Somatostatin Receptor Positron Emission Research Articles

Surgical management of pancreatic neuroendocrine liver metastases.

Pancreatic neuroendocrine tumors (PNET) are a heterogeneous group of neoplasms that vary in their clinical presentation, behavior and prognosis. The most common site of metastasis is the liver. Surgical resection of neuroendocrine liver metastases (NELM) is thought to afford the best long-term outcomes when feasible. Initial preoperative workup should include surveillance for carcinoid syndrome, screening for evidence of liver insufficiency, and performance of imaging specific to neuroendocrine tumors such as a somatostatin receptor positron emission tomography scan. Standard surgical principles apply to hepatic surgery for NELM, namely prioritizing low central venous pressure anesthesia, minimizing blood loss, knowledge of liver anatomy, generous use of intraoperative ultrasound, as well as safe parenchymal transection techniques and practices to avoid bile leakage. Knowledge of established prognostic factors may assist with patient selection, which is important for optimizing short- and long-term outcomes of hepatic resection. Adjunct therapies such as concomitant liver ablation are used frequently and are generally safe when used appropriately. For patients with synchronous resectable NELM, resection of the primary either in a staged or combined fashion is recommended. Primary tumor resection in the setting of unresectable metastatic disease is more controversial, however generally recommended if morbidity is acceptable. For patients who are not surgical candidates, due to either patient performance status or burden of liver disease, several liver-directed therapies such as transarterial embolization, chemoembolization, and radioembolization are available to assist with locoregional control, extend progression-free survival (PFS), and improve symptoms of carcinoid syndrome. Multiple systemic therapy options exist for patients with metastatic PNET which are often prioritized for those patients with advanced or progressive disease. A systematic approach in a multi-disciplinary setting is likely to result in the best long-term outcomes for patients with pancreatic NELM. Ongoing research is needed to determine the optimal patient selection for hepatic surgery as well as the ideal treatment sequencing for those patients with NELM.

Detection Rate of Culprit Tumors Causing Osteomalacia Using Somatostatin Receptor PET/CT: Systematic Review and Meta-Analysis.

Background: Tumor-induced or oncogenic osteomalacia (TIO) is a rare paraneoplastic syndrome in which osteomalacia is a consequence of fibroblast growth factor 23 (FGF23) secretion by a mesenchymal tumor. The localization of the culprit lesion in patients with TIO is often challenging. Several studies have evaluated the detection rate (DR) of these tumors using somatostatin receptor positron emission tomography (SSTR-PET/CT). We aimed to summarize literature findings on this topic providing pooled estimates of DR. Methods: A comprehensive literature search by screening PubMed, Embase and Cochrane library electronic databases through August 2019 was performed. The pooled DR of culprit tumors using SSTR-PET/CT in patients with TIO was calculated using a random-effects statistical model. Results: Fourteen studies on the use of SSTR-PET/CT in detecting the culprit tumor in patients with TIO were included in the qualitative analysis. The pooled DR of SSTR-PET/CT on a per-patient-based analysis calculated using eleven studies (166 patients) was 87.6% (95% confidence interval (95% CI) 80.2–95.1%). Statistical heterogeneity among studies was detected (I-square = 63%), likely due to the use of different radiolabeled somatostatin analogues, as demonstrated by a subgroup analysis. Conclusions: Despite limited literature data due to the rarity of the disease, SSTR-PET/CT demonstrated a very high DR of culprit tumors in patients with TIO and it could be used as first-line imaging method for this indication.

Correlation of DOTATOC Uptake and Pathologic Grade in Neuroendocrine Tumors.

Gallium (Ga)-DOTATOC is a somatostatin analog used to detect neuroendocrine tumors (NETs). Ki-67 proliferation index (Ki-67 PI) has been established as a prognostic factor in NETs. We aimed to evaluate whether a correlation exists between Ki-67 PI and somatostatin receptor positron emission tomography (SSTR-PET) uptake. We retrospectively reviewed 238 DOTATOC PET scans between 2014 and 2016. Patients were excluded if DOTATOC PET was performed more than 365 days from the date of biopsy. Maximum standardized uptake values (SUVmax) of SSTR-PET from biopsied lesions were measured and correlated with Ki-67 PI using the Pearson correlation coefficient. Among 110 lesions from 90 patients, DOTATOC PET had 92.7% sensitivity and 100% specificity (102 true positives, 8 false negatives) for detection of NETs. Among 63 lesions from 54 patients with Ki-67 PI available, there were 27 grade 1 lesions [median Ki-67 PI, 1.0%; interquartile range (IQR), 1.0-2.0], 30 grade 2 lesions (median, Ki-67 PI 7.5%; IQR, 5-10), and 6 grade 3 lesions (median Ki-67 PI, 30%; IQR, 26-34). There was a correlation between Ki-67 PI and SUVmax (r = -0.3, P = 0.018). Our analysis demonstrates an inverse correlation between Ki-67 PI and SUVmax in NETs. Somatostatin receptor-PET provides additional information that can help guide management of NETs.

Detection rate of unknown primary tumour by using somatostatin receptor PET/CT in patients with metastatic neuroendocrine tumours: a meta-analysis.

The high diagnostic performance of somatostatin receptor positron emission tomography with computed tomography (PET/CT) in neuroendocrine tumours (NETs) was demonstrated by several articles. However, only some studies evaluated the detection rate (DR) of this imaging method in patients with metastatic NETs and unknown primary tumours (CUP-NETs). Therefore, we aimed to perform a meta-analysis to add evidence-based data in this setting. A comprehensive computer literature search of studies listed in PubMed/MEDLINE, EMBASE, and Cochrane library databases through December 2018 and regarding the use of somatostatin receptor PET/CT in patients with CUP-NETs was carried out. Pooled DR of CUP-NETs by using somatostatin receptor PET/CT was calculated. A pooled analysis evaluating the percentage of change of management by using somatostatin receptor PET/CT in these patients was also performed. Twelve studies on the use of somatostatin receptor PET/CT in detecting CUP-NETs in 383 metastatic patients were included. The meta-analysis of all these studies provided the following DR on a per patient-based analysis: 56% (95% confidence interval (95% CI): 48-63%). Moderate heterogeneity among the selected studies was found (I2 = 50%), whereas a significant publication bias was excluded by Egger's test (p = 0.45). The most common primary tumour sites were the bowel and the pancreas. A change of management by using somatostatin receptor PET/CT was demonstrated in 20% (95% CI: 10-33%) of patients with CUP-NET. Somatostatin receptor PET/CT is very useful in detecting CUP-NETs in patients with metastatic disease. More studies on the change of management by using this imaging method in this setting are needed.

SUN-394 A Curious Case of Cushing's

Background: Cushing’s Disease and Syndrome is a rare condition that can greatly impact a person’s health. Usually, it is easy to determine the cause of cortisol excess. However, when adrenal and pituitary examination fail to reveal a source, devising a management strategy can prove difficult. Clinical Case: A 27-year-old male with no significant PMH presented originally to an urgent care clinic with non-specific complaints, gaining weight, back spasms weakness, and chest pain. He was hypertensive and had significant abdominal stria. He was referred to endocrinology and found to be very cushingoid. Initial laboratory testing found a random cortisol 29.3 mcg/dl and ACTH was 227.4 pg/ml. Salivary cortisol was elevated at 0.526 ug/dl. A 24 hour urinary cortisol was 800 ug/24 hours. An 8mg dexamethasone suppression test was performed which did not suppress cortisol (22.2 mcg/dl). An MRI of his pituitary was read as normal. A chest CT showed a healed 2nd rib fracture but otherwise unremarkable. CT of abdomen and pelvis showed no adrenal mass and demineralization of the bone especially at the spine. The patient then underwent inferior petrosal sinus sampling which showed no step up from peripheral to central. At this point the he was started on Ketoconazole which was titrated up to 800mg mg/day. The patient was subsequently admitted multiple times to the hospital for cellulitis of his lower left extremity. A skin biopsy of his lower extremity revealed erythema nodosum. During one of these admissions he developed adrenal insufficiency which was treated with hydrocortisone replacement. Gallium-68 somatostatin receptor positron emission tomography was performed to determine the source of ACTH. It revealed a nonspecific subcentimeter nodular focus of tracer uptake just lateral to the right atrial appendage. Since being on the ketoconazole the patient has experienced significant improvement in his blood pressure, strength and abdominal striae. Conclusion: This unusual case provides valuable insight into the process of diagnosing Cushing’s Disease and Syndrome. While this process is usually straight forward, if an ectopic source of elevated ACTH remains unknown, the case can require a very substantial investigation. Because of the unique complexity of this case, it allows for a useful review of the physiology and pathophysiology of the pituitary adrenal axis.

Detection rate of somatostatin receptor PET in patients with recurrent medullary thyroid carcinoma: a systematic review and a meta-analysis.

Several articles have demonstrated the high diagnostic performance of somatostatin receptor positron emission tomography (PET) in patients with neuroendocrine tumours (NETs). On the other hand, only a few studies have evaluated the detection rate (DR) of this imaging method in recurrent medullary thyroid carcinoma (MTC). We aimed to perform a systematic review and a meta-analysis of the DR of somatostatin receptor PET or PET/CT in patients with recurrent MTC to add evidence-based data to this setting. A comprehensive computer literature search of studies published in PubMed/MEDLINE and the Cochrane Library Database through May 2017 and regarding somatostatin receptor PET or PET/CT in patients with recurrent MTC was carried out. DR was determined on a per patient-basis. A sub-analysis considering serum calcitonin (Ctn) values was also performed. Nine studies on the diagnostic performance of somatostatin receptor PET or PET/CT in detecting recurrent MTC were discussed in the systematic review. The meta-analysis of these selected studies provided the following DR on a per patient-based analysis: 63.5% [95% confidence interval (95%CI): 49-77]. Heterogeneity among the selected studies was found. DR of somatostatin receptor PET or PET/CT increased in patients with higher serum Ctn levels (83% for Ctn >500 ng/L). In patients with recurrent MTC, somatostatin receptor PET or PET/CT demonstrated a non-optimal DR which increased in patients with higher serum Ctn values. The diagnostic performance of somatostatin receptor PET or PET/CT in recurrent MTC is lower compared to that of the same imaging method in the majority of NETs.

Cardiovascular magnetic resonance imaging and clinical performance of somatostatin receptor positron emission tomography in cardiac sarcoidosis.

AimsCardiac affection constitutes a major limiting condition in systemic sarcoidosis. The primary objective of this study was to investigate the persistence rate of cardiac sarcoid involvement by cardiovascular magnetic resonance (CMR) imaging in patients diagnosed with cardiac sarcoidosis (CS). Moreover, we examined the additional insights into myocardial damage's characteristics gained by somatostatin receptor scintigraphy.Methods and resultsIn a pilot study, we had previously identified cardiac involvement—diagnosed by CMR imaging—to be present in 29 of 188 patients (15.4%) with histologically proven, extra‐CS. Out of these initial 29 CS‐positive patients, 27 patients (49.9 ± 11.8 years, 59.3% male) were presently re‐examined and underwent a second CMR study and complementary standard clinical testing. Somatostatin receptor scintigraphy using the ligand 68Ga‐DOTATOC was additionally performed when clinically indicated (17 patients). Within a median follow‐up period of 2.6 years, none of the initial 29 patients deceased or experienced aborted sudden cardiac death. However, two patients developed third‐degree atrioventricular block that required device therapy. Among the 27 re‐examined CS patients, pathological CMR findings persisted in 14 of 27 patients (51.9%). CS remission was primarily due to a resolution of acute inflammatory processes. 68Ga‐DOTATOC positron emission tomography/computed tomography (PET/CT) identified one patient with regions of raised tracer uptake that concorded with acute inflammatory changes, as assessed by CMR; this patient received no immunosuppressive medication at the time of PET/CT execution.ConclusionsWithin follow‐up, CS persisted in barely half the patients, and the patients were not afflicted with cardiac death. Additional 68Ga‐DOTATOC PET/CT allowed for visualization of acute myocardial inflammation.

Appropriate Use Criteria for Somatostatin Receptor PET Imaging in Neuroendocrine Tumors.

Somatostatin receptor positron emission tomography (SSTR-PET) is an imaging modality for patients with neuroendocrine tumors (NETs) that has demonstrated a significant improvement over conventional imaging (CI). SSTR-PET should replace In-111 pentetreotide scintigraphy (OctreoScan) in all indications in which SSTR scintigraphy is currently being used. These appropriate use criteria (AUC) are intended to aid referring medical practitioners in the appropriate use of SSTR-PET for imaging of patients with NETs, and the indications were evaluated in well-differentiated NETs. Of the 12 clinical scenarios evaluated, nine were graded as appropriate: initial staging after the histologic diagnosis of NET, evaluation of an unknown primary, evaluation of a mass suggestive of NET not amenable to endoscopic or percutaneous biopsy, staging of NET prior to planned surgery, monitoring of NET seen predominantly on SSTR-PET, evaluation of patients with biochemical evidence and symptoms of a NET, evaluation of patients with biochemical evidence of a NET without evidence on CI or a prior histologic diagnosis, restaging at time of clinical or laboratory progression without progression on CI, and new indeterminate lesion on CI with unclear progression. Representatives from the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the American College of Radiology (ACR), the American Society of Clinical Oncology (ASCO), the North American Neuroendocrine Tumor Society (NANETS), the European Association of Nuclear Medicine (EANM), the Endocrine Society, the Society of Surgical Oncology, the National Comprehensive Cancer Network (NCCN), the American College of Physicians (ACP), the American Gastroenterological Association (AGA), and the World Conference on Interventional Oncology (WCIO) assembled under the auspices of an autonomous workgroup to develop the following AUC.

Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging

BackgroundInflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG PET), [18F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover. ObjectivesThis study tested the efficacy of gallium-68-labeled DOTATATE (68Ga-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for imaging atherosclerotic inflammation. MethodsWe confirmed 68Ga-DOTATATE binding in macrophages and excised carotid plaques. 68Ga-DOTATATE PET imaging was compared to [18F]FDG PET imaging in 42 patients with atherosclerosis. ResultsTarget SSTR2 gene expression occurred exclusively in “proinflammatory” M1 macrophages, specific 68Ga-DOTATATE ligand binding to SST2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo 68Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). 68Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBRmax) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome (median difference: 0.69; interquartile range [IQR]: 0.22 to 1.15; p = 0.008) and transient ischemic attack/stroke (median difference: 0.13; IQR: 0.07 to 0.32; p = 0.003). 68Ga-DOTATATE mTBRmax predicted high-risk coronary computed tomography features (receiver operating characteristics area under the curve [ROC AUC]: 0.86; 95% CI: 0.80 to 0.92; p < 0.0001), and correlated with Framingham risk score (r = 0.53; 95% CI: 0.32 to 0.69; p <0.0001) and [18F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [18F]FDG mTBRmax differentiated culprit from nonculprit carotid lesions (median difference: 0.12; IQR: 0.0 to 0.23; p = 0.008) and high-risk from lower-risk coronary arteries (ROC AUC: 0.76; 95% CI: 0.62 to 0.91; p = 0.002); however, myocardial [18F]FDG spillover rendered coronary [18F]FDG scans uninterpretable in 27 patients (64%). Coronary 68Ga-DOTATATE PET scans were readable in all patients. ConclusionsWe validated 68Ga-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that 68Ga-DOTATATE offers superior coronary imaging, excellent macrophage specificity, and better power to discriminate high-risk versus low-risk coronary lesions than [18F]FDG. (Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography [VISION]; NCT02021188)

Initial Clinical Experience with 68Ga-DOTA-NOC Prepared Using 68Ga from Nanoceria-polyacrylonitrile Composite Sorbent-based 68Ge/68Ga Generator and Freeze-dried DOTA-NOC Kits.

Somatostatin receptor positron emission tomography–computed tomography (PET/CT) with 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) peptides have become an indispensable part of disease assessment in patients with neuroendocrine tumors and forms the basis of personalized therapy with peptide receptor-based radionuclide therapy. With growing utilization of PET/CT in developing countries, availability of the indigenous GMP-certified 68Ge/68Ga generators is expected to further promote cost-effective molecular imaging service to the cancer patients. We present our initial clinical experience in 32 patients injected with 68Ga-DOTA-NOC prepared using 68Ga eluted from Bhabha Atomic Research Centre nanoceria-polyacrylonitrile sorbent-based 68Ge/68Ga generator and freeze-dried DOTA-NOC cold kits.

Preliminary PET/CT Imaging with Somatostatin Analogs [68Ga]DOTAGA-TATE and [68Ga]DOTAGA-TOC.

Somatostatin receptor positron emission tomography/X-ray computed tomography (SSTR-PET/CT) is a well-established technique for staging and detection of neuroendocrine tumors (NETs). Ga-68-labeled DOTA-conjugated octreotide analogs are the privileged radiotracers for diagnosis and therapeutic monitoring of NETs. Hence, we were interested in assessing the influence of promising, newer variant DOTAGA on the hydrophilicity, pharmacokinetics, and lesion pick-up of somatostatin analogs. Herein, the potential of ([68Ga]DOTAGA, Tyr3, Thr8) octreotide ([68Ga]DOTAGA-TATE) and ([68Ga]DOTAGA, Tyr3) octreotide ([68Ga]DOTAGA-TOC) as NET imaging agents has been investigated. Amenability of [68Ga]DOTAGA-(TATE/TOC) to kit-type formulation has been demonstrated. Biodistribution studies were carried out in normal rats at 1h post-injection (p.i.). [68Ga]DOTAGA-(TATE/TOC) PET/CT scans were carried out in patients (70-170MBq, 1h p.i.) with histologically confirmed well-differentiated NETs. [68Ga]DOTAGA-TATE exhibited hydrophilicity similar to [68Ga]DOTA-TATE (log P=-3.51 vs -3.69) whereas [68Ga]DOTAGA-TOC was more hydrophilic than [68Ga]DOTA-TOC (log P=-3.27 vs -2.93). [68Ga]DOTAGA-TATE and [68Ga]DOTA-TATE showed almost identical blood and kidney uptake in normal rats whereas significantly fast clearance (p<0.05) of [68Ga]DOTAGA-TATE was observed from other non-specific organs (liver, lungs, spleen, intestine). [68Ga]DOTAGA-TOC also demonstrated rapid clearance from blood and kidneys (p<0.05) in comparison to [68Ga]DOTA-TOC. The metastatic lesions in NET patients were well identified by [68Ga]DOTAGA-TATE and [68Ga]DOTAGA-TOC. The phenomenal analogy was observed between [68Ga]DOTAGA-TATE and [68Ga]DOTA-TATE as well as between [68Ga]DOTAGA-TOC and [68Ga]DOTA-TOC in biodistribution studies in rats. The good lesion detection ability of the two radiotracers indicates their potential as NET imaging radiotracers.

Somatostatin receptor positron emission tomography/computed tomography imaging in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is an uncommon aggressive primary cutaneous carcinoma with neuroendocrine differentiation. However, literature data about the use of somatostatin receptor positron emission tomography/computed tomography (PET/CT) imaging in MCC are limited and its role is not clearly stated. To investigate the role of PET/CT using somatostatin analogues radiolabelled with gallium-68 in patients with MCC. All patients affected by MCC who performed a somatostatin receptor PET/CT imaging from October 2007 to May 2014 were retrospectively analysed. The diagnostic performances of PET/CT were evaluated on a patient-based analysis and compared to final diagnosis (histology = 3 or clinical/radiological follow-up = 20). We evaluated 23 consecutive MCC patients [18 men; median age 71 years (range 47-87)]. Primary tumour was located in ear (1/23), cheek (3/23), arm (2/23), hand (1/23), back (1/23), anal canal (1/23), gluteus (4/23), thigh (3/23) and popliteal fossa (1/23). In 6/23 patients, the site of primary tumour was unknown. PET/CT was performed to detect primary tumour site (4/23) or to stage (8/23) or re-stage (11/23) patients. PET/CT resulted positive in 14/23 patients and according to the final diagnosis was defined true positive, true negative, false positive (FP) and false negative in 11/23, 8/23, 3/23 and 1/23 cases respectively. FP PET/CT results were due to unspecific liver uptake, post-surgical inflammation and pancreatic neuroendocrine tumour. PET/CT was unable to detect primary tumour site in all patients with unknown primary MCC. Sensitivity, specificity and diagnostic accuracy of PET/CT were 92%, 73% and 83% respectively. In our experience, somatostatin receptor PET/CT imaging resulted useful in patients with MCC and presented high diagnostic performances with a significant impact in disease management although in patients with unknown primary MCC, it was unable to identify the primary tumour site.

Bedeutung der PET/CT für die Chirurgie neuroendokriner Neoplasien

Neuroendocrine neoplasms (NEN) are rare malignancies with a wide spectrum of metastatic potential which originate from the endocrine cells of the body and express somatostatin receptors. The (68)gallium somatostatin receptor positron emission tomography-computed tomography (PET/CT) technique is the most sensitive method of assessment of well-differentiated NENs and for the detection of cancer of unknown primary (CUP syndrome) NENs. Imaging with 18F-fluorodeoxyglucose (18F-FDG PET/CT) is indicated in poorly differentiated neuroendocrine carcinomas. The receptor-dependent imaging of NENs has a decisive impact on further management.

Diagnostic role of Gallium-68 DOTATOC and Gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis

Gallium-68 somatostatin receptor positron emission tomography (PET) has been used in the diagnosis of neuroendocrine tumors (NETs). The compounds often used in molecular imaging of NETs with PET are 68Ga-DOTATOC, 68Ga-DOTATATE, and 68Ga-DOTANOC. There is varying affinity to different somatostatin receptors. To systematically review and perform a meta-analysis of published data regarding the diagnostic role of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs. A comprehensive literature search of studies published through 30 April 2013 regarding 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs was performed using the PubMed/MEDLINE, Embase, and Scopus databases. Pooled sensitivity and specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs. Ten studies comprising 416 patients with NETs were included in this meta-analysis. The pooled sensitivity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs calculated on a per-patient-based analysis was 93% (95% confidence interval [CI] 89-96%) and 96% (95% CI 91-99%). The pooled specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in diagnosing NETs was 85% (95% CI 74-93%) and 100% (95% CI 82-100%). The area under the ROC curve of 68Ga-DOTATOC and 68Ga-DOTATATE PET was 0.96 and 0.98, respectively, on a per-patient-based analysis. The molecular imaging agents 68Ga-DOTATOC and 68Ga-DOTATATE demonstrated high sensitivity and specificity in the diagnosis of NETs on PET scan. Although both are accurate tools in the diagnosis of NETs, 68Ga-DOTATATE PET may be more sensitive and specific than 68Ga-DOTATOC PET scan.

Improving Diagnosis of Tumor-Induced Osteomalacia With Gallium-68 DOTATATE PET/CT

Tumor-induced osteomalacia (TIO) is a rarely diagnosed disorder presenting with bone pain, fractures, muscle weakness, and moderate-to-severe hypophosphatemia resulting from fibroblast growth factor 23-mediated renal phosphate wasting. Tumors secreting fibroblast growth factor 23 are often small and difficult to find with conventional imaging. We studied the utility of (68)Ga-DOTA-octreotate (DOTATATE) somatostatin receptor positron emission tomography (PET)/computed tomography (CT) imaging in the diagnosis of TIO. A multicenter case series was conducted at tertiary referral hospitals. Six patients with TIO diagnosed between 2003 and 2012 in Australia were referred for DOTATATE PET imaging. We reviewed the clinical history, biochemistry, imaging characteristics, histopathology, and clinical outcome of each patient. Each case demonstrated delayed diagnosis despite severe symptoms. DOTATATE PET/CT imaging demonstrated high uptake and localized the tumor with confidence in each case. After surgical excision, there was resolution of clinical symptoms and serum phosphate, except in one patient who demonstrated residual disease on PET/CT. All tumors demonstrated high somatostatin receptor subtype 2 cell surface receptor expression using immunohistochemistry. In patients with TIO, DOTATATE PET/CT can successfully localize phosphaturic mesenchymal tumors and may be a practical first step in functional imaging for this disorder. Serum phosphate should be measured routinely in patients with unexplained muscle weakness, bone pain, or stress fractures to allow earlier diagnosis of TIO.

Somatostatin receptor positron emission tomography/computed tomography (PET/CT) in the evaluation of opsoclonus-myoclonus ataxia syndrome

Opsoclonus-myoclonus ataxia (OMA) syndrome is the most common paraneoplastic neurological syndrome of childhood, associated with occult neuroblastoma in 20%-50% of all cases. OMA is the initial presentation of neuroblastoma in 1%-3% of children. Conventional radiological imaging approaches include chest radiography and abdominal computed tomography (CT). Nuclear medicine techniques, in form of 123I/131I-metaiodobenzylguanidine (MIBG) scintigraphy have been incorporated in various diagnostic algorithms for evaluation of OMA. We describe use of somatostatin receptor PET/CT with 68Gallium- DOTA-DPhe1, Tyr3-octreotate (DOTATATE) in diagnosis of neuroblastoma in two cases of OMA.

Diagnostic performance of Gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis

Gallium-68 somatostatin receptor (SMSR) positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) are valuable diagnostic tools for patients with neuroendocrine tumours (NETs). To date, a meta-analysis about the diagnostic accuracy of these imaging methods is lacking. Aim of our study is to meta-analyse published data about the diagnostic performance of SMSR PET or PET/CT in patients with thoracic and/or gastroenteropancreatic (GEP) NETs. A comprehensive computer literature search of studies published in PubMed/MEDLINE, Scopus and Embase databases through October 2011 and regarding SMSR PET or PET/CT in patients with NETs was carried out. Only studies in which SMSR PET or PET/CT were performed in patients with thoracic and/or GEP NETs were selected (medullary thyroid tumours and neural crest derived tumours were excluded from the analysis). Pooled sensitivity, pooled specificity and area under the ROC curve were calculated to measure the diagnostic accuracy of SMSR PET and PET/CT in NETs. Sixteen studies comprising 567 patients were included in this meta-analysis. The pooled sensitivity and specificity of SMSR PET or PET/CT in detecting NETs were 93% (95% confidence interval [95% CI]: 91-95%) and 91% (95% CI: 82-97%), respectively, on a per patient-based analysis. The area under the ROC curve was 0.96. In patients with suspicious thoracic and/or GEP NETs, SMSR PET and PET/CT demonstrated high sensitivity and specificity. These accurate techniques should be considered as first-line diagnostic imaging methods in patients with suspicious thoracic and/or GEP NETs.

Cost comparison of 111In-DTPA-octreotide scintigraphy and 68Ga-DOTATOC PET/CT for staging enteropancreatic neuroendocrine tumours

Although somatostatin receptor positron emission tomography (PET)/CT is gaining increasing popularity and has shown its diagnostic superiority in several studies, (111)In-diethylenetriaminepentaacetic acid (DTPA)-octreotide is still the current standard for diagnosis of neuroendocrine tumours (NET). The aim of this study was to compare the costs for the two diagnostic tests and the respective consequential costs. From January 2009 to July 2009, 51 consecutive patients with enteropancreatic NET who underwent contrast-enhanced (68)Ga-DOTATOC PET/CT (n = 29) or (111)In-DTPA-octreotide (mean 3 whole-body scans plus 1.6 low-dose single photon emission computed tomography/CT; n = 22) were included. For cost analysis, direct costs (equipment) and variable costs (material, labour) per examination were calculated. Additionally required CT and/or MRI examinations within the staging process were assessed as consequential costs. An additional deterministic sensitivity analysis was performed. A (68)Ga-DOTATOC PET/CT examination yielded total costs (equipment, personnel and material costs) of 548 euro. On the other hand, an (111)In-DTPA-octreotide examination resulted in 827 euro total costs. Costs for equipment and material had a share of 460 euro/720 euro for (68)Ga-DOTATOC/(111)In-DTPA-octreotide and labour costs of 89 euro/106 euro. With (68)Ga-DOTATOC additional MRI had to be performed in 7% of the patients resulting in a mean of 20 euro for supplementary imaging per patient; 82% of patients with (111)In-DTPA-octreotide needed additional MRI and/or CT resulting in mean additional costs of 161 euro per patient. (68)Ga-DOTATOC PET/CT was considerably cheaper than (111)In-DTPA-octreotide with respect to both material and personnel costs. Furthermore, by using (68)Ga-DOTATOC PET/CT considerably fewer additional examinations were needed reducing the consequential costs significantly.

Concomitant lung and gastroenteropancreatic neuroendocrine tumors and the value of gallium-68 PET/CT

Well-differentiated neuroendocrine tumors (NETs) of the lung occur as typical and atypical carcinoids. Little is known about the biology of these tumors in respect of their ability to metastasize or the probability of development of concomitant neuroendocrine tumors. Here we report a patient diagnosed with a second neuroendocrine tumor of the ileum 4 years after curative resection of a typical carcinoid of the left lung. The intestinal neuroendocrine tumor was successfully detected by gallium-68 based somatostatin receptor positron emission tomography (PET)/computed tomography (CT) and surgically removed using gamma probe detection based on the same labeling. This case report underlines the utility of somatostatin receptor PET/CT based detection and follow-up of NETs.

6-[F-18]Fluoro-l-DOPA Positron Emission Tomography in the Imaging of Merkel Cell Carcinoma: Preliminary Report of Three Cases with 2-Deoxy-2-[F-18]Fluoro-d-Glucose Positron Emission Tomography or Pentetreotide-(111In) SPECT Data

Merkel cell carcinoma (MCC) is an uncommon and aggressive cutaneous neoplasm of neuroendocrine origin. Somatostatin receptor scintigraphy (SRS) and positron emission tomography (PET) using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) have been proposed to stage MCC and to detect early recurrences. As 6-[F-18]fluoro-L-DOPA (FDOPA) is taken up by other neuroendocrine tumors, we speculated that FDOPA-PET could image MCC. FDOPA-PET was performed together with FDG-PET (three patients) and SRS (two patients) in different clinical settings: localization of the primary tumor, staging, and suspicion of recurrence. Uptake of FDOPA-(18F) by MCC was observed in the two true-positive cases, with an agreement between the results of FDOPA-PET, FDG-PET, and SRS; however, the contrast was lower on FDOPA-PET than on FDG-PET images. In the last patient suspected of recurrence repeatedly on SRS and with inconclusive FDG-PET, FDOPA-PET was negative, and a 12-month follow-up demonstrated a true-negative result. MCC takes up FDOPA-(18F). The potential role of FDOPA-PET in its management warrants clarification.