DOTATATE Positron Emission Tomography Research Articles

Bone metastasis manifested 52 years after resection of an apparently benign paraganglioma: A case report

Paraganglioma is derived from the paraganglia tissue in the neck, along the sympathetic trunk, and in the pelvis. Paraganglioma has malignant potential and can metastasize to remote organs such as the liver, lungs, and bones. Most metachronous metastases occur within several years after the initial diagnosis of paraganglioma. Here, we report the case of a 71-year-old male patient who developed bony metastasis 52 years after the resection of a large paraganglioma at the aortic bifurcation. The biopsy-proven paraganglioma metastasis to the lesser trochanter of left femur presented as an avulsion fracture. His normetanephrine level was elevated. DOTATATE PET (positron emission tomography) did not find any other metastatic lesions. The bony metastasis was treated with radiation therapy. We believe that the patient had one of the longest gaps ever reported, 52 years, between the initial diagnosis and metastasis of paraganglioma. This case highlights the importance of long-term surveillance of patients with paraganglioma for metastasis.

Comparison of Whole-Body Ga-68 DOTA TATE Positron Emission Tomography and Magnetic Resonance Imaging in the Detection of Bone Metastasis of Neuroendocrine Tumor in Simultaneous 3T Positron Emission Tomography/Computed Tomography

Comparison of Whole-Body Ga-68 DOTA TATE Positron Emission Tomography and Magnetic Resonance Imaging in the Detection of Bone Metastasis of Neuroendocrine Tumor in Simultaneous 3T Positron Emission Tomography/Computed Tomography

A multidisciplinary approach to the work up and management of pulmonary carcinoid tumors and DIPNECH: a narrative review.

Low and intermediate grade neuroendocrine tumors of the lung are uncommon malignancies representing 2% of all lung cancers. These are termed typical and atypical pulmonary carcinoid tumors. These can arise in the setting of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). The presentation, workup, management and outcomes of patients with these tumors can overlap with more common lung cancers but differ in that many of these patients have a prolonged clinical course. The objective of this narrative review is to summarize the literature and provide evidence and expert-based algorithms for work up and treatment of pulmonary carcinoids and DIPNECH. A search of PubMed and Web of Science databases ending April 15, 2022, with the following keywords "lung carcinoid", "DIPNECH", "lung neuroendocrine," and "bronchopulmonary carcinoid". Pulmonary carcinoid tumors benefit from a multidisciplinary approach. Pre-treatment imaging with contrast-enhanced computed tomography, and DOTATATE positron emission tomography is required. Surgical resection is the gold standard for curative intent, and possibly including sublobar resections. Patients can recur or develop new primaries thus emphasizing the importance of surveillance; national guidelines recommend at least a 10-year follow up. A growing body of literature support the use of endobronchial therapy, with long responses documented. Systemic therapy consists of everolimus, somatostatin analogs, peptide receptor radionuclide therapy, and chemotherapy. Diffuse idiopathic pulmonary neuroendocrine tumor cell hyperplasia is rare, but series suggest somatostatin analogs may confer clinical benefit. Pulmonary carcinoid tumors and DIPNECH are rare. Despite lack of regulatory approvals for advanced disease, multiple options are available but should be sequenced according to the clinical status and disease biology. Each patient should be discussed in a multidisciplinary setting and clinical trials should be considered if available.

Fibroblast Growth Factor-23 Secreting Tumour Induced Osteomalacia

Tumour Induced Osteomalacia (TIO) caused by a Fibroblast-Growth- Factor-23 (FGF-23) secreting tumour is a rare paraneoplastic disorder. Patients often present with non-specific complaints of pain and stiffness however findings of hypophosphataemia and inappropriately suppressed 1,25 dihidroxyvitamin D are almost pathognemonic of this condition. We present a previously healthy 51-year-old man who presented with an 18 month history of body aches, hypophosphataemia, and an incidental finding of atraumatic foot fractures on x-ray. Technetium bone scan identified diffuse skeletal pathologic fractures. He was further found to have persistent hypophosphataemia, suppressed 1-25-dihidroxyvitamin-D, renal phosphate wasting with reduced Tubular Reabsorption of Phosphate (TRP), and an FGF-23 level more than twice the upper limit of normal. Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET), Gallium-68 Dotatate PET and magnetic resonance imaging further identified and characterised a 40 mm FDG and Dotatate-avid lesion in the right third rib. Histopathological examination of a biopsy specimen revealed phosphaturic mesenchymal tumour with positive FGF-23 immunohistochemical staining arising in a background consistent with osteomalacia. After tumour resection, the patient’s hypophosphataemia, reduced TRP and elevated FGF- 23 normalised and he made an excellent recovery with rehabilitation. This case report illustrates the importance of a diagnosis of hypophosphataemia in a patient with musculo-skeletal aches and alerts clinicians of the differential diagnosis of TIO.

A Multifocal Paraganglioma in an African Male Due to an Underlying SDHB Mutation

Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors arising from adrenal and extra-adrenal paraganglia. Up to forty percent are due to an underlying germline mutation. Mutations in the subunit B gene of the SDH complex (SDHB) are associated with PGL syndrome four. A 34-yr-old African man from Southern Africa presented with a two-year history of sustained hypertension associated with the classic triad of sweating, headaches and palpitations. Family history was contributory towards early unexpected deaths of his father (age 42) and two younger brothers (ages 13 and 14 respectively). On examination his blood pressure was persistently elevated measuring 146/87mmHg. In view of the classic presenting symptoms and hypertension onset at a young age, a PPGL was suspected. Biochemical investigations were positive with an elevated 24-hour urine normetanephrine level of 35807 (480-2424nmol/24hours), normal metanephrine level of 689 (264-1729nmol/24hours), an elevated normetanephrine:creatinine ratio of 3270 (28-158nmol/mmol creatinine) and an elevated methoxytyramine level 4941.69nmol/24 hours (<800nmol/24 hours). Computed tomography of the abdomen and neck revealed a homogenous soft tissue mass measuring 5.9cm x 3.6cm x 6.6cm anterior to the right kidney and separate from the right adrenal gland and a carotid body tumor measuring 3.6cm x 2.9cm x 4.1cm. Both were radio-avid on a [68Gallium]-DOTATATE-Positron Emission Tomography (PET)-CT. There were no features to suggest metastatic disease. Genetic testing is not available in South Africa; therefore, testing was done at an international laboratory. This revealed a pathological SDHB mutation variant, c.724C>A p.(Arg242Ser) and hence PGL4 syndrome. The patient underwent staged surgery with successful removal of the intra-abdominal tumor. Unfortunately, due to peri-operative complications associated with the second surgery, the patient demised. Histopathological examination of both tumors was consistent with a paraganglioma. Genetic counselling and testing were offered to all living first-degree relatives. His sister tested positive for the same pathological variant. His 6-week-old son will be offered counselling and testing at a later stage. To the best of our knowledge, we are the first to describe the missense SDHB mutation (pathogenic variant c.724C>A p.[Arg242Ser]) and the occurrence of an SDHB associated PGL in a family of African ethnicity. This case highlights the importance of genetic counselling and testing in patients with a confirmed PPGL. Due to resource limitation the African population remains under represented in genetic studies which limits the utility of precision medicine in this group. As such, our case is an important addition to the body of knowledge in this growing field and highlights the need for cost effective genetic screening tools in low resourced settings.

Predictors of antiproliferative effect of lanreotide autogel in advanced gastroenteropancreatic neuroendocrine neoplasms

PurposeThe antiproliferative properties of lanreotide autogel (LAN) in gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) were demonstrated in the CLARINET study. However, there is limited literature regarding factors that affect progression-free survival (PFS) in patients with GEP NENs treated with LAN.MethodsWe identified a total of 191 treatment-naive patients with advanced GEP NENs and positive SSTR uptake on imaging (Octreoscan or 68Gallium DOTATATE Positron Emission Tomography [68GaPET]) who received first-line LAN monotherapy, albeit at various starting doses (60, 90 or 120 mg/month). A group of 102 patients who initiated treatment at the standard dose of 120 mg/month were included in the study and further evaluated by univariate and multivariate analyses to identify predictors of PFS.ResultsThe location of tumour primary was in the small bowel in 63 (62%), pancreas in 31 (30%) and colon/rectum in 8 patients (8%). The tumours were well-differentiated, and the majority were grade 1 (52%), or 2 (38%). About 60% of cases had progressive disease at the time of treatment initiation. Most patients with available pretreatment nuclear medicine imaging (Octreoscan or 68Ga PET) had a Krenning score of 3 (44%) or 4 (50%). The median PFS for the entire cohort was 19 months (95% CI 12, 26 months). The univariate analysis demonstrated that grade 2 tumours, progressive disease at baseline and metastatic liver disease were associated with a significantly shorter PFS, while other evaluated variables did not affect PFS at a statistically significant level. However, at multivariate analysis only the tumour grade remained statistically significant.ConclusionsThe current study showed that, of many evaluated variables, only the tumour grade was predictive of PFS duration and this should be considered during patient selection for treatment.

The Correlation Between [68Ga]DOTATATE PET/CT and Cell Proliferation in Patients With GEP-NENs.

Objectives of the study are to analyze the correlation between [68Ga]DOTATATE positron emission tomography (PET)/X-ray computed tomography (CT) measurements and various biological characteristics of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), and to determine optimal cutoff value of SUVmax (standard uptake value) to differentiate neuroendocrine tumors (NETs) and neuroendocrine cancers (NECs). Of the GEP-NEN cases (73 males, 53 females; age 18-77years) with pathologically proven primary and/or metastatic lesions, 126 were studied. All of the short axes of lesions were larger than 0.5cm in order to avoid the partial volume effect. Patients fasted for 6h before the PET/CT scans. The dose of [68Ga]DOTATATE was 100-200MBq and the acquisition began at 1h after injection. The lesion with the highest SUVmax in each patient was analyzed. In the total sample, the sensitivity of [68Ga]DOTATATE was 69.05%. The sensitivities were significantly different among G1, G2, and G3 groups (72.22%, 91.53%, and 40.82%, respectively; p < 0.01). The SUVmax of the G3 group was lowest. We also found that the sensitivity and SUVmax were significantly higher (p < 0.05) in patients with pancreatic NENs (Pan-NENs) than in patients with gastrointestinal NENs (Gi-NENs) and unknown primary NENs (Up-NENs). A significant negative correlation between SUVmax and Ki-67 was found (r = - 0.429, p < 0.01). Using SUVmax to differentiate neuroendocrine tumors (NETs) and neuroendocrine cancers (NECs), the area under the ROC curve (AUC) was 0.771 and the cutoff value of SUVmax was 11.25 (sensitivity 79.2%, specificity 65.3%). However, Pan-NENs did not show any statistical significance results in correlation and ROC analysis. [68Ga]DOTATATE PET/CT results showed a negative correlation with GEP-NEN cell proliferation and were complementary to Ki-67. Pan-NENs were different from Gi-NENs and Up-NENs when compared to somatostatin receptor expression.

The role of baseline Ga-68 DOTATATE positron emission tomography/computed tomography in the prediction of response to fixed-dose peptide receptor radionuclide therapy with Lu-177 DOTATATE.

To describe the role of baseline gallium (Ga)-68 DOTATATE positron emission tomography (PET)/computed tomography (CT) in the prediction of the response to peptide receptor radionuclide therapy (PRRT) using lutetium (Lu)-177 DOTATATE. Analysis was made of baseline Ga-68 DOTATATE PET/CT images of 29 patients (17 females and 12 males; mean age: 50.7 ± 14.6 years) with metastatic neuroendocrine tumors who received PRRT with Lu-177 DOTATATE. Maximum standardized uptake values (SUVmax) of reference lesions and their ratios to physiological uptake organs were calculated. The relationship between these values and the radiological response was analyzed. Partial response was observed in 8 (28%) patients, stable disease in 18 (62%) patients, and progressive disease in 3 (10%) patients. Mean SUVmax of reference lesions was calculated as 23.8 ± 20.5 (min-max: 5.1-87.3). There was no significant correlation between radiological responses and SUVmax of reference lesions and their ratios to other organs. Baseline Ga-68 DOTATATE PET/CT helps to show somatostatin receptor expression status and disease stage in patients who are candidates for PRRT. However, SUVs do not have a role in the prediction of treatment response.

Insulinoma Localization by Glucagon-Like Peptide-1 Receptor Imaging After 18 Years of Hypoglycemia

ABSTRACT Objective: Insulinoma is the most frequent cause of hyperinsulinemic hypoglycemia in adults, but its preoperative localization may be challenging. Methods: We report on a patient with a remarkably long history of persistent hypoglycemia due to an insulinoma, which was finally localized after 18 years using glucagon-like peptide-1 receptor (GLP-1R) imaging. Results: The patient was admitted in 1995 for hypoglycemia. A fasting test documented inadequate insulin suppression. She had given birth to a baby who was small for gestational age a few weeks earlier. The patient underwent surgery for a pancreatic tail nodule, which histologically proved to be normal tissue. Hypoglycemia recurred postoperatively. Diazoxide initially controlled symptoms, but over the years, the patient had recurrent hypoglycemic seizures and coma. The patient underwent repeated pancreatic magnetic resonance imaging (MRI), indium-111 (111In)-octreotide scintigraphy, galladium-68 (68Ga)-DOTATATE-positron emission tomography (PET) scan, 18F-DOPA-PET scan and arterial calcium stimulation with hepatic venous sampling; all were negative. Finally, a SPECT-CT with indium-111 diethylene triamine pentaacetic acid (111In-DTPA)-exendin-4, a radioligand with high affinity to the GLP-1R, showed focally increased tracer uptake in the pancreas tail. Endoscopic ultrasound (US) and fine-needle aspiration confirmed the endocrine origin of the tumor. The patient underwent laparoscopic tail pancreatectomy and was cured after 18 years of hyper-insulinemic hypoglycemia. Ex vivo studies of the insulinoma confirmed elevated insulin secretion at low glucose concentrations and abundant GLP-1R expression. Conclusion: GLP-1R imaging is a highly valuable tool in the localization of insulinoma when other conventional methods fail to identify the tumor. This new imaging tool will enable timely localization and cure for insulinoma patients. Abbreviations: ASVS selective arterial calcium stimulation and hepatic venous sampling 11C carbon 11 CT computed tomography DTPA diethylene triamine penta-acetic acid 18F-DOPA 18F-3,4-dihydroxyphenylalanine GLP-1R glucagonlike peptide-1 receptor 111In indium-111 KATP channels adenosine triphosphate-sensitive potassium channels MRI magnetic resonance imaging PET positron emission tomography SPECT single-photon-emission computed tomography SST2R somatostatin receptor type 2 SST5R somatostatin receptor type 5 US ultrasound

Lutetium DOTATATE whole body scans: A novel approach for evaluation of neuroendocrine tumors

Aim:We undertook a study to evaluate whether Lutetium (Lu) DOTATATE whole body scan is well comparable to Gallium positron emission tomography (PET) / Indium Octreotide, and hence with dosimetric advantage can replace it in the pre-therapy setting.Materials and Methods:We undertook a prospective study of a total of 39 patients with metastatic neuroendocrine tumor (age 11–70 years), who underwent Lu-DOTATATE scans within the period August 2009–November 2010. This included 28 males and 11 females. Dose of Lu-DOTATATE injected for diagnostic scanning purpose was 10 mCi i.v. Whole body planar images and single-photon emission computed tomography (SPECT)-CT images were obtained at 4, 24 and 48 hours. The Lu-DOTATATE whole body and SPECT-CT images were compared to contrast CT scans in all patients, and Indium Octreotide and Gallium DOTATATE PET images in nine patients, with reference to detection sensitivity of number of lesions. The pre-therapy scans were also used for dosimetric calculations. Fourteen of these 39 patients further went ahead with Lu-DOTATATE therapy.Results:All 39 patients demonstrated Lu-DOTATATE uptake in the disease sites seen on the contrast CT images. The uptake intensity was well comparable to Indium Octreotide and Gallium DOTATATE PET scans of all nine patients, with equally well-defined lesions. The post-therapy Lu-DOTATATE scans of the 14 patients who underwent therapy demonstrated higher intensity uptake pattern in the same disease sites, suggesting favorable therapeutic effect. The scans were useful in determining dosimetric details for therapeutic purpose and adequate exposure rates to suggest good ablative effect.Conclusion:Our preliminary data suggest that Lu-DOTATATE whole body scanning procedure is cost effective and equally sensitive as Gallium DOTATOC/NOC PET scan in pre-therapy setting of neuroendocrine tumors. The additional advantage of dosimetry calculations on this scanning procedure makes it more ideal to tailor therapies with more accuracy.