The pituitary gland has the fourth highest physiologic avidity of [68 Ga]-DOTATATE. In order to guide our understanding of [68 Ga]-DOTATATE PET in clinical contexts, accurate characterization of the normal pituitary gland is first required. This study aimed to characterize the normal pituitary gland using dedicated brain [68 Ga]-DOTATATE PET/MRI as a function of age and sex. A total of 95 patients with a normal pituitary gland underwent brain [68 Ga]-DOTATATE PET examinations for the purpose of diagnosing CNS SSTR2 positive tumors (mean age: 58.9, 73

BACKGROUND AND PURPOSE:While contrast-enhanced MR imaging is the criterion standard in meningioma diagnosis and treatment response assessment, gallium 68Ga-DOTATATE PET/MR imaging has increasingly demonstrated utility in meningioma diagnosis and management. Integrating 68Ga-DOTATATE PET/MR imaging in postsurgical radiation planning reduces the planning target volume and organ-at-risk dose. However, 68Ga-DOTATATE PET/MR imaging is not widely implemented in clinical practice due to higher perceived costs. Our study analyzes the cost-effectiveness of 68Ga-DOTATATE PET/MR imaging for postresection radiation therapy planning in patients with intermediate-risk meningioma. MATERIALS AND METHODS:We developed a decision-analytical model based on both recommended guidelines on meningioma management and our institutional experience. Markov models were implemented to estimate quality-adjusted life-years (QALY). Cost-effectiveness analyses with willingness-to-pay thresholds of $50,000/QALY and $100,000/QALY were performed from a societal perspective. Sensitivity analyses were conducted to validate the results. Model input values were based on published literature. RESULTS:The cost-effectiveness results demonstrated that 68Ga-DOTATATE PET/MR imaging yields higher QALY (5.47 versus 5.05) at a higher cost ($404,260 versus $395,535) compared with MR imaging alone. The incremental cost-effectiveness ratio analysis determined that 68Ga-DOTATATE PET/MR imaging is cost-effective at a willingness to pay of $50,000/QALY and $100,000/QALY. Furthermore, sensitivity analyses showed that 68Ga-DOTATATE PET/MR imaging is cost-effective at $50,000/QALY ($100,000/QALY) for specificity and sensitivity values above 76% (58%) and 53% (44%), respectively. CONCLUSIONS:68Ga-DOTATATE PET/MR imaging as an adjunct imaging technique is cost-effective in postoperative treatment planning in patients with meningiomas. Most important, the model results show that the sensitivity and specificity cost-effective thresholds of 68Ga-DOTATATE PET/MR imaging could be attained in clinical practice.

Purpose: Meningiomas are the most common primary intracranial neoplasms. While MRI remains the gold standard for the evaluation of meningiomas, it has significant limitations, including limited sensitivity and specificity for infiltrative or "en plaque" lesions, presence of osseous or parenchymal invasion, and in the context of postsurgical and postradiation change.1 Meningiomas overexpress SSTR2. [68Ga]DOTATATE is a PET radiotracer that binds to somatostatin receptor 2 (SSTR2) with high affinity.2,3 [68Ga]DOTATATE PET/CT and PET/MR have previously demonstrated substantial clinical benefit compared with MRI-alone.4–7 Previous [68Ga]DOTATATE PET/CT and PET/MR studies in patients with meningiomas have demonstrated no significant between WHO grade and standardized uptake value (SUV) or SUV ratio of lesion relative to superior sagittal sinus SUV, respectively.3,5 Furthermore, prior [68Ga]DOTATATE PET/CT and PET/MR studies in patients with meningiomas focused primarily on inter-subject variability and range of SUV,8 with the assumption that all lesions within the same subject exhibit similar behavior. It is common for patients to present with multiple meningiomas; patients also develop new lesions posttreatment, both in the resection/radiation bed as well as at discontiguous disease sites. The degree of intra-subject heterogeneity with respect to [68Ga]DOTATATE PET SUV is unknown. The purpose of our study was to assess the intra-subject heterogeneity of lesion SUV in patients with >5 meningiomas and evaluate the effect of WHO Grade on meningioma SUV and SUVR.

Although liver transplant is traditionally only performed for hepatocellular carcinoma (HCC), the last decade has seen a resurgence in its use for non-HCC malignancies, likely due to improvements in neoadjuvant treatment regimens and the establishment of well-defined eligibility criteria. Given promising survival results, patients with perihilar cholangiocarcinoma, neuroendocrine liver metastases, and hepatic hemangioendothelioma are eligible to receive Model for End-Stage Liver Disease (MELD) exception points for tumors that meet well-defined criteria. Patients with additional tumors such as colorectal cancer liver metastases, intrahepatic cholangiocarcinoma, and hepatocellular cholangiocarcinoma may undergo transplant at specialized centers with well-defined protocols, although these patients are not yet eligible for MELD exception. Transplant eligibility criteria commonly incorporate imaging findings; however, because of the relatively novel and evolving nature of liver transplant for non-HCC malignancies, radiologists may be unaware of relevant criteria or the implications of their imaging interpretations. Knowledge of the allocation process, previous studies, and liver transplant selection criteria facilitates radiologists' active participation in multidisciplinary discussion, leading to better and more equitable care for transplant candidates with non-HCC malignancy. This review provides an overview of transplant allocation and selection criteria in patients with non-HCC malignancy, with an emphasis on imaging features and the role of the radiologist.

Abstract BACKGROUND Current postoperative management recommendations for meningioma lack Level 1 evidence. NRG-0539 (NCT00895622) treated recurrent WHO-1 and newly diagnosed and completely resected (by postoperative MRI) WHO-2 meningiomas with postoperative fractionated radiotherapy to 54 Gy, but 3 year PFS remained below 60%. MRI, the standard of care (SOC) for meningioma radiotherapy planning, lacks sensitivity for postoperative small volume disease and osseous or parenchymal invasion. More sensitive and specific imaging biomarkers are needed to improve RT guidance and thereby clinical outcomes in meningioma. [68Ga]-DOTATATE is a PET radiotracer targeting somatostatin receptor 2 (SSTR2), a highly sensitive and specific meningioma biomarker. We developed a dedicated DOTATATE brain PET/MRI protocol allowing meningioma differentiation from post-treatment change, using SUV analysis and Patlak modeling. Our prospective observational trial (NCT04081701) has imaged over 90 patients with meningioma. This IRB-approved study evaluated PFS in patients with WHO-2 tumors who did not achieve GTR by [68Ga]-DOTATATE PET/MRI, managed with PET/MR guided RT, hypothesizing that the PFS of patients with STR by PET/MRI managed with PET/MR guided RT would be higher than for comparable patients enrolled on NRG 0539. METHODS 92 patients with SSTR2-positive brain neoplasms were enrolled between 9/2019 and 5/2022 and imaged according to our previously published protocol. 7 patients met inclusion criteria (WHO-2 meningioma; postoperative PET/MR with residual activity) who underwent PET/MR-guided RT, followed with SOC MRI. Kaplan-Meier survival analysis was performed. RESULTS 5/7 subjects (71%) were women; the mean age was 50.7 years. MRI follow-up data were available for a mean of 18.7 months (range: 16-24 months). All patients remain progression-free at this time; Kaplan-Meier analysis demonstrated 2-year PFS to be 100%, which is substantially higher than reported PFS in this clinical population using standard-of-care MRI-guided RT. CONCLUSIONS [68Ga]-DOTATATE PET/MR-guidance can improve PFS following postoperative RT in subtotally resected WHO-2 meningiomas.

Background: While MRI is the gold standard for meningioma diagnosis and treatment planning, it poses limitations in differentiating residual/recurrent disease from post-treatment-change. 68Ga-DOTATATE PET/MR of 50 min with standardized uptake value (SUV) analysis has demonstrated clinical utility in patients with meningioma. However, SUV is considered semi-quantitative with limited reproducibility depending on several variable parameters not accounted for in its definition. Dynamic PET acquisitions enable parametric imaging accounting for post-injection time to improve quantification. Our purpose was to assess feasibility and clinical utility of dynamic 68Ga-DOTATATE PET/MR with multi-parametric SUV and Patlak analysis in the diagnosis and management of intracranial meningioma. Results: 19 subjects with meningioma underwent dynamic 68Ga-DOTATATE PET/MR. Time-activity curves were generated in 84 volumes of interest (53 meningioma, 9 post-treatment-change, 22 cranial blood pool reference in superior sagittal sinus, SSS). Region-specific net binding rate constant Ki was determined using the standard and generalized Patlak (sPatlak and gPatlak) methods with a population-based reference input function. Absolute and relative mean and maximum SUVs were extracted from the 50 minutes (SUV50) and the last 10 minutes (SUV10) of acquisition. Spearman correlation, Mann-Whitney, and Wilcoxon tests were performed. In meningioma, absolute and relative maximum SUV50 demonstrated a strong, significant, positive correlation with sPatlak Ki (r = 0.82, p < 0.0001 and r = 0.85, p < 0.0001, respectively). Similar results were found in post-treatment-change regions (r = 0.88, p = 0.007 and r = 0.83, p = 0.015, respectively). Mean SUV50 demonstrated similar correlations with sPatlak Ki in both subgroups. No significant differences were observed between sPatlak and gPatlak Ki correlations with SUV. All SUV and Ki metrics were significantly higher in meningioma versus post-treatment-change regions. SUV50 and SUV10 metrics for each sub-cohort were not significantly different. No lesions were reclassified based on SUV10 or Ki compared to SUV50. Conclusions: Multi-parametric SUV and Patlak Ki analysis with 68Ga-DOTATATE PET/MR is feasible and can differentiate meningioma from post-treatment-change. Ki may improve quantification of postoperative residual/ recurrent meningioma. SUV10 and SUV50 yielded comparable quantification suggesting feasibility for shorter PET scans.Trial Registration Number (ClinicalTrials.gov ID): NCT04081701, Registration Date: September 9, 2019

Abstract BACKGROUND MRI, the standard of care (SOC) for meningioma radiotherapy planning, lacks sensitivity for postoperative small volume disease and osseous or parenchymal invasion. BN003 (NCT03180268) randomizes patients with WHO-2 meningiomas and MRI-determined GTR to observation or 60 Gy IMRT to the resection bed. More sensitive and specific imaging biomarkers may improve clinical outcomes in meningioma by limiting unnecessary radiation of normal tissues and improving radiation targeting. [68Ga]-DOTATATE is a PET radiotracer targeting somatostatin receptor 2 (SSTR2), a highly sensitive and specific meningioma biomarker. We developed a dedicated DOTATATE brain PET/MRI protocol allowing meningioma differentiation from post-treatment change, using SUV analysis and Patlak modeling. Our prospective observational trial (NCT04081701) has imaged over 90 patients with meningioma. This IRB-approved study evaluated PFS in patients with WHO-2 tumors and postoperative GTR by [68Ga]-DOTATATE PET/MRI who were managed solely with active surveillance. We hypothesized that the PFS of patients with GTR by PET/MRI managed with active surveillance would be higher than for patients with MRI-determined GTR, using NRG-BN003’s observation arm (randomized trial comparing observation to fractionated radiotherapy) as a reference standard. METHODS 92 patients with SSTR2-positive brain neoplasms were enrolled between 9/2019 and 5/2022 and imaged according to our previously published protocol. 8 patients met inclusion criteria (WHO-2 meningioma & postoperative PET/MR GTR) and were followed with SOC MRI. Kaplan-Meier survival analysis was performed. RESULTS 5/8 subjects (62.5%) were women; the mean age was 67 years. MRI follow-up data were available for a mean of 19.75 months (range: 7-38 months). One subject (12.5%) progressed at 21 months; the remainder remain progression-free. Kaplan-Meier analysis demonstrated 3-year PFS to be 80%, which is substantially higher than the reported 3-year PFS of 69% in the literature. CONCLUSIONS [68Ga]-DOTATATE PET can improve the specificity of imaging-based assessment of the extent of resection of WHO-2 meningiomas.

Background and PurposeMeningiomas, the most common primary intracranial tumor, are vascular neoplasms that express somatostatin receptor-2 (SSTR2). The purpose of this investigation was to evaluate if a relationship exists between tumor vascularity and SSTR2 expression, which may play a role in meningioma prognostication and clinical management.Materials and MethodsGallium-68-DOTATATE PET/MRI with dynamic contrast-enhanced (DCE) perfusion was prospectively performed. Clinical and demographic patient characteristics were recorded. Tumor volumes were segmented and superimposed onto parametric DCE maps including flux rate constant (Kep), transfer constant (Ktrans), extravascular volume fraction (Ve), and plasma volume fraction (Vp). Meningioma PET standardized uptake value (SUV) and SUV ratio to superior sagittal sinus (SUVRSSS) were recorded. Pearson correlation analyses were performed. In a random subset, analysis was repeated by a second investigator, and intraclass correlation coefficients (ICCs) were determined.ResultsThirty-six patients with 60 meningiomas (20 WHO-1, 27 WHO-2, and 13 WHO-3) were included. Mean Kep demonstrated a strong significant positive correlation with SUV (r = 0.84, p < 0.0001) and SUVRSSS (r = 0.81, p < 0.0001). When stratifying by WHO grade, this correlation persisted in WHO-2 (r = 0.91, p < 0.0001) and WHO-3 (r = 0.92, p = 0.0029) but not WHO-1 (r = 0.26, p = 0.4, SUVRSSS). ICC was excellent (0.97–0.99).ConclusionDOTATATE PET/MRI demonstrated a strong significant correlation between tumor vascularity and SSTR2 expression in WHO-2 and WHO-3, but not WHO-1 meningiomas, suggesting biological differences in the relationship between tumor vascularity and SSTR2 expression in higher-grade meningiomas, the predictive value of which will be tested in future work.

Multiple approaches with [68Ga]-DOTATATE, a somatostatin analog PET radiotracer, have demonstrated clinical utility in evaluation of meningioma but have not been compared directly. Our purpose was to compare diagnostic performance of different approaches to quantitative brain [68Ga]-DOTATATE PET/MRI analysis in patients with suspected meningioma recurrence and to establish the optimal diagnostic threshold for each method. Patients with suspected meningioma were imaged prospectively with [68Ga]-DOTATATE brain PET/MRI. Lesions were classified as meningiomas and post-treatment change (PTC), using follow-up pathology and MRI as reference standard. Lesions were reclassified using the following methods: absolute maximum SUV threshold (SUV), SUV ratio (SUVR) to superior sagittal sinus (SSS) (SUVRsss), SUVR to the pituitary gland (SUVRpit), and SUVR to the normal brain parenchyma (SUVRnorm). Diagnostic performance of the four methods was compared using contingency tables and McNemar's test. Previously published pre-determined thresholds were assessed where applicable. The optimal thresholds for each method were identified using Youden's J statistics. 166 meningiomas and 41 PTC lesions were identified across 62 patients. SUV, SUVRsss, SUVRpit, and SUVRnorm of meningioma were significantly higher than those of PTC (P < 0.0001). The optimal thresholds for SUV, SUVRsss, SUVRpit, and SUVRnorm were 4.7, 3.2, 0.3, and 62.6, respectively. At the optimal thresholds, SUV had the highest specificity (97.6%) and SUVRsss had the highest sensitivity (86.1%). An ROC analysis of SUV, SUVRsss, SUVRpit, and SUVRnorm revealed AUC of 0.932, 0.910, 0.915, and 0.800, respectively (P < 0.0001). Developing a diagnostic threshold is key to wider clinical translation of [68Ga]-DOTATATE PET/MRI in meningioma evaluation. We found that the SUVRsss method may have the most robust combination of sensitivity and specificity in the diagnosis of meningioma in the post-treatment setting, with the optimal threshold of 3.2. Future studies validating our findings in different patient populations are needed to continue optimizing the diagnostic performance of [68Ga]-DOTATATE PET/MRI in meningioma patients.Trial registration: ClinicalTrials.gov Identifier: NCT04081701. Registered 9 September 2019. https://clinicaltrials.gov/ct2/show/NCT04081701 .

Abstract PURPOSE Postoperative PET/MRI with [68Ga]-DOTATATE can differentiate residual meningioma from postsurgical change, aid in target delineation, and portend a more favorable dosimetry with decreased PTV and organ-at-risk dose. Our purpose was to demonstrate utility of DOTATATE PET/MR for radiosurgical treatment (RT) response assessment in meningiomas. METHODS Patients underwent postoperative radiation treatment planning using DOTATATE PET/MRI as part of our IRB-approved prospective trial. Both DOTATATE PET and gadolinium-enhanced T1 weighted MR imaging were incorporated in RT-planning. All patients underwent follow-up DOTATATE PET/MRI at 6-12 months following completion of radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVR) of lesion/ superior sagittal sinus SUV were obtained. RANO criteria were applied to determine significance of change in size. Statistical analyses were performed using paired t-tests. RESULTS 13 patients (15% WHO-I, 54% WHO-II, 23% WHO-III, 8% WHO grade unknown) were followed postoperatively with pre- and post-RT DOTATATE PET/MRI. 29 meningiomas were treated. 46% (6/13) of subjects received SBRT and 54% (7/13) received SRS. Post-RT DOTATATE PET/MRI demonstrated a 46.4% SUV decrease (p-value = 0.0001) and a 60.8% SUVR decrease (p-value < 0.0001). Of 21 measurable lesions, the size product decreased by 21%; while this decrease was statistically significant (p-value = 0.0008), it was below the 25% decrease defined as clinically significant by RANO guidelines. To date, all patients remain stable radiographically without evidence of recurrence (mean follow-up post RT: 14 months; range: 6-24 months). CONCLUSIONS DOTATATE PET SUV and SUVR demonstrated marked, significant decrease post radiosurgery. Lesion size decrease was statistically significant but not clinically significant by RANO criteria. DOTATATE PET/MR thus represents a promising approach to aid in response assessment for radiosurgically treated meningiomas. Longer-term follow-up is needed to determine the correlation between the degree of post-RT SUV and/or SUVR decrease and progression-free-survival.

Most head and neck paragangliomas (PGLs) are biochemically silent and often present with recurrence and metastases in association with hereditary syndromes. Whole-body functional imaging is increasingly used to detect tumor extent and guide treatment planning of PGLs. [68Ga]-DOTATATE, which targets somatostatin receptor 2 (SSTR2) overexpression, has emerged as a sensitive functional imaging modality in PGLs. We present a patient with metastatic glomus caroticum PGL in whom [68Ga]-DOTATATE PET/MRI provided a more accurate characterization of metastatic extent, as compared to gadolinium-enhanced MRI of the neck and whole body [18F]-FDG PET/CT. We then review the current literature and discuss the imaging implications of [68Ga]-DOTATATE PET/MRI in PGLs.