68Ga-DOTATATE Positron Emission Tomography Research Articles

Learning Without Real Data Annotations to Detect Hepatic Lesions in PET Images.

Deep neural networks have been recently applied to lesion identification in fluorodeoxyglucose (FDG) positron emission tomography (PET) images, but they typically rely on a large amount of well-annotated data for model training. This is extremely difficult to achieve for neuroendocrine tumors (NETs), because of low incidence of NETs and expensive lesion annotation in PET images. The objective of this study is to design a novel, adaptable deep learning method, which uses no real lesion annotations but instead low-cost, list mode-simulated data, for hepatic lesion detection in real-world clinical NET PET images. We first propose a region-guided generative adversarial network (RG-GAN) for lesion-preserved image-to-image translation. Then, we design a specific data augmentation module for our list-mode simulated data and incorporate this module into the RG-GAN to improve model training. Finally, we combine the RG-GAN, the data augmentation module and a lesion detection neural network into a unified framework for joint-task learning to adaptatively identify lesions in real-world PET data. The proposed method outperforms recent state-of-the-art lesion detection methods in real clinical 68Ga-DOTATATE PET images, and produces very competitive performance with the target model that is trained with real lesion annotations. With RG-GAN modeling and specific data augmentation, we can obtain good lesion detection performance without using any real data annotations. This study introduces an adaptable deep learning method for hepatic lesion identification in NETs, which can significantly reduce human effort for data annotation and improve model generalizability for lesion detection with PET imaging.

Location-Aware Encoding for Lesion Detection in 68Ga-DOTATATE Positron Emission Tomography Images.

Lesion detection with positron emission tomography (PET) imaging is critical for tumor staging, treatment planning, and advancing novel therapies to improve patient outcomes, especially for neuroendocrine tumors (NETs). Current lesion detection methods often require manual cropping of regions/volumes of interest (ROIs/VOIs) a priori, or rely on multi-stage, cascaded models, or use multi-modality imaging to detect lesions in PET images. This leads to significant inefficiency, high variability and/or potential accumulative errors in lesion quantification. To tackle this issue, we propose a novel single-stage lesion detection method using only PET images. We design and incorporate a new, plug-and-play codebook learning module into a U-Net-like neural network and promote lesion location-specific feature learning at multiple scales. We explicitly regularize the codebook learning with direct supervision at the network's multi-level hidden layers and enforce the network to learn multi-scale discriminative features with respect to predicting lesion positions. The network automatically combines the predictions from the codebook learning module and other layers via a learnable fusion layer. We evaluate the proposed method on a real-world clinical 68Ga-DOTATATE PET image dataset, and our method produces significantly better lesion detection performance than recent state-of-the-art approaches. We present a novel deep learning method for single-stage lesion detection in PET imaging data, with no ROI/VOI cropping in advance, no multi-stage modeling and no multi-modality data. This study provides a new perspective for effective and efficient lesion identification in PET, potentially accelerating novel therapeutic regimen development for NETs and ultimately improving patient outcomes including survival.

Case report: Efficacy of lutetium-177 oxodotreotide for neuroendocrine tumor with central nervous system metastases

Neuroendocrine tumors (NETs) rarely metastasize to the brain. However, when they occur, NET brain metastases are associated with a poor prognosis. Due to their low incidence, NET brain metastases are poorly studied, with few data to guide a consensus for management. Prior reports have documented treatment with chemotherapy, resection, whole brain radiation therapy, and stereotactic radiosurgery, all with low rates of survival. We present a case of a patient with type 3 well-differentiated gastric NET with widespread metastatic disease, including central nervous system lesions in the pineal gland and left cerebellopontine angle (CPA), which were avid on 68Ga-dotatate positron emission tomography. The patient received four doses of 200 mCi (7.4 GBq) lutetium-177 oxodotreotide (177Lu-dotatate) administered every 8 weeks over the course of 6 months. The treatments provided local control of the pineal and CPA lesions for 23 months until the development of diffuse leptomeningeal progression that necessitated further therapies. 177Lu-dotatate may be a viable treatment for local control of NET brain metastases. More studies are needed to validate its efficacy in this clinical scenario.

Novel Approach for Assessing Postinfarct Myocardial Injury and Inflammation Using Hybrid Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.

Novel Approach for Assessing Postinfarct Myocardial Injury and Inflammation Using Hybrid Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.

Gastroenteropancreatic Neuroendocrine Tumor Metastasis to the Heart: Evaluation of Imaging Manifestations

Neuroendocrine tumors (NET) may affect the heart by cardiac metastasis or carcinoid heart disease. NET metastasis to the heart is rare, with limited data characterizing it. We sought to evaluate 68Ga-DOTATATE PET scan imaging features and associated cardiac imaging characteristics where available in those with NET cardiac metastases. 68Ga-DOTATATE positron emission tomography (PET)/CT scans performed on patients with gastroenteropancreatic (GEP) NET at our institution were reviewed for cardiac involvement. Those identified with cardiac metastases had their electronic medical record, transthoracic echocardiogram (TTE) and cardiac magnetic resonance imaging (MRI) reviewed for characterization. From a total of 1426 68Ga-DOTATATE PET/CT scans performed on patients with GEP-NET, 25 (1.75%) had cardiac uptake consistent with metastasis. Of these, 22 had myocardial metastases (29 distinct myocardial lesions: left ventricle - 16, right ventricle - 6, and ventricular septum -7) and 3 had periradial lymph node involvement only. NET patients with cardiac metastases as identified by DOTATATE scan did not appear to have any hemodynamically significant TTE features, aside from those (2/25) who had concomitant carcinoid heart disease. Of the 14 patients who had available TTE for review, only one with high metastatic cardiac tumor burden had detectable cardiac mass. Of the 6 cases who had available MRI, all had metastatic cardiac lesions seen with excellent correlation with tumor localization on 68Ga-DOTATATE PET scan. 68Ga-DOTATATE PET has excellent capability for the diagnosis of cardiac NET metastasis. Cardiac MRI may provide further anatomic and tissue characterization evaluation. Those with myocardial NET metastases without carcinoid heart disease did not have significant hemodynamic effect based on echocardiographic criteria.

68Ga-DOTATATE PET-Based Radiation Contouring Creates More Precise Radiation Volumes for Patients With Meningioma

Radiation treatment planning for meningiomas traditionally involves magnetic resonance imaging (MRI) contrast enhanced images to define residual tumor. However, the gross tumor volume may be difficult to delineate for patients with a meningioma in the skull base sagittal sinus or after resection. Advanced positron emission tomography (PET) imaging using 68Ga-DOTATATE, which has been shown to be more sensitive and specific than MRI imaging, can be used for target volume delineation in these circumstances. We hypothesized that 68Ga-DOTATATE PET scan-based treatment planning would lead to smaller radiation volumes and would detect additional areas of disease compared with standard MRI alone. Our data evaluated retrospective, deidentified, and blinded gross tumor volume contour delineation with 7 central nervous system (CNS) specialists (4 CNS radiation oncologists and 3 neuroradiologists) for 25 patients with a meningioma diagnosis who received both a 68Ga-DOTATATE PET and an MRI for radiation treatment planning. Both the MRI and the PET were nonsequentially contoured by each physician for each patient. The median MRI volume for each physician ranged from 16.94-25.53 cm3. The median PET volume for each physician ranged from 2.09 to 8.36 cm3. The median PET volume was smaller for each physician. In addition, 7 of the 25 patients (28%) hadnew nonadjacent areas contoured on PET by at least 6 of the 7 physicians that were not contoured by these physicians on the corresponding MRI. These new areas would not have been in the traditional MRI-based volumes. Our study supports that 68Ga-DOTATATE PET imaging may help radiation oncologists create more precise radiation treatment volumes through finding undetected areas of disease not seen on MRI. Treatment planning guided by 68Ga-DOTATATE PET should be studied prospectively.

Glucocorticoid Receptor Antagonism Upregulates Somatostatin Receptor Subtype 2 Expression in ACTH-Producing Neuroendocrine Tumors: New Insight Based on the Selective Glucocorticoid Receptor Modulator Relacorilant.

Somatostatin exhibits an inhibitory effect on pituitary hormone secretion, including inhibition of growth hormone and adrenocorticotropic hormone (ACTH), and it can have antisecretory and antitumor effects on neuroendocrine tumors (NETs) that express somatostatin receptors. Although the precise mechanism remains unclear, the finding that glucocorticoids downregulate somatostatin receptor subtype 2 (SSTR2) expression has been used to explain the lack of efficacy of traditional SSTR2-targeting analogs in patients with ACTH-secreting NETs. Glucocorticoid receptor (GR) antagonism with mifepristone has been shown to reverse the glucocorticoid-induced downregulation of SSTR2; however, the effects of GR modulation on SSTR2 expression in ACTH-secreting NETs, particularly corticotroph pituitary tumors, are not well known. The current study presents new insight from in vitro data using the highly selective GR modulator relacorilant, showing that GR modulation can overcome dexamethasone-induced suppression of SSTR2 in the murine At-T20 cell line. Additional data presented from clinical case observations in patients with ACTH-secreting NETs suggest that upregulation of SSTR2 via GR modulation may re-sensitize tumors to endogenous somatostatin and/or somatostatin analogs. Clinical, laboratory, and imaging findings from 4 patients [2 ACTH-secreting bronchial tumors and 2 ACTH-secreting pituitary tumors (Cushing disease)] who were treated with relacorilant as part of two clinical studies (NCT02804750 and NCT02762981) are described. In the patients with ectopic ACTH secretion, SSTR2-based imaging (Octreoscan and 68Ga-DOTATATE positron emission tomography) performed before and after treatment with relacorilant showed increased radiotracer uptake by the tumor following treatment with relacorilant without change in tumor size at computed tomography. In the patients with Cushing disease who received relacorilant prior to scheduled pituitary surgery, magnetic resonance imaging after a 3-month course of relacorilant showed a reduction in tumor size. Based on these findings, we propose that GR modulation in patients with ACTH-secreting NETs upregulates previously suppressed SSTR2s, resulting in tumor-specific antisecretory and anti-proliferative effects. The effect of relacorilant on pituitary corticotroph tumors is being investigated in an ongoing phase 3 study (NCT03697109; EudraCT 2018-003096-35).

NIMG-66. USING 68GA-DOTATATE PET FOR POSTOPERATIVE GAMMA KNIFE RADIOSURGERY PLANNING IN PATIENTS WITH MENINGIOMA

Abstract BACKGROUND Patients with meningiomas are typically treated with maximal safe surgical resection. After subtotal resection or at the time of tumor recurrence, stereotactic radiosurgery (SRS) is often used as the treatment of choice. While magnetic resonance imaging (MRI) is typically used for SRS target delineation, differentiating tumor growth from postoperative change can be challenging. 68Ga-DOTATATE, a positron emission tomography (PET) radiotracer targeting the somatostatin receptor type 2 (SSTR2), has been shown to be a reliable biomarker of meningiomas. METHODS We present a consecutive case series of 13 patients with pathology-proven meningioma who received a 68Ga-DOTATATE PET prior to SRS between April 2019 and April 2021. Treatment planning was done at first using MRI only. The DOTATATE-PET images were then used to assess the accurate identification of tumor. RESULTS Ten of the patients had WHO grade 2 meningioma and three patients had WHO grade 1 tumor. Nine patients had recurrent meningiomas and four patients had newly diagnosed disease. Overall, the 68Ga-DOTATATE PET scan revealed additional tumor beyond what was seen on MRI in 5/13 patients. The SRS plan was changed to intensity-modulated radiation therapy (IMRT) for three patients and to octreotide injection in one patient. In one patient, after 68Ga-DOTATATE PET identified previously unrecognized recurrent meningioma in the resection cavity, SRS was performed. In three others, questionable tumor recurrence was seen on MRI, and then confirmed on 68Ga-DOTATATE-PET, but patient observation only was continued due to the small lesion size. CONCLUSION Incorporation of 68Ga-DOTATATE PET data changed SRS treatment in 5/13 our patients with meningioma after prior surgery. We have made this a routine part of our treatment planning and we recommend this method to optimize the use of SRS or RT in these patients. Further data collection is ongoing.

Synergism of Checkpoint Inhibitors and Peptide Receptor Radionuclide Therapy in the Treatment of Pituitary Carcinoma.

ContextAggressive pituitary tumors that have progressed following temozolomide have limited treatment options. Peptide receptor radionuclide therapy and immunotherapy may have a complementary role in the management of these tumors.MethodsWe provide follow-up data on a previously reported patient with a hypermutated recurrent tumor. The patient in this report provided written informed consent for tumor sequencing and review of medical records on an institutional review board–approved research protocol (NCT01775072).ResultsThis patient with a corticotroph pituitary carcinoma with alkylator-induced somatic hypermutation has remained on treatment with ipilimumab and nivolumab for 3.5 years and remains clinically well. After an initial partial response to checkpoint inhibitors, she has had several recurrences that have undergone immunoediting of subclonal mutations, which have been effectively treated with continuation of immunotherapy, surgery, external beam radiation, and 177Lu-DOTATATE. Following external beam radiotherapy (RT), she had radiographic evidence of an abscopal response at a distant site of disease suggesting a synergism between checkpoint inhibitors and RT. Following treatment with 177Lu-DOTATATE, the patient had a partial response with a 61% reduction in volume of the target lesion.ConclusionIn patients with aggressive pituitary tumors, treatment with checkpoint inhibitors may trigger an abscopal response from RT. With appropriate selection, an additional efficacious treatment, 177Lu-DOTATATE, may be available for a limited number of patients with aggressive pituitary tumors, including patients who have progressed on temozolomide and exhibit increased somatostatin receptor expression on 68Ga-DOTATATE positron emission tomography.

Pericoronary and periaortic adipose tissue density are associated with inflammatory disease activity in Takayasu arteritis and atherosclerosis.

AimsTo examine pericoronary adipose tissue (PCAT) and periaortic adipose tissue (PAAT) density on coronary computed tomography angiography for assessing arterial inflammation in Takayasu arteritis (TAK) and atherosclerosis.Methods and resultsPCAT and PAAT density was measured in coronary (n = 1016) and aortic (n = 108) segments from 108 subjects [TAK + coronary artery disease (CAD), n = 36; TAK, n = 18; atherosclerotic CAD, n = 32; matched controls, n = 22]. Median PCAT and PAAT densities varied between groups (mPCAT: P < 0.0001; PAAT: P = 0.0002). PCAT density was 7.01 ± standard error of the mean (SEM) 1.78 Hounsfield Unit (HU) higher in coronary segments from TAK + CAD patients than stable CAD patients (P = 0.0002), and 8.20 ± SEM 2.04 HU higher in TAK patients without CAD than controls (P = 0.0001). mPCAT density was correlated with Indian Takayasu Clinical Activity Score (r = 0.43, P = 0.001) and C-reactive protein (r = 0.41, P < 0.0001) and was higher in active vs. inactive TAK (P = 0.002). mPCAT density above −74 HU had 100% sensitivity and 95% specificity for differentiating active TAK from controls [area under the curve = 0.99 (95% confidence interval 0.97–1)]. The association of PCAT density and coronary arterial inflammation measured by 68Ga-DOTATATE positron emission tomography (PET) equated to an increase of 2.44 ± SEM 0.77 HU in PCAT density for each unit increase in 68Ga-DOTATATE maximum tissue-to-blood ratio (P = 0.002). These findings remained in multivariable sensitivity analyses adjusted for potential confounders.ConclusionsPCAT and PAAT density are higher in TAK than atherosclerotic CAD or controls and are associated with clinical, biochemical, and PET markers of inflammation. Owing to excellent diagnostic accuracy, PCAT density could be useful as a clinical adjunct for assessing disease activity in TAK.

Radiomics-Based Texture Analysis of 68Ga-DOTATATE Positron Emission Tomography and Computed Tomography Images as a Prognostic Biomarker in Adults With Neuroendocrine Cancers Treated With 177Lu-DOTATATE

PurposeNeuroendocrine tumors (NET) are rare cancers with variable behavior. A better understanding of prognosis would aid individualized management. The aim of this hypothesis-generating pilot study was to investigate the prognostic potential of tumor heterogeneity and tracer avidity in NET using texture analysis (TA) of 68Ga-DOTATATE positron emission tomography (PET) and non-enhanced computed tomography (CT) performed at baseline in patients treated with 177Lu-DOTATATE. It aims to justify a larger-scale study to evaluate its clinical value.MethodsThe pretherapy 68Ga-DOTATATE PET-CT scans of 44 patients with metastatic NET (carcinoid, pancreatic, thyroid, head and neck, catecholamine-secreting, and unknown primary NET) treated with 177Lu-DOTATATE were analyzed retrospectively using commercially available texture analysis research software. Image filtration extracted and enhanced objects of different sizes (fine, medium, coarse), then quantified heterogeneity by statistical and histogram-based parameters (mean intensity, standard deviation, entropy, mean of positive pixels, skewness, and kurtosis). Regions of interest were manually drawn around up to five of the most 68Ga-DOTATATE avid lesions for each patient. 68Gallium uptake on PET was quantified as SUVmax and SUVmean. Associations between imaging and clinical markers with progression-free (PFS) and overall survival (OS) were assessed using univariate Kaplan-Meier analysis. Independence of the significant univariate markers of survival was tested using multivariate Cox regression analysis.ResultsMeasures of heterogeneity (higher kurtosis, higher entropy, and lower skewness) on coarse-texture scale CT and unfiltered PET images predicted shorter PFS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness: p=0.03) and shorter OS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness p=0.02). Conventional PET parameters such as SUVmax and SUVmean showed trends towards predicting outcome but were not statistically significant. Multivariate analysis identified that CT-TA (coarse kurtosis: HR=2.57, 95% CI=1.22–5.38, p=0.013) independently predicted PFS, and PET-TA (unfiltered skewness: HR=9.05, 95% CI=1.19–68.91, p=0.033) independently predicted OS.ConclusionThese preliminary data generate a hypothesis that radiomic analysis of neuroendocrine cancer on 68Ga-DOTATATE PET-CT may be of prognostic value and a valuable addition to the assessment of patients.

Can a penalized-likelihood estimation algorithm be used to reduce the injected dose or the acquisition time in 68Ga-DOTATATE PET/CT studies?

BackgroundImage quality and quantitative accuracy of positron emission tomography (PET) depend on several factors such as uptake time, scanner characteristics and image reconstruction methods. Ordered subset expectation maximization (OSEM) is considered the gold standard for image reconstruction. Penalized-likelihood estimation (PL) algorithms have been recently developed for PET reconstruction to improve quantitation accuracy while maintaining or even improving image quality. In PL algorithms, a regularization parameter β controls the penalization of relative differences between neighboring pixels and determines image characteristics. In the present study, we aim to compare the performance of Q.Clear (PL algorithm, GE Healthcare) and OSEM (3 iterations, 8 subsets, 6-mm post-processing filter) for 68Ga-DOTATATE (68Ga-DOTA) PET studies, both visually and quantitatively.Thirty consecutive whole-body 68Ga-DOTA studies were included. The data were acquired in list mode and were reconstructed using 3D OSEM and Q.Clear with various values of β and various acquisition times per bed position (bp), thus generating images with reduced injected dose (1.5 min/bp: β = 300–1100; 1.0 min/bp: β = 600–1400 and 0.5 min/bp: β = 800–2200). An additional analysis adding β values up to 1500, 1700 and 3000 for 1.5, 1.0 and 0.5 min/bp, respectively, was performed for a random sample of 8 studies. Evaluation was performed using a phantom and clinical data. Two experienced nuclear medicine physicians blinded to the variables assessed the image quality visually.ResultsClinical images reconstructed with Q.Clear, set at 1.5, 1.0 and 0.5 min/bp using β = 1100, 1300 and 3000, respectively, resulted in images with noise equivalence to 3D OSEM (1.5 min/bp) with a mean increase in SUVmax of 14%, 13% and 4%, an increase in SNR of 30%, 24% and 10%, and an increase in SBR of 13%, 13% and 2%. Visual assessment yielded similar results for β values of 1100–1400 and 1300–1600 for 1.5 and 1.0 min/bp, respectively, although for 0.5 min/bp there was no significant improvement compared to OSEM.Conclusion68Ga-DOTA reconstructions with Q.Clear, 1.5 and 1.0 min/bp, resulted in increased tumor SUVmax and in improved SNR and SBR at a similar level of noise compared to 3D OSEM. Q.Clear with β = 1300–1600 enables one-third reduction of acquisition time or injected dose, with similar image quality compared to 3D OSEM.

Pericoronary adipose tissue density is associated with clinical disease activity in Takayasu arteritis and coronary arterial inflammation measured by 68Ga-DOTATATE PET in atherosclerosis

Abstract Background Coronary artery disease (CAD) is an under-recognized complication of intense arterial inflammation in Takayasu arteritis (TAK). While pericoronary adipose tissue (PCAT) density is associated with arterial inflammation in CAD patients, this relationship has not previously been studied in TAK patients, nor directly compared with coronary arterial inflammation measured by 68Ga-DOTATATE positron emission tomography (PET). Purpose To compare PCAT density with clinical, biochemical and molecular imaging markers of inflammation in TAK and CAD patients. Methods PCAT density was quantified from computed tomography coronary angiography (CTCA) around each of the 17 coronary segments in patients with: (1) TAK and CAD, (2) atherosclerotic CAD, and (3) age and gender-matched healthy controls, using semi-automated software (Autoplaque). In TAK patients, PCAT density was compared to the Indian Takayasu Clinical Activity Score (ITAS) and high-sensitivity C-reactive protein (CRP). In CAD patients, PCAT density was compared to local arterial inflammation measured by coronary motion-frozen 68Ga-DOTATATE PET using image registration software (FusionQuant), and systemic (aortic) inflammation using 18F-fluorodeoxyglucose (FDG) PET. Data was acquired either during routine clinical care or prior research that established 68Ga-DOTATATE as an experimental marker of arterial inflammation that binds macrophage somatostatin receptor-2 in atherosclerotic plaques (NCT02021188). Results 60 patients were included (TAK, n=20; CAD, n=20; healthy, n=20). Non-calcified plaque burden (TAK: 95.2%; CAD: 90.4%, p&amp;lt;0.0001) and CRP (TAK: 25.2 ±SD 16.1 mg/L; CAD: 2.5 ±SD 1.7 mg/L, p=0.04) were greater in TAK than CAD patients. PCAT density varied significantly among the three groups (median [IQR] TAK: −72.9 [−81.2 to -66.1] Hounsfield unit [HU]; CAD: −79.9 [−88.0 to −72.2]; healthy: −83.8 [−90.1 to −75.8] HU, p&amp;lt;0.0001). Figure: box-plot showing the distribution of PCAT values by group, with corresponding representative multiplanar reconstructed and cross-sectional CTCA images with surrounding PCAT density displayed by color table in left anterior descending arteries. PCAT density was significantly associated with ITAS (r=0.61, p=0.004) and CRP (r=0.43, p=0.03) in TAK patients, and coronary 68Ga-DOTATATE maximum tissue-to-blood ratio (r=0.31, p&amp;lt;0.001) in CAD patients. PCAT density was not associated with aortic 18F-FDG uptake in CAD patients, nor subcutaneous (pre-sternal) adipose tissue density in either disease group. No significant patient-level confounders were identified using linear mixed-effects regression modelling. Conclusion PCAT density measured by CTCA is greater in TAK than CAD patients, and is associated with clinical and biochemical markers of disease activity in TAK, and coronary arterial inflammation measured by 68Ga-DOTATATE PET in CAD. PCAT could be a useful, easy to measure marker of coronary inflammation and disease activity in both TAK and CAD. PCAT density is greater in TAK than CAD Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Wellcome Trust

Actualización sobre el manejo diagnóstico y terapéutico del feocromocitoma y el paraganglioma

Pheochromocytomas and paragangliomas are catecholamine-producing tumours originating from chromaffin cells of the sympathetic nervous system of the adrenal medulla or extra-adrenal chromaffin tissue, respectively. They can be sporadic or be associated with genetic diseases in up to 30% of cases. Biochemical confirmation of the elevation of plasma and/or urinary metanephrines will establish the diagnosis of pheochromocytoma, whereas computed tomography or magnetic resonance imaging is used for the initial location diagnosis. In metastatic pheochromocytoma, 123I-metaiodobenzylguanidine (MIBG) scintigraphy and 18F-FDG or 68Ga-DOTATATE positron emission tomography may be helpful. Surgical resection, the only curative option in these patients, is the treatment of choice for pheochromocytomas and paragangliomas being correct preoperative preparation essential to reduce morbidity and mortality. Malignant pheochromocytoma is a rare entity that can only be diagnosed when metastases are present. There is no effective curative treatment; genetic predisposition, tumor development, disease progression and location of metastases will determine its prognosis.

The GALANT trial: study protocol of a randomised placebo-controlled trial in patients with a 68Ga-DOTATATE PET-positive, clinically non-functioning pituitary macroadenoma on the effect of lanreotide on tumour size

IntroductionAt present, there is no approved medical treatment option for patients with non-functioning pituitary adenoma. A number of open-label studies suggest that treatment with somatostatin analogues may prevent tumour progression....

Topical Sensor for the Assessment of Injection Quality for 18F-FDG, 68Ga-PSMA and 68Ga-DOTATATE Positron Emission Tomography

IntroductionCalculation of the standard uptake value (SUV) and image quality in positron emission tomography (PET) hinges on accurate dose delivery. Extravasation or partial extravasation of the radiopharmaceutical dose can undermine SUV and image quality, and contribute to unnecessary imaging (time and CT dose). Topical sensor characterisation of injections has been reported, with extravasation rates ranging from 9% to 23% for 18F-FDG after manual injection. MethodA single site, single PET/CT scanner was used to characterise injections using an autoinjector with standardised apparatus, flush volume and infusion rate using 18F-FDG, 68Ga-PSMA and 68Ga-DOTATATE; more reflective of Australian PET facilities. 296 patients with topical application of LARA sensors were retrospectively analysed. ResultsOnly 1.1% of studies showed evidence of partial dose extravasation. In total, 9.1% were identified to have an injection anomaly (including venous retention). No statistically significant differences were noted across the radiopharmaceuticals for demographic data. Although not demonstrating a statistically significant correlation, there was more extravasated doses associated with female patients (P = .334), right side (P = .372), and hand injections (P = .539). Extravasation was independent of dose administered (P = .495), the radiopharmaceutical (P = .887), who injected the dose (P = .343), height (P = .438), weight (P = .607) or age (P = .716). Extravasation was associated with higher glucose levels (P < .001), higher t-half (P = .019) and higher aUCR10, tc50, aUCR1 and c1 (all P < .001). ConclusionTopical monitoring and characterisation of PET dose administration is possible and practical with the LARA device. Extravasation and partial extravasation of PET doses are not only readily detected but they are also preventable. The LARA device can provide the insights into variables that could eliminate extravasation as a cause of image quality or SUV accuracy issues.

68Ga-DOTATATE PET/CT Compared with 131I-MIBG SPECT/CT in the Evaluation of Neural Crest Tumors.

Objective(s): 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) has shown promising results in imaging of neural crest tumors (NCT). Herein, we compared the performance of 68Ga-DOTATATE PET/CT and 131I-MIBG single photon emission computed tomography (SPECT)/CT in the initial diagnosis, staging and follow-up of patients with NCTs.Methods:Twenty-five patients (males:females=8:17; age range=2–71 years) with clinically proven or suspicious neuroblastoma, pheochromocytoma (PCC) or paraganglioma (PGL) were enrolled in this prospective study and underwent both 68Ga-DOTATATE PET/CT and 131I-MIBG SPECT/CT. A composite reference standard derived from histopathological information, together with anatomical and functional imaging findings, was used to validate the results. Imaging findings were assessed on a per-patient and on a per-lesion basis. Sensitivity and accuracy were assessed using McNemar’s test.Results:Referring to radiological imaging and histopathological findings as reference standard, 68Ga-DOTATATE and 131I-MIBG scans showed a sensitivity and accuracy of (100%, 96%) and (86.7%, 88%), respectively, on a per-patient basis. In PCC/PGL patients, on a per-patient basis, the sensitivity of 68Ga-DOTATATE was 100% and that of 131I-MIBG was 77.8%. In neuroblastoma patients, on a per-patient basis, the sensitivities of both 68Ga-DOTATATE and 131I-MIBG were 100%. Overall, in this patient cohort, 68Ga-DOTATATE PET/CT identified 52 lesions and 131I-MIBG SPECT/CT identified only 30 lesions. On a per-lesion analysis, 68Ga-DOTATATE was found to be superior to 131I-MIBG in detecting lesions in all anatomical locations, particularly osseous lesions. According to the McNemar test results, differences were not statistically significant.Conclusion:This relatively small patient cohort suggests 68Ga-DOTATATE PET/CT be superior to 131I-MIBG SPECT/CT in providing particularly valuable information for both primary staging and follow-up in patients with NCT.

A Practical Guide for the Production and PET/CT Imaging of 68Ga-DOTATATE for Neuroendocrine Tumors in Daily Clinical Practice.

Neuroendocrine tumors are a rare form of cancer that arise from neuroendocrine cells and can be present at almost any location throughout the body. Although heterogeneous in presentation, a common denominator among these tumors is the overexpression of somatostatin receptors. 68Ga-DOTATATE is a somatostatin analog labeled with the positron emitter gallium-68 (68Ga). For well-differentiated neuroendocrine tumors, 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) imaging is used for diagnosis, determination of disease burden, and therapy selection. This protocol details the radiolabeling of 68Ga-DOTATATE, quality control, patient preparation, and subsequent PET/CT imaging. Radiolabeling of 68Ga-DOTATATE is performed with a fully automated labeling module coupled to a germanium-68 (68Ge)/68Ga generator. Quality control of the final product evaluates radiochemical purity with instant thin-layer chromatography and solid-phase chromatography, and pH prior to patient injection. Periodic quality control is performed to determine 68Ge breakthrough, sterility, and (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) content. Patient preparation includes patient instructions, a protocol for 68Ga-DOTATATE during treatment with somatostatin analogs, and intravenous administration of the radiopharmaceutical. For PET/CT imaging, the acquisition and reconstruction settings are described. For each step, radiation safety will be highlighted, as well as time constrictions due to the short half-life of 68Ga. Fully automated in-house production and quality control of 68Ga-DOTATATE leads to very high success rates (95%) and produces two to four patient dosages per batch, depending on the yield of the generator. In conclusion, 68Ga-DOTATATE PET/CT imaging is a noninvasive and fast method of providing information on the tumor burden of neuroendocrine tumors (NETs) while also assisting in diagnosis and therapy selection.

SAT-LB059 NET or NOT: Physiological Uptake in Pancreatic Head on Somatostatin Receptor Based Imaging

Introduction Neuroendocrine tumors (NETs) are neoplasms that can arise from the neuroendocrine cells distributed widely throughout the body. Majority of NETs overexpress somatostatin receptors (SSTR) on their cell surface. This biologic characteristic is exploited in the SSTR-based imaging such as 111In octreotide scintigraphy and 68Ga DOTATATE positron emission tomography (PET)/CT. These modalities are currently considered standard for initial evaluation of suspected NETs. Although highly sensitive and specific, recent reports demonstrate a concerning incidence of “false-positive” physiologic uptake of these tracers in the pancreatic head - a confounding common site of NET involvement. Case report: A 78 year-old woman presented to clinic with a year-long history of diarrhea. Serum vasoactive intestinal peptide (VIP) levels were slightly elevated at 134.2 pg/mL. CT showed a mildly enhancing 2.5x1.8x2.8 cm area in the pancreatic uncinate process which corresponded to moderate focal uptake with 68Ga DOTATATE PET/CT. A presumptive diagnosis of NET was made, and the patient was scheduled to undergo Whipple’s surgery. She sought a second opinion at our institution. A subsequent MRI showed no lesion in the uncinate process and the patient’s surgery was deferred. Thereafter, her VIP levels spontaneously normalized. Endoscopic ultrasound (EUS) with fine needle aspiration cytology of the uncinate process showed normal pancreatic acini with no evidence of NET. Conclusion Conspicuous physiological uptake has been reported in the pancreatic head on 16-70% of 68Ga DOTATATE or 68Ga DOTANOC PET/CT scans, and 26% of the 111In octreotide scintigraphy scans.1 Image-based quantitative attempts to distinguish physiologic from pathologic uptake using SUVmax have rendered mixed results. When evaluating SSTR-based imaging uptake in the pancreatic head, patients can benefit from a higher index of suspicion of false positive uptake. Such cases require additional confirmation by means such as MRI or EUS. The patient described above also had mild contrast enhancement on CT, but an MRI didn’t show any corresponding lesion. Because of potential morbidity and mortality related to false positive uptake, a systematic review with evidence-based recommendations for imaging may benefit patient care. 1. Brabander T, et al. Physiological Uptake in the Pancreatic Head on Somatostatin Receptor Scintigraphy Using [111In-DTPA]Octreotide: Incidence and Mechanism. Clin Nucl Med 2017;42:15-9. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

The utility of 68Gallium-DOTATATE PET/CT in the detection of von Hippel-Lindau disease associated tumors

PurposePatients with von Hippel-Lindau (VHL) disease may develop various tumors, including neuroendocrine tumors of the pancreas (PNETs) and adrenal, central nervous system and retinal hemangioblastomas, kidney tumors and more. 68Ga-DOTATATE positron emission tomography (PET)/computerized tomography (CT) has been shown to be highly accurate for tumors with cells expressing somatostatin receptors. We aimed to assess the performance of 68Ga-DOTATATE PET/CT in patients with VHL disease. MethodsPatients with a diagnosis of VHL were enrolled in a prospective study and underwent surveillance imaging for pancreatic lesions (n = 301). The current analysis includes 73 evaluations with multiple imaging modalities of 36 patients (2.1 ± 0.8 evaluations/patient, range 1–4) for a head-to-head comparison of 68Ga-DOTATATE PET/CT, CT and/or MRI. In this post-hoc analysis we compared the detection rates of various imaging modalities for PNETs and for any extrapancreatic tumors located within the scan field of CT/MRI of the abdomen. Results68Ga-DOTATATE PET/CT detected a total of 206 lesions, CT detected 208 lesions and MRI detected 94 lesions in 61, 66 and 33 scans, respectively. 68Ga-DOTATATE PET/CT (3.4 ± 0.1 per scan) was superior than CT (3.2 ± 0.1 per scan, p = 0.02) with a similar trend when comparing with MRI (2.8 ± 0.1 per scan, p = 0.03) in detecting lesions in any anatomic locations. Conclusions68Ga-DOTATATE PET/CT had a significantly higher detection rate when compared with anatomic imaging for all lesions, and comparable detection rate for pancreatic lesions in VHL patients. Hence, given the higher accuracy and lower radiation exposure associated with 68Ga-DOTATATE PET/CT, its potential role in the surveillance of VHL-associated lesions should be further studied.