BACKGROUND AND PURPOSE Meningiomas are the most common primary intracranial tumors, typically treated with surgery and adjuvant radiation in cases of subtotal resection and/or higher histopathologic grade. Contrast‐enhanced magnetic resonance imaging (MRI) is the gold standard for postoperative assessment and adjuvant treatment planning. However, MRI can have limited accuracy particularly in the presence of posttreatment change. [68Ga]‐DOTATATE is a Positron Emission Tomography (PET) radiotracer targeting somatostatin receptor 2A (SSTR2A). SSTR2A is a reliable biomarker of meningiomas. We report a consecutive case series of 20 patients evaluated with [68Ga]‐DOTATATE PET/MRI, propose a novel approach to quantitative analysis, and discuss clinical implications. METHODS We present a consecutive case series of 20 patients with clinically suspected or pathology‐proven meningioma evaluated between July 2018 and February 2019. [68Ga]‐DOTATATE PET/MRI was obtained in order to confirm the diagnosis or determine tumor recurrence/progression to help guide surgical and/or radiation therapy management in cases in which MRI findings were indeterminate or equivocal. RESULTS Seventeen (85%) patients had undergone prior surgery and 11 (55%) underwent adjuvant radiation therapy. In 17 patients [68Ga]‐DOTATATE confirmed the presence of recurrent meningioma. A total of 49 meningiomas were identified (median: 2 meningiomas/patient, range 0‐14). There was excellent differentiation between meningioma and posttreatment change based on our approach of target lesion/superior sagittal sinus maximum standardized uptake values ratio (16.6 vs. 1.6, P < .0001). CONCLUSIONS [68Ga]‐DOTATATE PET/MRI is a promising tool in the assessment of both treatment naïve and resected/irradiated meningiomas, allowing improved diagnosis and extent of disease evaluation. Future prospective studies are needed to determine utility of [68Ga]‐DOTATATE PET/MRI in treatment response assessment.
OBJECTIVES The aim of this study was to noninvasively detect the anti-inflammatory properties of the novel liver X receptor agonist R211945. BACKGROUND R211945 induces reversal cholesterol transport and modulates inflammation in atherosclerotic plaques. We aimed to characterize with 18F-fluorodeoxyglucose (FDG)–positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced cardiac magnetic resonance (DCE-CMR) inflammation and neovascularization, respectively, in atherosclerotic plaques with R211945 treatment compared with atorvastatin treatment and a control. METHODS Twenty-one atherosclerotic New Zealand white rabbits were divided into 3 groups (control, R211945 [3 mg/kg orally], and atorvastatin [3 mg/kg orally] groups). All groups underwent 18F-FDG–PET/CT and DCE-CMR at baseline and at 1 and 3 months after treatment initiation. Concomitantly, serum metabolic parameters and histology were assessed. For statistical analysis, continuous DCE-CMR and PET/CT outcomes were modeled as linear functions of time by using a linear mixed model, whereas the histological data, animal characteristics data, and nonlinear regression imaging data were analyzed with a 2-tailed Student t test. RESULTS 18F-FDG–PET/CT detected a decrease in mean and maximum standard uptake values (SUV) over time in the R211945 group (both p = 0.001), indicating inflammation regression. The atorvastatin group displayed no significant change (p = 0.371 and p = 0.600, respectively), indicating no progression or regression. The control group demonstrated an increase in SUV (p = 0.01 and p = 0.04, respectively), indicating progression. There was a significant interaction between time and group for mean and maximum SUV (p = 0.0003 and p = 0.0016, respectively). DCE-CMR detected a trend toward difference (p = 0.06) in the area under the curve in the atorvastatin group, suggesting a decrease in neovascularization. There was no significant interaction between time and group (p = 0.6350 and p = 0.8011, respectively). Macrophage and apolipoprotein B immunoreactivity decreased in the R211945 and atorvastatin groups (p < 0.0001 and p = 0.0004, respectively), and R211945 decreased oxidized phospholipid immunoreactivity (p = 0.02). CONCLUSIONS Noninvasive imaging with 18F-FDG–PET/CT and DCE-CMR and histological analysis demonstrated significant anti-inflammatory effects of the LXR agonist R211945 compared with atorvastatin. The results suggest a possible role for LXR agonists in the treatment of atherosclerosis.
Background Meningiomas express high levels of somatostatin receptor 2 (SSTR2). SSTR-2 targeted PET imaging with [68Ga]-DOTATATE can aid with distinguishing residual meningioma from reactive changes in the postoperative setting. We present initial dosimetric analyses, acute events and local control data utilizing [68Ga]-DOTATATE PET/MRI-assisted target delineation for prospectively-treated intermediate-risk meningiomas. Methods Twenty-nine patients underwent DOTATATE PET/MRI meningioma evaluation in 2019. Eight patients with 9 postoperative meningiomas met RTOG 0539 intermediate-risk criteria (recurrent WHO grade I, 1/9; WHO grade II, 8/9). Target volumes were created using DOTATATE PET/MRI to determine residual disease and received a nominal dose of 35.0 Gy over 5 fractions. For comparison, cases were recontoured and planned with MRI alone per RTOG 0539 guidelines. Mean and maximum equivalent 2 Gy doses were generated for target volumes and organs at risk (OAR) within 1 cm of the PTV and compared using Wilcoxon matched pairs signed rank test. Results DOTATATE PET/MRI-guided planning significantly reduced mean PTV (11.12 cm 3 compared to 71.39 cm 3 based on MRI alone, p <0.05) and mean and max dose to the whole brain, optic nerves and scalp. PET/MRI plans resulted in at least 50% reduction of mean and max doses to the lens, eyes, chiasm, cochlea, brainstem, and hippocampi. One patient experienced focal alopecia. There were no local recurrences at 6 months. Conclusion Incorporating DOTATATE-PET/MRI for postoperative target delineation in patients with intermediate-risk intracranial meningiomas results in PTV reduction and decreased OAR dose. Our findings warrant larger studies evaluating DOTATATE-PET/MRI in the radiotherapeutic planning of postoperative meningiomas.
Objectives We sought to determine the anti-atherosclerotic properties of pioglitazone using multi-modality non-invasive imaging techniques. Background Inflammation is an essential component of vulnerable or high risk atheromas. Pioglitazone, a peroxisome proliferator–activated receptor-gamma (PPAR-γ)agonist possesses potent anti-inflammatory properties. We aimed to non-invasively to quantify the anti-inflammatory effects of pioglitazone on atheroma using 18F-fluorodeoxyglucose (18F-FDG)-PET/CT and dynamic contrast enhanced MRI (DCE-MRI). Methods Atherosclerotic plaques were induced in the aorta of fifteen New Zealand White (NZW) rabbits by a combination of hyperlipidemic diet and two balloon endothelial denudations. Nine rabbits continued the same diet whereas six received pioglitazone (10mg/kg orally) in addition to the diet. Twelve animals underwent 18F-FDG-PET/CT and fifteen animals underwent DCE-MRI at baseline, one and three months after treatment initiation. Concomitantly, serum metabolic parameters were monitored. After imaging was completed aortic histological analysis and correlation analysis was performed. Results 18F-FDG-PET/CT detected an increase in average standardized uptake value (SUV) in the control group (p<0.01), indicating progressive inflammation, while stable SUV values were observed in the treatment group, indicating no progression. DCE-MRI detected a significant decrease in area under the curve (AUC) for the pioglitazone group (p<0.01). Immunohistology of the aortas demonstrated a significant decrease in macrophage and oxidized phospholipid immunoreactivity in the pioglitazone group (p=0.04 and p=0.01, respectively) with respect to control animals, underlining the imaging results. Serum metabolic parameters showed no difference between groups. A strong positive correlation between SUV and macrophage density and AUC and neovessels was detected ( r2=0.86, p<0.0001 and r2=0.66, p=0.004, respectively). Conclusions 18F-FDG-PET/CT and DCE-MRI demonstrate non-invasively the anti-inflammatory effects of pioglitazone on atheroma. Both imaging modalities appear suited to monitor inflammation in atherosclerosis.
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