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E. P. Krenning - One of the best experts on this subject based on the ideXlab platform.
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Somatostatin Receptor Scintigraphy in the Initial Staging of Low-Grade
2015Co-Authors: Pieternella J. Lugtenburg, S. W. J. Lamberts, Roelf Valkema, Hong-yoe Oei, Marinus J. Eijkemans, Wim L. Van Putten, E. P. KrenningAbstract:In this prospective study, Somatostatin Receptor (SS-R) scintig-raphy was compared with conventional staging procedures for the initial staging of patients with low-grade non-Hodgkin’s lymphoma (NHL). Methods: Fifty consecutive untreated pa-tients with low-grade NHL underwent SS-R scintigraphy as part of their initial staging. Planar images were obtained 24 and 48 h after intravenous injection of 220 MBq 111In-pentetreotide. SPECT images of the upper abdomen were obtained from all patients. SS-R scans were evaluated blindly without knowledge of the results of the conventional staging methods. SS-R scin-tigraphy findings were compared with the results of physical and radiologic examinations. Results: SS-R scintigraphy find-ings were positive in 42 of 50 patients (84%). In 10 patients (20%), the SS-R scan revealed new lesions that had not been revealed by conventional staging procedures. These 10 patients were all upgraded to a higher stage. Consequently, the treat-ment plan would have been altered in 5 patients (10%). How-ever, in 19 patients (38%), lesions apparent after conventional staging methods were missed by SS-R scintigraphy. The sensitivity of SS-R scintigraphy varied from 62 % for supradia-phragmatic lesions to 44 % for infradiaphragmatic lesions. The specificity of SS-R scintigraphy was high (98%–100%). In com-parison with CT scanning and sonography, SS-R scintigraphy is inferior for the visualization of NHL lesions in the thorax and abdomen. Conclusion: Although SS-R scintigraphy findings are positive in a large proportion of patients with low-grade NHL, in most patients only part of the lesions can be visualized. Be-cause of the limited sensitivity, we recommend SS-R scintigra-phy for initial staging of patients with low-grade NHL only in selected conditions and not for the general work-up. Key Words: Somatostatin Receptor scintigraphy; low-grade non-Hodgkin’s lymphoma; stagin
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enets consensus guidelines for the standards of care in neuroendocrine tumors Somatostatin Receptor imaging with iiiin pentetreotide
Neuroendocrinology, 2009Co-Authors: D J Kwekkeboom, E. P. Krenning, Rachida Lebtahi, Klemens Scheidhauer, Val Lewington, A Grossman, Pavel Vitek, Anders Sundin, Ursula Plockinger, Goran AkerstromAbstract:ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors : Somatostatin Receptor Imaging with In-111-Pentetreotide
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Somatostatin Receptor imaging for neuroendocrine tumors
Pituitary, 2006Co-Authors: Wouter W. De Herder, Steven W. J. Lamberts, Dik J. Kwekkeboom, Richard A. Feelders, Maarten O. Van Aken, Aart-jan Van Der Lely, E. P. KrenningAbstract:Tumors and metastases that express the Somatostatin Receptor subtypes sst_2 sst_3 or sst_5 can be visualized in vivo after injection of radiolabeled octapeptide Somatostatin analogs, like ^111In-pentetreotide. ^111In-pentetreotide scintigraphy also allows for more accurate staging of the disease by demonstrating tumor sites, which were not shown by conventional imaging. ^111In-pentetreotide scintigraphy may also detect resectable tumors that would have remained unrecognized using conventional radiological imaging techniques; it may prevent surgery with curative intent in those patients whose tumors have metastasized to a greater extend than could be detected with conventional radiological imaging and it may be used to select patients for treatment with the currently available octapeptide Somatostatin analogs or with tumor targeted radioactive treatment with radiolabelled Somatostatin analogs. ^111In-pentetreotide scintigraphy has also been used to select patients with pituitary tumors for medical treatment with octapeptide analogs, but its clinical usefulness for this purpose seems to be limited. It further allows scar tissue to be differentiated from tumor recurrence after the pituitary surgery or radiotherapy. However, a large variety of lesions in and around the pituitary region also express Somatostatin Receptors and, therefore, can be visualized by ^111In-pentetreotide scintigraphy.
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procedure guideline for Somatostatin Receptor scintigraphy with 111in pentetreotide
The Journal of Nuclear Medicine, 2001Co-Authors: Helena Balon, E. P. Krenning, Stanley J Goldsmith, Barry A Siegel, Edward B Silberstein, Otto Lang, Kevin J DonohoeAbstract:The purpose of this guideline is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of Somatostatin Receptor scintigraphy with 111In-pentetreotide. 111In-pentetreotide is a [111In-DTPA-d-Phe-] conjugate of octreotide, a Somatostatin analog
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Somatostatin Receptor mediated imaging and therapy basic science current knowledge limitations and future perspectives
European Journal of Nuclear Medicine and Molecular Imaging, 2001Co-Authors: Wouter A.p. Breeman, Willem H. Bakker, Theo J. Visser, Dik J. Kwekkeboom, Peter P. M. Kooij, Marion De Jong, Roelf Valkema, E. P. KrenningAbstract:In vivo Somatostatin Receptor-mediated scintigraphy has proven to be a valuable method for the visualisation of neuroendocrine tumours and their metastases. A new application is the use of radiolabelled analogues for Somatostatin Receptor-mediated therapy. This paper presents a review on the basic science, historical background and current knowledge of Somatostatin Receptor subtypes and their expression in neuroendocrine tumours. New Somatostatin analogues, new chelators, "new" radionuclides and combinations thereof are also discussed. Due attention is given to limitations and future perspectives of Somatostatin Receptor-mediated imaging and therapy.
Jean Claude Reubi - One of the best experts on this subject based on the ideXlab platform.
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Somatostatin Receptor subtype 2a immunohistochemistry using a new monoclonal antibody selects tumors suitable for in vivo Somatostatin Receptor targeting
The American Journal of Surgical Pathology, 2012Co-Authors: Meike Korner, Agnes Schonbrunn, Beatrice Waser, Aurel Perren, Jean Claude ReubiAbstract:High overexpression of Somatostatin Receptors in neuroendocrine tumors allows imaging and radiotherapy with radiolabeled Somatostatin analogues. To ascertain whether a tumor is suitable for in vivo Somatostatin Receptor targeting, its Somatostatin Receptor expression has to be determined. There are specific indications for use of immunohistochemistry for the Somatostatin Receptor subtype 2A, but this has up to now been limited by the lack of an adequate reliable antibody. The aim of this study was to correlate immunohistochemistry using the new monoclonal anti-Somatostatin Receptor subtype 2A antibody UMB-1 with the gold standard in vitro method quantifying Somatostatin Receptor levels in tumor tissues. A UMB-1 immunohistochemistry protocol was developed, and tumoral UMB-1 staining levels were compared with Somatostatin Receptor binding site levels quantified with in vitro I-[Tyr]-octreotide autoradiography in 89 tumors. This allowed defining an immunohistochemical staining threshold permitting to distinguish tumors with Somatostatin Receptor levels high enough for clinical applications from those with low Receptor expression. The presence of >10% positive tumor cells correctly predicted high Receptor levels in 95% of cases. In contrast, absence of UMB-1 staining truly reflected low or undetectable Somatostatin Receptor expression in 96% of tumors. If 1% to 10% of tumor cells were stained, a weak staining intensity was suggestive of low Somatostatin Receptor levels. This study allows for the first time a reliable recommendation for eligibility of an individual patient for in vivo Somatostatin Receptor targeting based on Somatostatin Receptor immunohistochemistry. Under optimal methodological conditions, UMB-1 immunohistochemistry may be equivalent to in vitro Receptor autoradiography.
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expression and localization of Somatostatin Receptor sstr1 sstr2 and sstr3 messenger rnas in primary human tumors using in situ hybridization
Cancer Research, 1994Co-Authors: Jean Claude Reubi, B Waser, Jeanclaude Schaer, G MengodAbstract:Abstract Somatostatin Receptor gene expression of SSTR1, SSTR2, and SSTR3 subtypes was evaluated by in situ hybridization in 55 human primary tumors shown to contain a high density of Somatostatin Receptors in binding assays. All 55 tumors expressed at least one SSTR subtype. Of 55 Somatostatin Receptor-positive tumors, 46 had SSTR2 mRNA; all 46 were characterized as having Receptors with a high affinity for the synthetic analogue octreotide. Of 55 tumors, 12 expressed SSTR1, and 14 expressed SSTR3 mRNA. The subtype SSTR1 was expressed alone in 4 cases, SSTR2 was expressed alone in 33 cases, and SSTR3 was expressed alone in one case. In 4 cases, all 3 SSTR were expressed simultaneously. The cases having SSTR1 mRNA were identified in binding experiments with 125I-labeled Somatostatin-14 and -28 analogues rather than with 125I-[Tyr3]-octreotide. Whereas meningiomas, neuroblastomas, pituitary adenomas, small cell lung carcinomas, lymphomas, and breast tumors expressed primarily a high abundance of SSTR2, carcinoids, islet cell carcinomas, medullary thyroid carcinomas, and ovarian tumors had a mixed distribution of the Somatostatin Receptor subtypes. This is the first demonstration of the presence of SSTR1, SSTR2, and SSTR3 in primary human tumors using in situ hybridization. Since these Somatostatin Receptor subtypes probably mediate distinct Somatostatin actions, it may be worthwhile to search for subtype-specific analogues to use for the treatment and diagnosis of these tumors.
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In vivo Somatostatin Receptor imaging in medullary thyroid carcinoma
The Journal of clinical endocrinology and metabolism, 1993Co-Authors: Dirk Jan Kwekkeboom, Jean Claude Reubi, Steven W. J. Lamberts, H. Y. Oei, Hajo A. Bruining, Andries Mulder, E. P. KrenningAbstract:Using in vivo scintigraphy with the 111In-labeled Somatostatin analog octreotide, tumor localizations were demonstrated in 11 of 17 patients (65%) with medullary thyroid carcinoma (MTC). Tumor localizations in the liver in 7 patients, and in the thyroid in 1 patient were not detected on octreotide scintigraphy, most probably because of normal uptake of labeled octreotide in these organs. Specific Somatostatin Receptors were demonstrated in vitro on all 5 investigated tumors which had also been visualized in vivo, as well as on 1 tumor that was not. Immunohistochemically, Somatostatin was present in 1 of 6 tumors that were visualized in vivo, and in neither of 2 tumors that were not. The ratio of serum calcitonin over carcino-embryonic antigen concentrations was significantly higher in patients whose MTCs were visualized during octreotide scintigraphy than in those whose tumors were not. We have formed the following conclusions: 1) In the majority of patients with metastatic MTC, tumor sites can be visualized using octreotide scintigraphy, although this technique is insensitive in detecting liver metastases or intrathyroidal tumor; 2) The visualization of MTC during in vivo Somatostatin Receptor imaging correlates with the in vitro presence of Somatostatin Receptors; 3) The immunohistochemical presence of Somatostatin in the tumor does not seem to influence the outcome of in vivo Somatostatin Receptor imaging; and 4) Higher serum calcitonin over carcino-embryonic antigen ratios in patients whose MTC is visualized during octreotide scintigraphy might imply that Somatostatin Receptors are present on more differentiated MTC.
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Somatostatin Receptor imaging of endocrine gastrointestinal tumors.
Schweizerische medizinische Wochenschrift, 1992Co-Authors: E. P. Krenning, Jean Claude Reubi, Dirk Jan Kwekkeboom, P. Martin Van Hagen, H. Y. Oei, Peter P. M. Kooij, Ambroos E.m. Reijs, S. W. J. LambertsAbstract:UNLABELLED Somatostatin Receptors are present on various tumors of neuroendocrine origin. We recently developed a technique for the in vivo visualization of Somatostatin Receptor positive tumors, which offers a powerful alternative to tumor imaging with labeled monoclonal antibodies. Instead of injecting radiolabeled antibodies against the Somatostatin Receptor, we labeled a Somatostatin analogue ([Tyr3]-octreotide) which is known to bind specifically to the Somatostatin Receptor, and injected this labeled hormone analogue in order to visualize Somatostatin Receptor positive tumors. We previously reported the successful visualization of the primary tumors or metastases of various endocrine gastrointestinal tumors after injection of the iodinated Somatostatin analogue [123I-Tyr3]-octreotide. The primary tumors or metastases of 12 out of 13 carcinoids, 3 out of 3 gastrinomas, 2 out of 4 insulinomas, and 1 out of 1 Somatostatinoma were visualized. Using 111In-coupled octreotide, we were able to visualize 19 out of 19 carcinoids, 7 out of 7 gastrinomas, 4 out of 7 insulinomas, 1 out of 1 glucagonoma, and 3 out of 3 non-functioning endocrine pancreatic tumors, but none of 18 exocrine pancreatic tumors. In a large proportion of patients with endocrine gastrointestinal tumors, previously unrecognized metastases were demonstrated. Also, the absence or presence of in vivo visualization of these tumors after the injection of radiolabeled octreotide seems to predict the ability of octreotide therapy to control symptoms caused by hormonal secretion from these tumors. IN CONCLUSION 111In-octreotide scintigraphy is a simple and sensitive technique for localizing of the primary tumor and its metastases in the majority of patients with carcinoids or endocrine pancreatic tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
Stefan Schulz - One of the best experts on this subject based on the ideXlab platform.
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Pasireotide and octreotide stimulate distinct patterns of sst2A Somatostatin Receptor phosphorylation.
Molecular endocrinology (Baltimore Md.), 2010Co-Authors: Florian Pöll, Amelie Lupp, Diana Lehmann, Susann Illing, Mihaela Ginj, Stefan Jacobs, Ralf Stumm, Stefan SchulzAbstract:Pasireotide (SOM230) is currently under clinical evaluation as a successor compound to octreotide for the treatment of acromegaly, Cushing's disease, and carcinoid tumors. Whereas octreotide acts primarily via the sst(2A) Somatostatin Receptor, pasireotide was designed to exhibit octreotide-like sst(2A) activity combined with enhanced binding to other Somatostatin Receptor subtypes. In the present study, we used phophosite-specific antibodies to examine agonist-induced phosphorylation of the rat sst(2A) Receptor. We show that Somatostatin and octreotide stimulate the complete phosphorylation of a cluster of four threonine residues within the cytoplasmic (353)TTETQRT(359) motif in a variety of cultured cell lines in vitro as well as in intact animals in vivo. This phosphorylation was mediated by G protein-coupled Receptor kinases (GRK) 2 and 3 and followed by rapid cointernalization of the Receptor and ss-arrestin into the same endocytic vesicles. In contrast, pasireotide failed to promote substantial phosphorylation and internalization of the rat sst(2A) Receptor. In the presence of octreotide or SS-14, SOM230 showed partial agonist behavior, inhibiting phosphorylation, and internalization of sst(2A). Upon overexpression of GRK2 or GRK3, pasireotide stimulated selective phosphorylation of Thr356 and Thr359 but not of Thr353 or Thr354 within the (353)TTETQRT(359) motif. Pasireotide-mediated phosphorylation led to the formation of relatively unstable beta-arrestin-sst(2A) complexes that dissociated at or near the plasma membrane. Thus, octreotide and pasireotide are equally active in inducing classical G protein-dependent signaling via the sst(2A) Somatostatin Receptor. Yet, we find that they promote strikingly different patterns of sst(2A) Receptor phosphorylation and, hence, stimulate functionally distinct pools of beta-arrestin.
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differential effects of octreotide and pasireotide on Somatostatin Receptor internalization and trafficking in vitro
The Journal of Clinical Endocrinology and Metabolism, 2009Co-Authors: Sarah Lesche, Diana Lehmann, Falko Nagel, Herbert A Schmid, Stefan SchulzAbstract:Objective: The clinically used Somatostatin analogs, octreotide and lanreotide, act primarily by binding to Somatostatin Receptor 2 (sst2). In contrast, the novel multiReceptor ligand pasireotide (SOM230) binds with high affinity to Somatostatin Receptor subtypes sst1, sst2, sst3, and sst5. SOM230 is currently under clinical evaluation for treatment of acromegaly, Cushing’s disease, and octreotide-resistant carcinoid tumors. However, the effects of SOM230 on internalization and postendosomal sorting of individual human Somatostatin Receptor subtypes have not been determined so far. Results: Here we show that SOM230 was less potent than octreotide in inducing internalization and signaling of sst2 Receptors expressed in human embryonic kidney cells. In contrast, SOM230 was more potent than octreotide in inducing internalization and signaling of sst3 and sst5 Receptors. Both SOM230 and octreotide stimulated a rapid down-regulation of sst3 but not of sst2 or sst5 Receptors. SOM230 and octreotide profoundly di...
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Novel insights in Somatostatin Receptor physiology
European Journal of Endocrinology, 2007Co-Authors: Giovanni Tulipano, Stefan SchulzAbstract:The experimental data reviewed in the present paper deal with the molecular events underlying the agonist-dependent regulation of the distinct Somatostatin Receptor subtypes and may suggest important clues about the clinical use of Somatostatin analogs with different pattern of Receptor specificity for the in vivo targeting of tumoral Somatostatin Receptors. Somatostatin Receptor subtypes are characterized by differential β-arrestin trafficking and endosomal sorting upon agonist binding due, at least in part. to the differences in their C-terminal tails. Moreover. the subcellular expression pattern of Somatostatin Receptor subtypes and their activity in response to agonist treatment are affected by intracellular complements, such as proteins involved in intracellular vesicle trafficking. Different Somatostatin analogs may induce distinct conformations of the Receptor/ligand complex, preferentially coupled to either Receptor signaling or Receptor endocytosis.
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Novel insights in Somatostatin Receptor physiology.
European journal of endocrinology, 2007Co-Authors: Giovanni Tulipano, Stefan SchulzAbstract:The experimental data reviewed in the present paper deal with the molecular events underlying the agonist-dependent regulation of the distinct Somatostatin Receptor subtypes and may suggest important clues about the clinical use of Somatostatin analogs with different pattern of Receptor specificity for the in vivo targeting of tumoral Somatostatin Receptors. Somatostatin Receptor subtypes are characterized by differential beta-arrestin trafficking and endosomal sorting upon agonist binding due, at least in part, to the differences in their C-terminal tails. Moreover, the subcellular expression pattern of Somatostatin Receptor subtypes and their activity in response to agonist treatment are affected by intracellular complements, such as proteins involved in intracellular vesicle trafficking. Different Somatostatin analogs may induce distinct conformations of the Receptor/ligand complex, preferentially coupled to either Receptor signaling or Receptor endocytosis.
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differential β arrestin trafficking and endosomal sorting of Somatostatin Receptor subtypes
Journal of Biological Chemistry, 2004Co-Authors: Giovanni Tulipano, Ralf Stumm, Volker Höllt, Manuela Pfeiffer, Hansjurgen Kreienkamp, Stefan SchulzAbstract:The physiological responses of Somatostatin are mediated by five different G protein-coupled Receptors. Although agonist-induced endocytosis of the various Somatostatin Receptor subtypes (sst(1)-sst(5)) has been studied in detail, little is known about their postendocytic trafficking. Here we show that Somatostatin Receptors profoundly differ in patterns of beta-arrestin mobilization and endosomal sorting. The beta-arrestin-dependent trafficking of the sst(2A) Somatostatin Receptor resembled that of a class B Receptor in that upon Receptor activation, beta-arrestin and the Receptor formed stable complexes and internalized together into the same endocytic vesicles. This pattern was dependent on GRK2 (G protein-coupled Receptor kinase 2)-mediated phosphorylation of a cluster of phosphate acceptor sites within the cytoplasmic tail of the sst(2A) Receptor. Unlike other class B Receptors, however, the sst(2A) Receptor was rapidly resensitized and recycled to the plasma membrane. The beta-arrestin mobilization of the sst(3) and the sst(5) Somatostatin Receptors resembled that of a class A Receptor in that upon Receptor activation, beta-arrestin and the Receptor formed relatively unstable complexes that dissociated at or near the plasma membrane. Consequently, beta-arrestin was excluded from sst(3)-containing vesicles. Unlike other class A Receptors, a large proportion of sst(3) Receptors was subject to ubiquitin-dependent lysosomal degradation and did not rapidly recycle to the plasma membrane. The sst(4) Somatostatin Receptor is unique in that it did not exhibit agonist-dependent Receptor phosphorylation and beta-arrestin recruitment. Together, these findings may provide important clues about the regulation of Receptor responsiveness during long-term administration of Somatostatin analogs.
F Gibril - One of the best experts on this subject based on the ideXlab platform.
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Diagnostic uses of radiolabelled Somatostatin Receptor analogues in gastroenteropancreatic endocrine tumours.
Digestive and Liver Disease, 2004Co-Authors: F Gibril, Robert T. JensenAbstract:Numerous studies have established that gastroenteropancreatic endocrine tumours (carcinoids and pancreatic endocrine tumours) resemble a number of other tumours in overexpressing Somatostatin Receptors that can bind octreotide or lanreotide with high affinity (i.e. possess sst2/sst5 Receptors). Recent studies report that radiolabelled Somatostatin analogues can be used to image these tumours (Somatostatin Receptor scintigraphy) and may be useful for peptide-directed radionuclide therapy. In this paper the evidence is reviewed that has led to establishing Somatostatin Receptor scintigraphy as the initial imaging modality of choice in patients with gastroenteropancreatic tumours. This conclusion is based on an understanding of the results with conventional imaging modalities (ultrasound, computed tomographic scan, magnetic resonance imaging, angiography) available prior to Somatostatin Receptor scintigraphy and the results of studies demonstrating the sensitivity and specificity of Somatostatin Receptor scintigraphy. Most important in this regard are the results of studies that have assessed the use of Somatostatin Receptor scintigraphy on clinical management. Each of these areas is reviewed in this paper.
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Somatostatin Receptor scintigraphy in gastrinomas.
Italian journal of gastroenterology and hepatology, 1999Co-Authors: R T Jensen, F GibrilAbstract:Recent studies report that the radiolabelled synthetic Somatostatin analogue, [111In-DTPA-DPhe1]octreotide, is useful for imaging carcinoid tumours and pancreatic endocrine tumours. At present, it is unclear whether this method is superior to conventional imaging studies (computed tomography, magnetic resonance imaging, ultrasound, angiography) and what its role should be, if any, in the management of these patients. The aim of this paper is to review five recent studies performed at the National Institutes of Health in patients with Zollinger-Ellison syndrome to define the role of Somatostatin Receptor scintigraphy. Patients were from a tertiary referral centre, all had Zollinger-Ellison syndrome. In Study n. 1: the sensitivity of Somatostatin Receptor scintigraphy was assessed compared to conventional studies in 80 patients. Study n. 2: the effect of Somatostatin Receptor scintigraphy on management was determined in 122 patients. Study n. 3: ability of Somatostatin Receptor scintigraphy and other conventional methods to distinguish small hepatic metastases (< 2 cm) from hepatic haemangiomas was assessed in 29 patients. Study n. 4: Somatostatin Receptor scintigraphy, magnetic resonance imaging and bone scanning were compared in 115 consecutive patients to detect bone metastases. Study n. 5: ability of Somatostatin Receptor scintigraphy to detect gastrinomas found at surgery in 35 patients and its effect on cure rate and determinants of detection of gastrinomas by Somatostatin Receptor scintigraphy were analysed. Briefly, results showed: Study n. 1: Somatostatin Receptor scintigraphy is the most sensitive modality for detection of primary or metastatic gastrinomas; Study n. 2: Somatostatin Receptor scintigraphy changes management in 47% of cases; Study n. 3: Somatostatin Receptor scintigraphy is the only method to distinguish small liver metastases from small haemangiomas; Study n. 4: Somatostatin Receptor scintigraphy and magnetic resonance imaging have higher sensitivity and predictive values for bone metastases than bone scanning; Study n. 5: Somatostatin Receptor scintigraphy misses 33% of gastrinomas found at surgery, primarily small duodenal tumours. Size is the important factor. The use of Somatostatin Receptor scintigraphy does not increase cure rate. In conclusion, Somatostatin Receptor scintigraphy is now the imaging method of choice in patients with Zollinger-Ellison syndrome for preoperative primary tumour localization, detection of bone or liver metastases, and to distinguish small liver metastases from small hepatic haemangiomas. Its specificity appears to be high but has been poorly studied as has the use of it in combination with endoscopic ultrasound. Studies by others suggest these recommendations will apply to carcinoid tumours and other pancreatic endocrine tumours except insulinomas.
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prospective study of Somatostatin Receptor scintigraphy and its effect on operative outcome in patients with zollinger ellison syndrome
Annals of Surgery, 1998Co-Authors: H R Alexander, Douglas L Fraker, Jeffrey A Norton, David L Bartlett, Lok T Tio, Stanley B Benjamin, John L Doppman, Stephan U Goebel, Jose Serrano, F GibrilAbstract:ObjectiveTo determine the relative abilities of Somatostatin Receptor scintigraphy (SRS) and conventional imaging studies (computed tomography, magnetic resonance imaging, ultrasound, angiography) to localize gastrinomas before surgery in patients with Zollinger-Ellison syndrome (ZES) subsequentl
Carlo Capella - One of the best experts on this subject based on the ideXlab platform.
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Somatostatin Receptor type 2a immunohistochemistry in neuroendocrine tumors a proposal of scoring system correlated with Somatostatin Receptor scintigraphy
Modern Pathology, 2007Co-Authors: Marco Volante, Maria Pia Brizzi, Antongiulio Faggiano, Stefano La Rosa, Ida Rapa, Anna Maria Ferrero, Gelsomina Mansueto, Luisella Righi, Silvana Garancini, Carlo CapellaAbstract:Typing Somatostatin Receptor expression in neuroendocrine tumors is of relevance to target Somatostatin analogue-based diagnostic approach and treatment. The expanding use of immunohistochemistry to detect Somatostatin Receptors is to date not paralleled by an accurate methodological setting and standardized interpretation of the results. A multicentric study was designed to compare Somatostatin Receptor immunohistochemical expression with in vivo scintigraphic data and verify its usefulness in the clinical management of neuroendocrine tumors. After methodological setting by testing different Somatostatin Receptor antibodies, 107 cases of neuroendocrine tumors with available Somatostatin Receptor scintigraphy data and pathological material were retrospectively analyzed for Somatostatin Receptor types 2A, 3 and 5 immunohistochemical expression, and compared with scintigraphic images and, whenever available, with the clinical response to Somatostatin analogue treatment. Restricting ‘positive cases’ to the presence of a membrane pattern of staining, an overall Somatostatin Receptor type 2A immunohistochemistry/Somatostatin Receptor scintigraphy agreement of 77% (χ2 test P<0.0001) was reached. Lower concordance ratios were detected in preoperative and metastatic tumor samples, possibly as a consequence of Somatostatin Receptor expression heterogeneity. Pure Somatostatin Receptor type 2A cytoplasmic staining showed poor correlation with Somatostatin Receptor scintigraphy (54% concordance rate). The immunohistochemical detection of Somatostatin Receptor types 3 and 5, which showed almost exclusively a cytoplasmic pattern, did not improve the concordance with scintigraphic data. In a pilot series, Somatostatin Receptor type 2A immunohistochemistry correlated with clinical response in 75% of cases. In conclusion, we propose a scoring system for Somatostatin Receptor type 2A immunohistochemistry in neuroendocrine tumors correlated with in vivo data, based on the evidence that only membrane (rather that cytoplasmic) staining should be considered for a reliable, standardized and clinically relevant report.
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Somatostatin Receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with Somatostatin Receptor scintigraphy.
Modern pathology : an official journal of the United States and Canadian Academy of Pathology Inc, 2007Co-Authors: Marco Volante, Maria Pia Brizzi, Antongiulio Faggiano, Stefano La Rosa, Ida Rapa, Anna Maria Ferrero, Gelsomina Mansueto, Luisella Righi, Silvana Garancini, Carlo CapellaAbstract:Typing Somatostatin Receptor expression in neuroendocrine tumors is of relevance to target Somatostatin analogue-based diagnostic approach and treatment. The expanding use of immunohistochemistry to detect Somatostatin Receptors is to date not paralleled by an accurate methodological setting and standardized interpretation of the results. A multicentric study was designed to compare Somatostatin Receptor immunohistochemical expression with in vivo scintigraphic data and verify its usefulness in the clinical management of neuroendocrine tumors. After methodological setting by testing different Somatostatin Receptor antibodies, 107 cases of neuroendocrine tumors with available Somatostatin Receptor scintigraphy data and pathological material were retrospectively analyzed for Somatostatin Receptor types 2A, 3 and 5 immunohistochemical expression, and compared with scintigraphic images and, whenever available, with the clinical response to Somatostatin analogue treatment. Restricting 'positive cases' to the presence of a membrane pattern of staining, an overall Somatostatin Receptor type 2A immunohistochemistry/Somatostatin Receptor scintigraphy agreement of 77% (chi2 test P