Detection Of Neuroendocrine Tumors Research Articles

Contribution of 111In-pentetreotide SPECT/CT imaging to conventional somatostatin receptor scintigraphy in the detection of neuroendocrine tumours

The aim of the study was to assess the contribution of 111In-pentetreotide single-photon emission computed tomography/computed tomography (SPECT/CT) imaging to conventional somatostatin receptor scintigraphy (SRS) in terms of lesion characterization and localization in the detection of neuroendocrine tumours (NETs). A total of 107 patients with suspected or confirmed NET underwent SRS and SPECT/CT after the injection of 148-222 MBq of 111In-pentetreotide. SRS and SPECT/CT images were interpreted independently. Each site of abnormal tracer uptake was recorded according to the anatomical localization, and as being consistent or not with NET. The findings were confirmed with pathological and/or clinical/imaging follow-up data. A final diagnosis of NET was achieved in 49/107 patients (45.8%). No evidence of NET was found in the rest. SPECT/CT resulted in a significant reduction of indeterminate cases [14/107 (13.1%) vs. 1/107 (0.9%); P<0.001] and correctly reclassified one patient as negative for NET and another as positive for NET. SPECT/CT had 87.8% sensitivity and 96.6% specificity on a patient-based analysis, statistically higher than SRS (P<0.001). A total of 160 foci were detected (108 NETs and 52 physiological/benign tumours). SRS correctly classified 105/160 foci (65.6%) and remained inaccurate for 55 lesions. These 55 included 31 indeterminate lesions, 12 lesions detected only by SPECT/CT and 12 false-positive lesions. The number of foci correctly classified on the SPECT/CT images was 151/160 (94.4%), whereas two remained indeterminate and seven were false-positive findings. SPECT/CT provides incremental diagnostic value over SRS, mainly because of a precise anatomical localization that helps discriminate between tumour lesions and physiological uptake. SPECT/CT may detect unsuspected lesions in a small proportion of patients.

Accuracy of Diagnosing PDA, Neuroendocrine Tumors, and IPMN by EUS-FNA at a Single Institution

Background: The purpose of this study was to assess the clinical impact of diagnostic accuracy for EUS-FNA in evaluating pancreatic lesions, particularly Pancreatic Ductal Adenocarcinoma( PDAC), neuroendocrine tumors, and IPMN at our institution using surgical pathological review as the gold standard. Methods: We conducted a retrospective chart review using the Clinical Cancer Research Database at Huntsman Cancer Institute. We included all cases in which pancreatic lesions were evaluated by EUS-FNA and a subsequent surgical resection was performed. Sensitivity, specificity, positive predicative value (PPV), and negative predictive value (NPV) were determined for PDAC, neuroendocrine tumors, and IPMN by comparing pathological diagnosis at EUS-FNA to diagnoses following surgery. Results: Detection of PDAC by FNA-EUS yielded 87.9% (80.1-93.4 95% CI) sensitivity, 80% (72-86) specificity, 78% (70-85) PPV, and 89% (82-94) NPV. Detection of neuroendocrine tumors by FNA-EUS yielded 66% (47-87) sensitivity, 100% (97-100) specificity, 94% (71-99) PPV, and 97% (94-99) NPV. Detection of IPMN by FNA-EUS yielded 59% (43-74) sensitivity, 100% (98-100) specificity, 100% (87-100) PPV, and 89% (93-99) NPV. Conclusions: Our findings are largely consistent with the current literature, confirming there is discernible potential for inappropriate treatment of patients based purely on EUS-FNA evaluation. Both accuracy and clarity of positive tests with EUS-FNA worsened for mucinous pancreatic lesions compared to solid pancreatic lesions. Limitations of this study are the appraisal at a single institution and the necessity to evaluate only cases that ultimately had surgical resection of the pancreatic lesion.

Diagnostic accuracy of bronchial brush cytology and the added value of immunohistochemistry and fluorescence in situ hybridization of pulmonary neuroendocrine tumors.

Background:Bronchial brush (BB) cytology carries low sensitivity for detecting neuroendocrine carcinomas (NECs), including typical carcinoid (TC) tumors of the lung. We aimed to investigate the detection of neuroendocrine tumors including TC through BB routine cytology cell block (CB), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH).Materials and Methods:A SNOMED search showed 187 lung biopsy or resection specimens from 2008 through 2011 containing neuroendocrine or carcinoid in the diagnosis. Residual BB specimens retained in PreservCyt were used to prepare a ThinPrep slide for FISH analysis. CBs were stained with H and E and IHC for chromogranin and synaptophysin.Results:Of the 187 cases, 16 had residual BB material available within 1 year of diagnosis and were used in CB preparation for IHC and FISH slides. Cytologic evaluation determined 1 case positive for malignancy (small cell lung carcinoma [SCLC]), 1 suspicious for adenocarcinoma, and 14 negative for malignancy. On the basis of histologic diagnosis, FISH was performed. SCLC showed polysomy (86% abnormal cells); 2 TC tumors showed a gain of 7p12 (15% abnormal cells) and a gain of 5q15 (72% abnormal cells), respectively. Two cases had CBs with positive immunoreactivity for chromogranin and synaptophysin. The sensitivity for detection of NEC was 18.8%, 15.4%, and 25% for cytologic evaluation, CB, and FISH, respectively.Conclusion:Neuroendocrine tumors, including TC are difficult to detect with BB cytologic evaluation, most likely because tumor cells lack in the specimen. Assessment of further studies is needed to explore the role of cytology and ancillary methods for detection of these tumors.

Role of molecular imaging in the detection of neuroendocrine tumour

Neuroendocrine tumours (NETs) have distinct biological and clinical characteristics, in particular a high density of somatostatin receptors at the cell membrane [1]. It is this property that allows the use of radiolabelled somatostatin analogues for imaging of these tumours. Importantly, somatostatin receptor PET/CT imaging (e.g. 68Ga-DOTATOC, 68Ga-DOTATATE, 68Ga-DOTANOC) is superior to somatostatin receptor scintigraphy including SPECT/CT [2] and 18F-DOPA PET/CT [3] in the detection of gastroenteropancreatic neuroendocrine tumours (GEP NETs). NETs, however, have a wide range of cellular differentiation. 18F-FDG PET/CT is of limited value in well-differentiated NETs but of high value in poorly differentiated NETs. Somatostatin receptor PET/CT shows contrary results [4]. As both 18F-FDG PET/CT and somatostatin receptor PET/CT exploit distinct tumour characteristics they are complementary for tumour staging. Small insulinomas are difficult to detect with 18F-FDG PET/CT, somatostatin receptor PET/CT, 18F-DOPA PET/CT and morphological imaging. Targeting of Glucagon-like peptide-1 receptors using radiolabelled exendin-4 has shown to be highly effective in the detection of these tumours [5]. Clinical studies have shown higher tumour uptake of radiolabelled somatostatin receptor antagonists than somatostatin receptor agonists [6]. As a result radiolabelled somatostatin receptor antagonists may have a significant impact on imaging of NETs.

A multianalyte algorithm PCR-based gene blood test compared to single analyte ELISA-based blood tests for neuroendocrine tumor detection.

e15168 Background: A critical requirement in NET management is a blood biomarker test that is sensitive, specific and reproducible. We evaluated a PCR-based 51 transcript signature, the NETest, to detect tumors, compared it to Chromogranin A (CgA), pancreastatin and neurokinin A. Methods: The multigene signature was evaluated in prospectively collected NETs (n=41, 61% small intestinal, 50% had metastastic disease, 44% under treatment). These were age (NETs: mean 56.9, range: 31-76; controls: mean 56.4, range: 33-75) and sex-matched (M:F = 10:31) with controls (1:1). All samples were analyzed by a 2-step PCR (51 marker genes) protocol and ELISAs: (DAKO-CgA), pancreastatin (MyBiosource-PST) and neurokinin A (RayBiotech-NKA). Sensitivity comparisons included chi-square, non-parametric measurements, ROC curves and predictive feature importance analyses. Results: PCR analysis was robust (inter/intra-assay variation <2%; inter/intra-assay reproducibility: <1.2). NETest performance metrics were: sensitivity 92.8%, specificity 92.8%, PPV 92.8% and NPV 92.8%. For the single analyte ELISA assays, metrics ranged from sensitivities: 75.6-80.5%, specificities: 31.7-87.8%, PPVs: 54.1-86.1% and NPVs: 61.9-78.3%. The AUCs from ROC analysis were: NETest: 0.96±0.025, CgA: 0.67±0.06, pancreastatin: 0.51±0.07 and neurokinin A: 0.73±0.05. The multigene transcript NETest was significantly better than any single analyte test (difference between areas: 0.13-0.45, Z-statistic = 2.6-6.58, p<0.01). Predictive Feature Importance analysis determined that NETest contributed the most value (61%) in arriving at the correct diagnosis compared to NKA (21%), CgA (9%), and PST (8%). Conclusions: A 51 panel multigene blood transcript analysis is significantly more sensitive than any single analyte assay (CgA, PST or NKA) for NET detection. The test is robust (<2% variation) and efficient (>93%). Our data indicate that a blood-based multigene analytic measurement will provide data that enables early detection of disease recurrence and predicts the efficacy of therapy.

Detection of neuroendocrine tumours in the small intestines using contrast-enhanced multiphase Ga-68 DOTATOC PET/CT: the potential role of arterial hyperperfusion.

BackgroundInterpretation of small intestinal neuroendocrine tumours (NETs) by Ga-68 DOTATOC PET/CT can be difficult. The potential benefit of arterial hyperperfusion for the detection of NETs was evaluated.MethodsBetween 2006 and 2009, 320 consecutive Ga-68 DOTATOC PET/CT examinations, performed for NETs, revealed 40 lesions suggesting intestinal NETs in 25 patients. Two groups of lesions were distinguished: epigastric lesions evaluable in the arterial and venous CT scan (Group 1) and hypogastrial lesions evaluable in the venous CT scan only (Group 2). Lesions were jointly rated by two radiologists and a nuclear medicine physician. Maximum standard uptake values (SUVmax) of lesions and background were assessed. The reference standard was histology (available for 28 lesions) or follow-up (for a mean of 22.9 months).ResultsPET detected all suspicious lesions but was false positive in 3 lesions. In Group 1 the arterial scan performed significantly better than the venous scan (p = 0.008). Diagnostic performance was better in Group 1 than in Group 2 (p < 0.001). SUVmax of true positive lesions were significantly higher than background SUVmax (p < 0.001) and SUVmax of false positive lesions (p = 0.005).ConclusionsThe arterial phase of multiphase Ga-68 DOTATOC PET/CT might improve the localization of intestinal NETs and, thereby, improve the overall diagnostic accuracy of this modality in the assessment of intestinal NETs by adding information about lesion perfusion not available when only venous CT is performed.

Synthesis and radiolabeling of 111In-core-cross linked polymeric micelle-octreotide for near-infrared fluoroscopy and single photon emission computed tomography imaging

The objective of this study was the development of a dual-modality imaging device, namely 111In-core-cross-linked polymeric micelle (CCPM)-octreotide, for neuroendocrine tumor detection, using near-infrared fluoroscopy (NIRF) and single photon emission computed tomography (SPECT). The tumor targeting ability of the 111In-labeled CCPM-octreotide was evaluated in a tumor mouse model. SPECT/CT, NIRF and gamma imaging results showed high tumor uptake of 111In-labeled CCPM-octreotide. In contrast, there was a much lower signal in the same mouse model injected with 111In-labeled CCPM. The high accumulation of 111In-labeled CCPM-octreotide in U87 tumor was reduced after co-injection with an excess amount of CCPM-octreotide. These results suggested CCPM-octreotide’s potential applications in tumor diagnosis, drug delivery and molecular imaging.

The Diagnostic Efficiency of 99mTc-EDDA/HYNIC-Octreotate SPECT-CT in Comparison with 111In-Pentetrotide in the Detection of Neuroendocrine Tumours

Objective: The aim of this study was to assess the diagnostic efficiency of 99mTc-EDDA/HYNIC-Octreotate in comparison with 111Inpentetrotide scintigraphy in the detection of neuroendocrine tumors. This study also evaluates the impact of SPECT-CT hybrid imaging on somatostatin receptor scintigraphy (SRS) interpretation and clinical management of these tumors. Methods: Fourteen patients were included in the study. All patients underwent a whole body and SPECT-CT imaging with both 99mTc- EDDA/HYNIC-octreotate and 111In-pentetrotide. Images were evaluated both visually and semiquantitatively. Results: On patient basis, the diagnostic results of both studies were similar. The number of lesions detected by 99mTc- EDDA/HYNICOctreotate were higher than the number of lesions detected by 111In-pentetrotide however the difference was not significant (40/43( 93%), 36/43 (83%) p=0.109). Semiquantitative analysis showed higher tumor/organ count ratios for both whole-body and SPECT 99mTc- EDDA/HYNIC-Octreotate scans. Conclusion: The results of this study suggested that, 99mTc- EDDA/HYNIC-Octreotate may be a better alternative to 111In- pentetrotide due to high image quality and lower radiation dose. SPECT/CT is a valuable tool for the assessment of neuroendocrine tumors by providing the precise anatomic localization of scintigraphic findings thus improving lesion detectability and characterization.Conflict of interest:None declared.

Comparison of abdominal MRI with diffusion-weighted imaging to 68Ga-DOTATATE PET/CT in detection of neuroendocrine tumors of the pancreas

The aim of the study was to evaluate contrast-enhanced MRI, diffusion-weighted MRI (DW MRI), and (68)Ga-DOTATATE positron emission tomography (PET)/CT in the detection of intermediate to well-differentiated neuroendocrine tumors (NET) of the pancreas. Eighteen patients with pathologically proven pancreatic NET who underwent MRI including DW MRI and PET/CT within 6 weeks of each other were included in this retrospective study. Two radiologists evaluated T2-weighted (T2w), T2w + DW MRI, T2w + contrast-enhanced T1-weighted (CE T1w) MR images, and PET/CT for NET detection. The sensitivity and level of diagnostic confidence were compared among modalities using McNemar's test and a Wilcoxon signed rank test. Apparent diffusion coefficients (ADC) of pancreatic NETs and normal pancreatic tissue were compared with Student's t test. Of the NETs, 8/23 (34.8 %) and 9/23 (39.1 %) were detected on T2w images by observers 1 and 2, respectively. Detection rates improved significantly by combining T2w images with DW MRI (observer 1: 14/23 = 61 %; observer 2: 15/23 = 65.2 %; p < 0.05) or CE T1w images (observer 1: 14/23 = 61 %; observer 2: 15/23 = 65.2 %; p < 0.05). Detection rates of pancreatic NET with PET/CT (both observers: 23/23 = 100 %) were statistically significantly higher than with MRI (p < 0.05). The mean ADC value of NET (1.02 ± 0.26 × 10(-3) mm(2)/s) was statistically significantly lower than that of normal pancreatic tissue (1.48 ± 0.39 × 10(-3) mm(2)/s). DW MRI is a valuable adjunct to T2w imaging and comparable to CE T1w imaging in pancreatic NET detection, quantitatively differentiating between NET and normal pancreatic tissue with ADC measurements. (68)Ga-DOTATATE PET/CT is more sensitive than MRI in the detection of pancreatic NET.

Terminal Ileum Neuroendocrine Incidentaloma in a Patient With Sporadic Medullary Thyroid Carcinoma

An incidentaloma is a mass lesion incidentally found, of uncertain significance, and clinically inert. Although incidentaloma is commonly referred to designate an adrenal lesion, it can denote any incidental lesion of other organs. We describe the unexpected finding of an ileum neuroendocrine incidentaloma detected by 6-L-(18F)-fluorodihydroxyphenylalanine (FDOPA) PET/CT performed in an asymptomatic patient with history of sporadic medullary thyroid carcinoma and biochemical suspicion of recurrent disease. This report underlines the high FDOPA PET/CT sensitivity for neuroendocrine tumor detection and the need of complementary diagnostic investigations elucidating the significance of extraphysiological FDOPA intestinal uptake, even in patients with unrelated primary cancer.

68Ga DOTANOC PET/CT Detects Medullary Thyroid Cancer Relapse at Bone Level

A patient with a history of radical thyroidectomy for medullary thyroid carcinoma (MTC) was studied by 68Ga [DOTA,1-Nal3]octreotide PET/CT for suspected relapse. PET/CT documented a focal area of somatostatin receptors expression at bone level. Although 68Ga DOTA-peptides PET has been successfully used for the detection of neuroendocrine tumors, its role in MTC patients is still under evaluation. In fact, although deriving from the neural crest, MTC cells may show a variable expression of somatostatin receptors. This case shows that PET/CT with DOTANOC may be a useful complementary imaging modality in patients with well-differentiated MTC.

Comparison of neuroendocrine tumor detection and characterization using DOTATOC-PET in correlation with contrast enhanced CT and delayed contrast enhanced MRI

PurposeWe evaluated the rate of successful characterization of gastroenteropancreatic neuroendocrine tumors (NETs) present with an increased somatostatin receptor, comparing CE-CT with CE-MRI, each in correlation with DOTATOC-PET. Methods and materials8 patients with GEP-NET were imaged using CE-MRI (Gd-EOB-DTPA), CE-CT (Imeron 400) and DOTATOC-PET. Contrast-enhancement of normal liver-tissue and metastasis was quantified with ROI-technique. Tumor delineation was assessed with visual-score in blind-read-analysis by two experienced radiologists. ResultsOut of 40 liver metastases in patients with NETs, all were detected by CE-MRI and the lesion extent could be adequately assessed, whereas CT failed to detect 20% of all metastases. The blind-read-score of CT in arterial and portal phase was median −0.65 and −1.4, respectively, and 2.7 for delayed-MRI. The quantitative ROI-analysis presented an improved contrast-enhancement-ratio with a median of 1.2, 1.6 and 3.3 for CE-CT arterial, portal-phase and delayed-MRI respectively. ConclusionLate CE-MRI was superior to CE-CT in providing additionally morphologic characterization and exact lesion extension of hepatic metastases from neuroendocrine tumor detected with DOTATOC-PET. Therefore, late enhanced Gd-EOB-DTPA-MRI seems to be the adequate imaging modality for combination with DOTATOC-PET to provide complementary (macroscopic and molecular) tumor characterization in hepatic metastasized NETs.

The diagnostic role of 68Ga-DOTATATE PET/CT in the detection of neuroendocrine tumours

Positron emission tomography (PET) combined with computer tomography (CT) using (68)Ga-DOTATATE is a promising method for the evaluation of patients with recognised or suspected neuroendocrine tumours (NET). The aim of this study was to assess the diagnostic value of (68)Ga-DOTATATE PET/CT in the visualisation of the expression of somatostatin receptors (SSTR) and identification of new lesions. Between December 2009 and January 2011 ninety-seven patients with confirmed (88 cases) or suspected (9 cases) NET underwent (68)Ga DOTATATE PET/CT. The primary, confirmed or suspected, NET localizations were: GEP tumours--71 patients; medullary thyroid carcinoma--4 patients; cancer of an unknown primary--14 patients; and NET in other localisations--8 patients. PET/CT acquisitions were performed using standard techniques, 45 to 60 minutes after the intravenous injection of 111-185 MBq (68)Ga-DOTATATE. (68)Ga-DOTATATE PET/CT detected the presence of lesions demonstrating the somatostatin receptor affinity in 50 of the 97 patients (51.5%) and was negative in 47 patients (48.5%). Among 14 patients with metastatic unknown primary cancer, in 5 patients (45.5%) the primary tumour site was identified, and in 4 patients with medullary thyroid cancer distant metastases with SSTR expression were localized in only one patient. Our findings confirm the diagnostic role of (68)Ga-DOTATATE PET/CT as an accurate method of identifying primary tumours and distant metastases. It provides information on tumour cell receptors status, which has a significant bearing on planning target radionuclide therapy. Overall, (68)Ga-DOTATATE PET/CT can be used in staging, re-staging, and in regular follow up of oncology patients.

Addition of Octreotide Functional Imaging to Cross-Sectional Computed Tomography or Magnetic Resonance Imaging for the Detection of Neuroendocrine Tumors: Added Value or an Anachronism?

Addition of Octreotide Functional Imaging to Cross-Sectional Computed Tomography or Magnetic Resonance Imaging for the Detection of Neuroendocrine Tumors: Added Value or an Anachronism?

68Ga-DOTA-NOC PET/CT Imaging of Neuroendocrine Tumors: Comparison with 111In-DTPA-Octreotide (OctreoScan®)

Recent data have indicated that ⁶⁸Ga-DOTA-NOC positron emission tomography/X-ray computed tomography (PET/CT) may yield improved images in a shorter acquisition protocol than ¹¹¹In-DTPA-octreotide (OctreoScan®, OCT). Therefore, we performed a prospective comparison of ⁶⁸Ga-DOTA-NOC and OCT for the detection of neuroendocrine tumors (NETs). Nineteen patients (eight carcinoid, nine pancreatic NETs, and two NE carcinoma of unknown origin) with previous positive OCT scans underwent ⁶⁸Ga-DOTA-NOC PET/CT and OCT single-photon emission computed tomography imaging for staging or follow-up. Findings were compared by region and verified with conventional imaging. All images of both modalities demonstrated focal uptake, often at multiple sites. ⁶⁸Ga-DOTA-NOC images were clearer than OCT images, facilitating interpretation. Similar foci were identified with both modalities in 41 regions, with additional foci on ⁶⁸Ga-DOTA-NOC in 21 and on OCT in 15 regions. CT, magnetic resonance imaging, or ultrasound confirmed the concordant findings in 31 of 41 regions and findings seen with ⁶⁸Ga-DOTA-NOC only in 15 of 21 regions. Findings seen with OCT only were less clear and were only confirmed in 4 of 15 regions. ⁶⁸Ga-DOTA-NOC had impact on staging in four patients and on management in three patients. Although ⁶⁸Ga-DOTA-NOC and OCT images were similar, in this study, ⁶⁸Ga-DOTA-NOC demonstrated more true positive tumor foci and was better tolerated by patients. This direct comparison supports replacement of OCT with ⁶⁸Ga-DOTA-NOC-PET/CT in the evaluation of NETs.

Molekulare Bildgebung neuroendokriner Tumoren mit68Ga-markierten Peptiden (Somatostatinrezeptor-PET/CT)

Die Rezeptor-PET/CT mit 68Ga-markierten Somatostatinanaloga (DOTA-NOC, DOTA-TOC oder DOTA-TATE) ermöglicht die hochsensitive molekulare Bildgebung neuroendokriner Tumoren (NET) aufgrund der Expression von Somatostatinrezeptoren und die Erfassung verschiedener Rezeptorsubtypen. Unsere Ergebnisse bei über 3 000 Untersuchungen zeigen, dass die Rezeptor-PET/CT eine erheblich höhere Nachweisgenauigkeit hat, als die konventionelle Szintigrafie (auch wenn diese in SPECT/CT-Technik erfolgt), und dass eine sehr exakte topografische Zuordnung der Tumorherde möglich ist. Mit der Berechnung von Standardized Uptake Values (SUV) stehen reproduzierbare und untersucherunabhängige Messwerte zur Verfügung, die es ermöglichen, Patienten für die Radiorezeptortherapie zu selektionieren und den Therapieverlauf zu überwachen. Die Rezeptor-PET/CT ist das sensitivstes Verfahren zum Nachweis von unbekannten Primärtumoren (CUP-Syndrom), was insbesondere für die Detektion von Pankreas- und Dünndarm-NET gilt; sie ermöglicht eine Ganzkörperuntersuchung („one stop shop”) zum Staging sowie die Selektion von Patienten zur Radiorezeptortherapie und die Tumornachsorge mit einem patientenfreundlichen Verfahren, das schnell (innerhalb einer Stunde) durchführbar ist und mit geringerer Strahlenexposition als die einer konventionellen Ganzkörper-CT erfolgen kann. Die Verwendung des 68Ge/68Ga-Generators hat sich unter klinischen Bedingungen über mehrere Jahre zuverlässig bewährt. Der effektive Kostenaufwand für 68Ga-markierte Somatostatinanaloga dürfte bei entsprechenden Untersuchungszahlen geringer sein, als der für die bisherige szintigrafische Diagnostik. Die Entwicklung anderer tumorspezifischer Peptide sowie weiterer DOTA- oder NOTA-gekoppelter Radiopharmazeutika eröffnet für die Zukunft neue Perspektiven, die letztendlich dazu führen könnten, dass der 68Ga-Generator für die PET/CT künftig eine ähnlich bedeutende Rolle spielen wird, wie dies für den 99mTc-Generator und die konventionelle Gammakamera seit Jahrzenten der Fall ist.

68Ga-DOTA-NOC: a new PET tracer for evaluating patients with bronchial carcinoid

Conventional imaging techniques [computed tomography (CT), ultrasound, magnetic resonance] and somatostatin receptor scintigraphy are often insufficient to make a conclusive diagnosis of bronchial carcinoid (BC). PET is commonly used for the assessment of lung cancer but 18F-fluorodeoxyglucose, the most frequently used PET tracer, presents a low sensitivity for the detection of neuroendocrine tumours (NETs). New PET radiopharmaceuticals such as 68Ga-DOTA peptides, which directly bind to somatostatin receptors and are usually expressed on NET cell surfaces, have been reported to be superior to both morphological and somatostatin receptor scintigraphy imaging for gastroenteropancreatic NETs. However, their role in BC has never been evaluated. Our aim is to evaluate the role of 68Ga-DOTA-NOC (68Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-octreotide) PET for the assessment of BC patients. Ten patients with pathologically proven well-differentiated BC and one patient with highly suggestive CT images for BC were studied by 68Ga-DOTA-NOC PET/CT. PET findings were compared with clinical follow-up, pathology and contrast-enhanced CT findings. 68Ga-DOTA-NOC PET/CT detected at least one lesion in nine of 11 patients and was negative in two. PET/CT and contrast-enhanced CT were discordant in eight of 11 patients, whereas in only three patients both provided similar results. PET/CT detected a higher number of lesions in five patients and excluded malignancy at sites considered positive on CT in three of 11; follow-up confirmed PET/CT findings in all patients. In PET/CT-positive patients, the mean maximal standardized uptake value was 25.9 [4.4-60.5]. On a clinical basis, PET/CT provided additional information in nine of 11 patients leading to the changes in the clinical management of three of nine patients. PET/CT with Ga-DOTA-NOC was useful in BC patients because it led to a better evaluation of the extent of the disease.

Computertomographie bei Pankreastumoren

Computed tomography (CT) and in particular multi-detector row computed tomography (MDCT), also known as multislice CT (MSCT), is ideally suited for detecting pancreatic tumors because of the high spatial resolution.The method of choice is hydro-CT which involves distension of the stomach and duodenum by administration of 1-1.5 l water as a negative contrast medium under medically induced hypotension by administration of buscopan. The patient is laid on the right side at an angle of 30-45 degrees in order to obtain an artefact-free image of the close anatomical relationship around the pancreas head. In addition, curved MPRs or in rare cases 3D reconstructions could be very helpful in identifying the critical anatomic tumor site in the neighbourhood of the visceral vessel system. After the correct diagnosis of an adenocarcinoma has been made only 20% of all patients are shown to have a surgically resectable disease, but the overall survival rate is significantly higher after resection in combination with a multimodal tumor therapy strategy. The reason is that the correct diagnosis of the resectability of the tumor is one of the main criteria for overall survival of these patients. Currently practically all pancreatic tumors can be detected using MDCT and the detection rate varies between 70% and 100% (most recent literature references give a sensitivity of 89% and specificity up to 99%). In some rare cases the differentiation between focal necrotizing pancreatitis and pancreatic carcinoma can be difficult even with sophisticated protocols. Resectability can be correctly diagnosed with MDCT with a sensitivity of 94% and a specificity of 89%. MDCT is an ideal tool for the detection of neuroendocrine tumors, metastases and for the differentiation of cystic pancreatic lesions such as pseudocysts, microcystic adenomas or intraductal papillary mucinous neoplasms (IPMN). Particularly, the differentiation of the latter into benign, borderline or malignant transformation is not always possible, but indirect signs, such as small nodules adjacent to the ductal wall, the diameter of the pancreatic duct, or a direct communication between cystic lesions and duct can be detected because of the high spatial resolution and is comparable to the findings in MRI. Moreover MD-CT is an ideal procedure for the differentiation of local tumor stages in patients under neoadjuvant or adjuvant chemotherapy.

Detection of Neuroendocrine Tumors of the Small Bowel by Double Balloon Enteroscopy

Neuroendocrine tumors (NET) account for one-third of all small bowel neoplasms. The search for the primary tumor in NET is important, even though it is difficult to localize, as its surgical excision leads to a better prognosis, even in metastasized stages of the disease. The objective of this study was to evaluate the use of double balloon enteroscopy (DBE) for the detection of the primary tumor in patients with NET. Twelve consecutive patients (eight women, four men) with suspected carcinoid syndrome, either metastatic to the liver (n=5), symptoms of a neuroendocrine tumor with elevated tumor markers (n=5), or obscure gastrointestinal bleeding (n=2) underwent DBE for the search of the primary tumor or the source of bleeding. All patients underwent abdominal sonography and a computed tomography (CT) scan, esophagogastroduodenoscopy (EGD), ileocolonoscopy, and octreotide scintigraphy prior to DBE. Capsule endoscopy was performed in four patients. A total of 17 DBE were performed in the 12 patients. The CT scan and sonography of the abdomen as well as EGD and ileocolonoscopy were unable to detect the primary tumor in any patient. A submucosal tumor of the ileum or the jejunum could be detected by DBE was detected in seven patients (58%) (anal route, n=4; oral route, n=3). In four of these patients (33%) this finding could be confirmed by the surgical resection of a NET. In two patients (17%) with a submucosal ileum protrusion suspicious for NET, laparotomy and intraoperative endoscopy did not confirm the tumor. In this study, the diagnostic yield of DBE for primary tumor search in patients with metastatic or suspected NET was 33%. Although endoscopic small bowel investigation by DBE seems to enrich the diagnostic possibilities for the diagnosis of small bowel-NET, at the present time DBE should only be performed in selected cases, possibly based on a positive previous work-up.

Somatostatin receptor scintigraphy in thoracic diseases

Somatostatin (SS) receptor scintigraphy is useful for the diagnosis of lesions with high density of SS receptors, and above all neuroendocrine tumors. For several years, only indium-labeled octreotide has been applied to visualise in vivo tissues with SS receptor overexpression. Radiolabeled octreotide became the gold standard for the detection of neuroendocrine tumors. More recently, however, several new SS analogues with varying affinity for SS receptor subtypes have been developed, and different radionuclides as radiolabels have been introduced. Moreover, significant improvements have been made by the introduction of hybrid machines, such as single photon emission computed tomography/ computed tomography (SPECT/CT) or positron emission tomography (PET)/CT that enable to perform whole-body imaging quickly and with high anatomical resolution in several body areas, including the chest. The development of more specific radiopharmaceuticals, together with the modern technique of imaging, may provide excellent quality images with high contrast, allowing to depict very small lesions and making them easy to interpret. Indeed, in the management of SS receptor-positive lesions, the contribution of nuclear medicine is essential in several clinical settings, such as initial diagnosis, disease staging, follow-up, treatment planning, and treatment monitoring. In addition, the tracer uptake might be used as a prognostic parameter and as a predictor of treatment response. In the chest, apart in (neuro)endocrine tumors, SS receptors have been demonstrated in granulomatous diseases, like sarcoidosis and other immune-mediated disorders, such as anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. In this paper we review and discuss the role of SS receptor scintigraphy in diagnosis, staging or follow- up of thoracic SS receptor-positive lesions.