of a sellar image compatible with the diagnosis of corticotropinoma varies from 40% to 90%, depending on the centre where the imaging is performed. In fact, the expertise of the neuroradiologist, use of a Tesla 3.0 MRI and choice of sequences are fundamental. The T2 and 3D gradient echo sequences after gadolinium injection are the most informative and today allow the detection of macro- and microadenomas in almost all cases. The diagnosis of numerous picoadenomas (<3-4 mm) is more challenging. The 2D and 3D spin echo or delayed T1 SE or FLAIR sequences after gadolinium can be used as a complement or to confirm a suspicious image. Characterization of corticotropinomas remains problematic. However, the correct assessment of so-called incidentalomas by recognizing artifacts, anatomical variants and frequent Rathke's cleft cysts eliminates around 90% of the incidentalomas that mimic pituitary adenomas, as repetitively reported in the literature. For the time being, there is reason to believe that hybrid imaging combining PET and MRI such as 11C-methionine PET coregistered with volumetric MRI will solve the diagnosis of corticotropinomas in the near future.

Correlation of Intraoperative 5-ALA-Induced Fluorescence Intensity and Preoperative 11C-Methionine PET Uptake in Glioma Surgery.

Simple SummaryIn 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.

344 Comparison of Magnetic Resonance Relaxometry and Apparent Diffusion Coefficient for Tissue Cell Density Quantification in Glioma Imaging: Exploratory Study via 11C-methionine PET and Validation via Stereotactic Tissue Sampling

INTRODUCTION: Visualization of non-contrast-enhancing tumor lesions in glioma is one of the most crucial yet challenging issues for patients with this pathology. METHODS: Participants comprised of patients with low- or high-grade glioma. Correlation between T1-, T2-relaxation time, ADC, and 11C-methionine uptake as measured by positron emission tomography was investigated, followed by comparing T1-, T2-relaxation time, ADC with tumor cell density as measured by stereotactic image-guided tissue sampling. MR relaxometry was achieved by converting Magnetization Prepared Rapid Gradient Echo (MP2RAGE) images and multi-echo T2-weighted images via Bayesian inference modeling. RESULTS: T1-relaxation time &gt;1850 ms but &lt;3200 ms or T2-relaxation time &gt;115 ms, but &lt;225 ms under 3T were indicative of high 11C-methionine uptake. Stereotactic tissue sampling study confirmed that only the T1-relaxation time of 1850-3200 ms was significantly indicative of higher tumor cell density (p = 0.02). ADC was unable to show a significant correlation with 11C-methionine uptake or with tumor cell density. Synthetic tumor load images were successfully reconstructed using T1- and T2-relaxation mapping. CONCLUSION: T1-relaxation time correlated well with tumor cell density in glioma tissues, while neither T2-relaxation time nor ADC showed significant correlation. The ideal ranges for identifying high tumor load tissues was 1850-3200 ms for T1-relaxation time measured at 3 T.

Prognostic value of 11C-methionine volume-based PET parameters in IDH wild type glioblastoma.

11C-Methionine (11C-MET) PET prognostication of isocitrate dehydrogenase (IDH) wild type glioblastomas is inadequate as conventional parameters such as standardized uptake value (SUV) do not adequately reflect tumor heterogeneity. We retrospectively evaluated whether volume-based parameters such as metabolic tumor volume (MTV) and total lesion methionine metabolism (TLMM) outperformed SUV for survival correlation in patients with IDH wild type glioblastomas. Thirteen IDH wild type glioblastoma patients underwent preoperative 11C-MET PET. Both SUV-based parameters and volume-based parameters were calculated for each lesion. Kaplan-Meier curves with log-rank testing and Cox regression analysis were used for correlation between PET parameters and overall survival. Median overall survival for the entire cohort was 393 days. MTV (HR 1.136, p = 0.007) and TLMM (HR 1.022, p = 0.030) were inversely correlated with overall survival. SUV-based 11C-MET PET parameters did not show a correlation with survival. In a paired analysis with other clinical parameters including age and radiotherapy dose, MTV and TLMM were found to be independent factors. MTV and TLMM, and not SUV, significantly correlate with overall survival in patients with IDH wild type glioblastomas. The incorporation of volume-based 11C-MET PET parameters may lead to a better outcome prediction for this heterogeneous patient population.

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

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

STMO-3 Mid- to long-term outcome of supratotal resection of IDH1 wild-type glioblastoma based on 11C-methionine PET: a retrospective, single-center study

PurposeMid- to long-term outcome in glioblastoma (GBM) patients following supratotal resection (SupTR), involving complete resection both of contrast-enhancing enhanced (CE) tumors and areas of methionine (Met) uptake on 11C-Met positron emission tomography (Met-PET), are not clarified.MethodsA retrospective, single-center review was performed in newly diagnosed, IDH1 wild-type GBM patients, comparing SupTR with gross total resection (GTR), in which only CE tumor tissue was completely resected. Only patients who were operated on until November 2019 were included for evaluation of mid- to long-term outcome. Following resection, all patients underwent standard radiotherapy and temozolomide treatment, and were followed for progression-free survival (PFS) and overall survival (OS).ResultsAmong 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 PFS in the GTR and SupTR groups was 8.8 months (95% confidence interval [CI], 5.2–14.9) and 27.8 months (95% CI, 6.0-not estimable) respectively (p=0.08 by log-rank test). Median OS was 17.7 months (95% CI, 14.2–35.1) in GTR and not reached (95% CI, 30.5-not estimable) in SupTR, respectively; this difference was statistically significant (p=0.03 by log-rank test). No postoperative neurocognitive impairment was observed in SupTR patients.ConclusionCompared to GTR alone, SupTR strategy with aggressive resection of both CE tumors and Met uptake area in GBM patients under awake craniotomy with functional preservation results in a survival benefit associated with better local control.