Nuclear medicine in the detection and management of pancreatic islet-cell tumours

Over the last decade somatostatin receptor scintigraphy using various derivatives of long-acting somatostatin analogues has gained its place in the management of pancreatic islet-cell tumours. Scintigraphy is based on the high-affinity binding of such somatostatin analogues to receptors over-expressed by these tumour types. Following the introduction of (111)In-DTPA-D-Phe(1)-octreotide, clinical studies with radiolabelled DOTA-Tyr(3)-octreotide and DOTA-Tyr(3)-octreotate derivatives have shown considerable improvement of imaging results with increased tumour uptake. One of the newer developments, (68)Ga-labelled DOTA-Tyr(3)-octreotide, has shown promising results in patients with pancreatic islet-cell tumours, based on the high-affinity binding to the somatostatin receptor subtype 2 in combination with positron emission tomography (PET) technology. Other peptides--such as ligands for the gastrin/CCK2 receptors or vasoactive intestinal peptide (VIP)--have also been studied for imaging pancreatic cell tumours. Whereas small-sized gastrinoma, somatostatinoma, glucagonoma, carcinoid and VIPoma are frequently detected by somatostatin receptor scintigraphy, insulinoma may escape detection due to reduced receptor expression. Following peptide receptor scintigraphy, a change in patient management is reported in up to 30% of patients. When labelled with (90)Y or (177)Lu, some somatostatin analogues have been applied to patients in advanced stages of the disease. Despite positive response data in 50% of patients, long-term results and survival rates are lacking.     

Imaging and localization of islet-cell tumours of the pancreas on CT and MRI

Islet-cell tumours are neuroendocrine tumours that arise from the endocrine pancreas. They may be associated with a variety of syndromes and are subclassified into functioning and non-functioning tumours. They range from benign to malignant. They demonstrate characteristic features when imaged with both computed tomography (CT) and magnetic resonance imaging (MRI). Sensitivity and specificity, as well as detection of extrapancreatic extension, are generally superior with MRI. However, CT is currently still more readily available to patients. Multiphase, post-contrast series are commended for the evaluation of islet-cell tumours with either modality.     

Nuclear imaging of neuroendocrine tumours

The diagnosis of neuroendocrine tumours (NETs) and monitoring of therapy in many patients relies mainly on morphological imaging techniques such as computed tomography (CT), ultrasound (US) and magnetic resonance imaging (MRI). However, functional imaging modalities--such as somatostatin receptor scintigraphy (SRS)--have great impact on patient management by providing tools for better staging of the disease, visualization of occult tumour, and evaluation of eligibility for somatostatin analogue treatment. Positron emission tomography (PET) using (18)F-fluoro-deoxy-glucose (FDG) is a powerful functional modality for oncological imaging. Unfortunately, FDG is not accumulated in NETs except in the case of dedifferentiated tumours and tumours with high proliferative activity. Based on the concept of amine precursor uptake and decarboxylation (APUD), the (18)F- and (11)C-labelled amine precursors L-dihydroxyphenylalanine and 5-hydroxy-L-tryptophan (5-HTP) have been utilized for PET imaging of NETs. In comparative studies of patients with a variety of NETs, (11)C5-HTP-PET proved better than CT and SRS by visualizing additional small lesions. With carbidopa premedication orally before (11)C5-HTP-PET examination the tumour uptake could be increased and the urinary radioactivity concentration considerably reduced. This concept may also be applied to (18)F-L-DOPA-PET, a method which in a limited number of studies has gained additional diagnostic information in NET patients compared to SRS and morphological imaging. (68)Ga is available from an in-house generator and has been utilized for labelling of somatostatin analogues for PET imaging of NETs with promising results in a small number of patients. However, SRS is an established functional imaging method for patients with NETs, whereas the role for PET in the clinical routine needs further evaluation in comparative studies in larger groups of patients.     

PET imaging in endocrine tumours

The role of PET in the assessment of endocrine tumours has been, until recently, restricted to the use of (18)F-fluoro-deoxy-D-glucose ((18)F-FDG). Being a marker of metabolically active lesions that show high grading and low differentiation, FDG is not ideal for this purpose since the majority of endocrine tumours are slow growing and highly differentiated. It is however useful when dedifferentiation takes place and provides excellent prognostic information. A number of hormone precursors and amino acids are labelled with (11)C and used successfully in the management of parathyroid, adrenal and pituitary tumours. However, the short half-life of (11)C radiopharmaceuticals restricts their use to centres with access to an on-site cyclotron, while the high cost of production may limit their use to research purposes. A promising new positron-emission tomography (PET) tracer is Gallium-68 obtained by elution from a long shelf-life generator that makes it economic and cyclotron-independent. Its short half-life and flexible labelling ability to a wide range of peptides and antibodies makes it ideal for PET imaging. In addition to imaging GEP-NETs and phaeochromocytoma, it has the potential to be used in a wider range of endocrine tumours.     

Functional imaging of neuroendocrine tumours with PET

Several pathophysiological attributes of neuroendocrine tumours (NET) can be addressed by specific radiolabelled probes. This paper provides an overview on the different radiopharmaceuticals that have been developed for Positron Emission Tomography (PET) of neuroendocrine tumours. A review of the literature on 18F-fluordeoxyglucose (FDG), biogenic amine precursors, somatostatin analogues and hormone syntheses markers is presented. Due to the highly specific tracers that lack any clear anatomical landmarking the advantages of integrated PET/CT are obvious. Amine precursors should be employed in most gastroenteropancreatic NET, FDG should be preserved for more aggressive, less differentiated NETs. Somatostatin analogues are the most promising tracers, since they can improve dosimetry in cases in which radiopeptide therapies are planned. In conclusion, the individual diagnostic approach using PET or the integrated PET/CT should be tailored depending on the histological classification and the differentiation of the tumour.     

The optimal imaging of adrenal tumours: a comparison of different methods

Computed tomography (CT; unenhanced, followed by contrast-enhanced examinations) is the cornerstone of imaging of adrenal tumours. Attenuation values of <10 Hounsfield units on an unenhanced CT are practically diagnostic for adenomas. When lesions cannot be characterised adequately with CT, magnetic resonance imaging (MRI) evaluation (with T1- and T2-weighted sequences and chemical shift and fat-suppression refinements) is sought. Functional nuclear medicine imaging is useful for adrenal lesions that are not adequately characterised with CT and MRI. Scintigraphy with [(131)I]-6-iodomethyl norcholesterol (a labelled cholesterol analogue) can differentiate adrenal cortical adenomas from carcinomas. Phaeochromocytomas appear as areas of abnormal and/or increased uptake of [(123)I]- and [(131)I]-meta-iodobenzylguanidine (a labelled noradrenaline analogue). The specific and useful roles of adrenal imaging include the characterisation of tumours, assessment of true tumour size, differentiation of adenomas from carcinomas and metastases, and differentiation of hyperfunctioning from non-functioning lesions. Adrenal imaging complements and assists the clinical and hormonal evaluation of adrenal tumours.     

Diagnostic imaging of liver tumours. Current status

Nowadays, contrast enhanced ultrasound (CEUS) is an imaging technique equivalent to multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) for the detection and characterization of focal liver lesions. These methods have comparable sensitivity and specificity in differentiating a liver lesion as "benign" or "malignant". For benign lesions, CEUS is the recommended method of the choice. In unclear cases, or if CEUS is not available, MRI or CT are the methods of the second choice. If a benign tumor remains unclear, then a needle biopsy is recommended. In the case of a malignant tumor, it is necessary to use a second imaging technique besides CEUS. In addition to the detection and characterization of a liver tumor, CT and MRI provide information on the extrahepatic spread of a tumor, particularly into the lung or retroperitoneum. The rapid development of surgical and interventional approaches requires accurate information on the character and number of malignant liver lesions. Therefore, the combined use of CEUS and MDCT or MRI currently represents the most modern and optimal standard of imaging. The standardization of CT and MRI protocols has increased the general diagnostic level of these images. Adequate training and a certificate for the use of CEUS is recommended in order to maintain the high diagnostic level of this method (EFSUMB guide lines). An optimal interdisciplinary imaging strategy for focal liver lesions minimises unnecessary invasive or potentially harmful imaging and reduces health costs.     

Localisation of mesenchymal tumours by somatostatin receptor imaging

Oncogenic osteomalacia, an acquired hypophosphataemic syndrome associated with mesenchymal tumours, is characterised by hypophosphataemia secondary to inappropriate phosphaturia, reduced concentrations of serum calcitriol, and defective bone mineralisation. Removal of these tumours results in complete reversal of these biochemical defects. However, because these tumours are small, slow-growing, and frequently situated in unusual anatomical sites, conventional imaging techniques often fail to detect them. Since mesenchymal tumours express somatostatin receptors, we postulated that somatostatin analogues would be able to detect these tumours. We did Indium-111 labeled pentetreotide imaging in seven patients with oncogenic osteomalacia. In five patients, we identified a mesenchymal tumour, and clinical improvement occurred after tumour resection. Our findings suggest that 111In-pentetreotide imaging effectively detects occult mesenchymal tumours and facilitates surgical treatment of oncogenic osteomalacia.     

Radiological and nuclear medicine imaging of gastroenteropancreatic neuroendocrine tumours

Neuroendocrine tumours (NETs) comprise a heterogeneous group of neoplasms with very varying clinical expression. A functioning NET, for instance in the pancreas, may be very small and yet give rise to severe endocrine symptoms whereas a patient with a small bowel tumour may present with diffuse symptoms and disseminated disease with a palpable bulky liver. Imaging of NETs is therefore challenging and the imaging needs in the various patients are diverse. The basic modalities for NET imaging are computed tomography (CT) or magnetic resonance imaging (MRI) in combination with somatostatin receptor imaging (SMI) by scintigraphy with 111In-labelled octreotide (OctreoScan) or more recently by positron emission tomography (PET) with 68Ga-labelled somatostatin analogues. In this review these various morphological and functional imaging modalities and important methodological aspects are described. Imaging requirements for the various types of NETs are discussed and typical image findings are illustrated.     

Diarrhea associated with pancreatic islet-cell tumors

Summary 1. Two cases of noninsulin-secreting pancreatic islet-cell tumors presenting as severe diarrhea are reported. The first patient had steatorrhea and marked gastric hypersecretion, but no ulcer. Removal of the tumor was followed by normalization of gastric secretion and disappearance of steatorrhea. The second patient had profuse, watery diarrhea with severe fluid and electrolyte depletion. He was achlorhydric. Resection of the tumor completely relieved the diarrhea, but the patient later succumbed to pancreatic necrosis.2. On the basis of this personal experience and of a review of 45 cases described in the literature, it appears (1) that pancreatic islet-cell tumors are often responsible for diarrhea; (2) that this effect is mediated via gastric hypersecretion in a majority of instances; and (3) that stimulation of intestinal secretions is a probable mechanism in the few patients with low gastric secretion or anacidity.     

Echo-enhanced ultrasound with pulse inversion imaging： A new imaging modality for the differentiation of cystic pancreatic tumours

AIM: To describe and discuss echo-enhanced sonography in the differential diagnosis of cystic pancreatic lesions. METHODS: The pulse inversion technique (with intravenous injection of 2.4 mL SonoVue(?)) or the power-Doppler mode under the conditions of the 2nd harmonic imaging (with intravenous injection of 4 g Levovist(?)) was used for echo-enhanced sonography. RESULTS: Cystadenomas frequently showed many vessels along fibrotic strands. On the other hand, cystadenocarcinomas were poorly and chaotically vascularized. "Young pseudocysts" were frequently found to have a highly vascularised wall. However, the wall of the "old pseudocysts" was poorly vascularized. Data from prospective studies demonstrated that based on these imaging criteria the sensitivities and specificities of echo-enhanced sonography in the differentiation of cystic pancreatic masses were > 90%. CONCLUSION: Cystic pancreatic masses have a different vascularization pattern at echo-enhanced sonography. These characteristics are useful for their differential diagnosis, but histology is still the gold standard.     

Effect of antithyroid autoantibodies on pancreatic islet-cell function

Summary Insulin-dependent diabetes mellitus is frequently associated with organ-specific autoimmune diseases and/or high titers of organ-specific autoantibodies. The effects of thyroid autoantibodies on islet-cell function were examined in the present study. Islet cell surface antibody (ICSAb) was detected in sera from 6 of 40 patients with autoimmune thyroid disease (AITD) who were positive for thyroid microsomal autoantibodies (TMA). Furthermore, all of the ICSAb-positive patients had high TMA titers.In vitro study using isolated rat pancreatic islets revealed that TMA positive sera significantly suppressed glucose-induced insulin release. Only one of 19 (5%) AITD patients showed complement-dependent antibody-mediated cytotoxicity and only one of 6 AITD patients (17%) was positive for antibody-dependent cellular cytotoxicity. These results suggest that TMA has an effect on an antigen of the islet cell membrane in which insulin releasing mechanism might be involved.     

Reaction patterns of islet-cell autoantibodies in Macaca nigra

Circulating islet-cell autoantibodies (ICAAs) that reacted specifically with cytoplasmic components have been found in the blood of prediabetic Macaca nigra. The three distinct reaction patterns observed involved the majority of islet cells throughout the islet; a moderate number of cells, mainly at the islet periphery and around the vasculature; and a few cells scattered throughout the islet. Pancreas sections incubated with sera containing ICAAs followed with peroxidase-conjugated antibody were then reacted with anti-insulin, antiglucagon, or antisomatostatin antisera. The pattern associated with most of the islet cells was shown to be reactive to beta cells and was termed B-ICAA; the pattern with cells at the periphery was identified as alpha cells (A-ICAA); and the scattered cells contained somatostatin (D-ICAA). None of the three islet hormones were able to block ICAA reaction after overnight incubation, so the ICAAs are not anti-islet hormone antibodies. The varied reactions with antigens of different secretory cells indicate release of a variety of immunogens from islet cells as they necrose and cause the formation of different ICAAs.     

老年颈部神经源肿瘤的MRI诊断

目的 探讨磁共振成像（MRI）对颈部神经源肿瘤的定位、定性诊断价值。方法 回顾性分析经手术及病理证实的颈部神经源肿瘤MRI31例，包括神经鞘瘤23例、神经纤维瘤7例、恶性神经源肿瘤1例。结果 依据肿瘤引起的附近间隙、血管、肌肉等移位方向进行肿瘤定位。神经鞘瘤病理上有不同组成成分，因此可根据MRI的信号特点及增强后表现对其作出定性判断。结论 MRI是诊断颈部神经源肿瘤的有效方法，最有价值的诊断指征为肿瘤的部位、肿瘤与邻近结构的关系以及肿瘤的信号变化。