1.Somatostatin Receptor.
Eunhee KIM ; Sookjin SOHN ; Mina LEE ; Heesoon PARK ; Jeechang JUNG ; Seungjoon PARK
Journal of Korean Society of Endocrinology 2003;18(4):342-355
No abstract available.
Receptors, Somatostatin*
;
Somatostatin*
2.Lu-177-Based Peptide Receptor Radionuclide Therapy for Advanced Neuroendocrine Tumors
Keunyoung KIM ; Seong Jang KIM
Nuclear Medicine and Molecular Imaging 2018;52(3):208-215
Peptide receptor radionuclide therapy (PRRT) is a systemic cytotoxic radiation therapy using a compound of β-emitting radionuclide chelated to a peptide for the treatment of tumor with overexpressed specific cell receptor such as somatostatin receptor subtype 2 (SSTR2) of neuroendocrine tumor (NET). Surgical resection should be performed for the curative treatment for NETs when it is feasible; however, a multi-disciplinary approach is needed when locally advanced or metastasized disease. PRRT with lutetium-177 (Lu-177)-labeled somatostatin analogues, as a new treatment modality targeting metastatic or inoperable NETs expressing the SSTR2, have been developed and successfully used for the past two decades. As Lu-177 emits both β- and γ-radiation, it has the ability as a theragnostic agent for NETs compared with only β-emitting yttrium-90 labeled PRRT. Several recent studies reported that Lu-177 gave an overall positive response and improved the patients' quality of life. To fully exploit its potential, large comparative studies are needed for the assessment of distinct efficacies of Lu-177 labeled PRRT. Additionally, for extending the indications and developing new regimens of Lu-177-based PRRT, more dedicated clinical research is required.
Neuroendocrine Tumors
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Quality of Life
;
Receptors, Peptide
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Receptors, Somatostatin
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Somatostatin
3.A Case of Zollinger-Ellison Syndrome with Gastrinoma Localized by 111In-Pentetreotide Scan.
Hyeon Jo JEONG ; Jin Sook RYU ; Jae Seung KIM ; Dae Hyuk MOON ; Hwoon Yong JUNG ; Hyun Kwon HA ; Hee Kyung LEE
Korean Journal of Nuclear Medicine 1999;33(6):537-542
In patient with Zollinger-Ellison syndrome, it is difficult to localize gastrinoma because the tumor is frequently small and multiple. However, accurate localization of the tumor is important for the treatment. Among various imaging modalities, somatostatin receptor scintigraphy (SRS) has been recognized to be the most sensitive tool for the detection of neuroendocrine tumors such as gastrinomas based on the presence of high-affinity binding sites for somatostatin. Recently, we experienced a case of Zollinger-Ellison syndrome caused by gastrinomas which was localized by SRS. This is the first case report of gastrinoma detected by SRS in Korea. SRS can facilitate tumor detection in patient with Zollinger-Ellison syndrome and should be considered as the first-line diagnostic method in the early course of the disease.
Binding Sites
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Gastrinoma*
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Humans
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Korea
;
Neuroendocrine Tumors
;
Radionuclide Imaging
;
Receptors, Somatostatin
;
Somatostatin
;
Zollinger-Ellison Syndrome*
4.Review of Radionuclide Treatment for Neuroendocrine Tumors.
Nuclear Medicine and Molecular Imaging 2006;40(2):90-95
Neuroendocrine tumors (NETs) consist of a heterogeneous group of tumors that are able to uptake neuroamine and/or specific receptors, such as somatostatin receptors, which can play important roles of the localization and treatment of these tumors. When considering therapy with radionuclides, the best radioligand should be carefully investigated. 131I-MIBG and beta-particle emitter labeled somatostatin analogs are well established radionuclide therapy modalities for NETs. 111In, 90Y and 177Lu radiolabeled somatostatin analogues have been used for treatment of NETs. Further, radionuclide therapy modalities, for example, radioimmunotherapy, radiolabeled peptides such as minigastrin are currently under development and in different phases of clinical investigation. For all radionuclides used for therapy, long-term and survival statistics are not yet available and only partial tumour responses have been obtained using 131I-MIBG and 111In-octreotide. Experimental results using 90Y-DOTA-lanreotide as well as 90Y-DOTA-D-Phe1-Tyr3-octreotide and/or 177Lu-DOTA-Tyr3-octreotate have indicated the possible clinical potential of radionuclides receptor-targeted radiotherapy. It may be hoped that the efficacy of radionuclide therapy will be improved by co-administration of chemotherapeutic drugs whose antitumoral properties may be synergistic with that of irradiation.
3-Iodobenzylguanidine
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Hope
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Neuroendocrine Tumors*
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Peptides
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Radioimmunotherapy
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Radioisotopes
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Radiotherapy
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Receptors, Somatostatin
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Somatostatin
5.Clinical Significance of Protein Expression of Cyclooxygenase-2 and Somatostatin Receptors in Gastroenteropancreatic Neuroendocrine Tumors.
Hee Sung KIM ; Hye Seung LEE ; Woo Ho KIM
Cancer Research and Treatment 2011;43(3):181-188
PURPOSE: This study was undertaken to evaluate the significance of cyclooxygenase-2 (COX2) overexpression and the expression of somatostatin receptor (SSTR) subtypes in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS: Two hundred and forty-seven cases of GEP-NET, comprising 86 foregut and 156 hindgut primary NETs, and 5 metastatic NETs in the liver, were studied retrospectively with immunohistochemistry for COX2, chromogranin A, Ki-67, SSTR1, SSTR2, and SSTR5. RESULTS: COX2 overexpression was observed in 54%(126 of 234), and SSTR1, SSTR2, and SSTR5 positivity in 84%(196 of 233), 72%(168 of 233), and 55%(128 of 232), respectively. COX2 overexpression was found to be positively correlated with Ki-67 labeling index and inversely correlated with the expression of SSTR subtypes. In addition, the expression of SSTR subtypes was tightly correlated in any comparative pairs. A significant inverse correlation was found between COX2 and SSTR2 expression in the foregut, but not hindgut NETs. Kaplan-Meier analyses showed that COX2 overexpression (p=0.003) and high Ki-67 labeling index (p<0.001) were associated with poor overall survival (OS), whereas expression of SSTR2 (p<0.001) was associated with better OS of GEP-NET patients. Multivariate analysis revealed negative SSTR2 expression as an independent prognostic marker in GEP-NET patients (p<0.001). CONCLUSION: Our results suggest that expression of SSTR subtypes is associated with favorable prognosis, whereas COX2 overexpression is associated with poor prognosis in GEP-NETs. Taken together, COX2 could be a possible therapeutic target in some subsets of GEP-NETs.
Chromogranin A
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Cyclooxygenase 2
;
Humans
;
Immunohistochemistry
;
Liver
;
Multivariate Analysis
;
Neuroendocrine Tumors
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Prognosis
;
Receptors, Somatostatin
;
Retrospective Studies
;
Somatostatin
6.Clinical Significance of Protein Expression of Cyclooxygenase-2 and Somatostatin Receptors in Gastroenteropancreatic Neuroendocrine Tumors.
Hee Sung KIM ; Hye Seung LEE ; Woo Ho KIM
Cancer Research and Treatment 2011;43(3):181-188
PURPOSE: This study was undertaken to evaluate the significance of cyclooxygenase-2 (COX2) overexpression and the expression of somatostatin receptor (SSTR) subtypes in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS: Two hundred and forty-seven cases of GEP-NET, comprising 86 foregut and 156 hindgut primary NETs, and 5 metastatic NETs in the liver, were studied retrospectively with immunohistochemistry for COX2, chromogranin A, Ki-67, SSTR1, SSTR2, and SSTR5. RESULTS: COX2 overexpression was observed in 54%(126 of 234), and SSTR1, SSTR2, and SSTR5 positivity in 84%(196 of 233), 72%(168 of 233), and 55%(128 of 232), respectively. COX2 overexpression was found to be positively correlated with Ki-67 labeling index and inversely correlated with the expression of SSTR subtypes. In addition, the expression of SSTR subtypes was tightly correlated in any comparative pairs. A significant inverse correlation was found between COX2 and SSTR2 expression in the foregut, but not hindgut NETs. Kaplan-Meier analyses showed that COX2 overexpression (p=0.003) and high Ki-67 labeling index (p<0.001) were associated with poor overall survival (OS), whereas expression of SSTR2 (p<0.001) was associated with better OS of GEP-NET patients. Multivariate analysis revealed negative SSTR2 expression as an independent prognostic marker in GEP-NET patients (p<0.001). CONCLUSION: Our results suggest that expression of SSTR subtypes is associated with favorable prognosis, whereas COX2 overexpression is associated with poor prognosis in GEP-NETs. Taken together, COX2 could be a possible therapeutic target in some subsets of GEP-NETs.
Chromogranin A
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Cyclooxygenase 2
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Humans
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Immunohistochemistry
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Liver
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Multivariate Analysis
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Neuroendocrine Tumors
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Prognosis
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Receptors, Somatostatin
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Retrospective Studies
;
Somatostatin
7.Somatostatin Receptor Scintigraphy.
Korean Journal of Nuclear Medicine 1999;33(1):11-27
Peptide imaging is a new diagnostic modality in nuclear medicine. 111In-pentetreotide (OctreoscanR) is the first commercially available peptide radiopharmaceutical. This review article presents the RESULTS of previous studies using 111In-pentetreotide for several disease states, including neuroendocrine tumors, breast cancer and malignant lymphoma. The use of hand-held probe during surgery and the preliminary RESULTS of radiotherapy using radiolabeled somatostatin analogues are also reviewed. It can be concluded that somatostatin receptor scintigraphy is a promising diagnostic tool for localizing primary tumors that express receptors for somatostatin, staging secondary spread of tumor tissue, following up after therapy and identifying patients who may benefit from therapy with unlabelled or rediolabeled octreotide. The somatostatin receptor imaging will stimulate the development of new radiopharmaceuticals for other receptors and enhance the therapeutic use of radiolabeled peptides.
Breast Neoplasms
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Humans
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Lymphoma
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Neuroendocrine Tumors
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Nuclear Medicine
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Octreotide
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Peptides
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Radionuclide Imaging*
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Radiopharmaceuticals
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Radiotherapy
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Receptors, Somatostatin*
;
Somatostatin*
8.Changes of somatostatin and expression of somatostatin receptor in small intestine and liver tissues during macaque development.
Mei-Mei GUO ; Qing-Hua TAN ; Hua FAN ; Ming-Hui HUANG ; Chun-Hui WANG ; Xiao-Qing QIU ; Cheng-Wei TANG
Acta Physiologica Sinica 2005;57(6):719-724
Intestinal tract, which produces more than fifty kinds of gut peptides, is regarded as the largest endocrine organ. With regard to the gut peptides, a number of studies were focused on their structure, function and the roles in some diseases. The changes in output or distribution of gut peptides in the intestinal tract during development have been largely unknown. This study was aimed to investigate the changes of somatostatin (SST) and somatostatin receptor 2 (SSTR2) in small intestinal and hepatic tissues during the development of macaque. The tissue samples of small intestine, liver or blood samples from peripheral and portal vein of 4 macaques in 6-month fetus, 2-day neonate, 45-day neonate and adult were obtained after anesthetization. The concentrations of SST in blood or tissues of macaques were measured by radioimmunoassay. The distributions of SST in small intestinal or hepatic tissues were visualized by immunohistochemical staining. The expression of SSTR2 was detected by in situ hybridization. SST concentration of intestinal tissue in 6-month-old macaque was (27.3+/-16.6) ng /mg protein and light positive staining of SST was localized in mucosal crypts but negative in muscle layer. The intestinal concentration of SST increased gradually with macaque development and reached to the peak [(120.1+/-35.3) ng /mg protein] in adult. It was significantly higher than that in fetus (P<0.01). Strong positive staining of SST was found in both mucosal crypts and myenteric nerve plexus of adult animal. SSTR2 was obviously expressed in intestinal epithelium of fetus but its expression was greatly reduced in epithelium and was shifted to mucosal crypts when grown to adult. Negative staining of SSTR2 in muscle layer of fetal or neonatal macaque turned to be positive in myenteric nerve plexus of adult. The levels of SST or SSTR2 in liver decreased gradually during development. SST concentrations of small intestinal tissue kept significantly higher than those of hepatic tissues in the macaque developing stages. SST levels of portal vein were also maintained significantly higher than those of peripheral blood in the macaque developing stages. In conclusion, the level of SST and expression of SSTR2 in mucosal crypt increased gradually with macaque development. SST from intestinal tract was quickly degraded in portal vein before entering into liver. SST positive myenteric nerve plexus was visualized only in mature macaque.
Animals
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Animals, Newborn
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Fetus
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Intestine, Small
;
metabolism
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Liver
;
metabolism
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Macaca mulatta
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growth & development
;
metabolism
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Male
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Receptors, Somatostatin
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metabolism
;
Somatostatin
;
metabolism
9.Inhibitory effect of octreotide on the cross excitation of adjacent segment of spinal nerve in rat.
Jun WANG ; ; Dong-Yuan CAO ; Yuan GUO ; Shao-Jie MA ; Yan ZHAO
Acta Physiologica Sinica 2013;65(6):593-599
This study was to observe the effect and possible mechanism of somatostatin analogue octreotide (OCT) on cross excitation of adjacent segment of spinal nerve in rat. Cutaneous branches of T9-T13 spinal dorsal rami were chosen and dissected free for the following recording and stimulation. Only single unit fiber was used for recording, and the adjacent segment of nerve stem was used for antidromic electrical stimulation. To investigate the change of discharge rate and mechanical threshold, OCT and (or) somatostatin receptor antagonist cyclo-somatostatin (c-SOM) were applied to the receptive field following the antidromic electrical stimulation. The result showed that injection of OCT inhibited the increase of discharge rate and the decrease of mechanical threshold induced by the electrical stimulation (cross excitation); c-SOM reversed the effects of OCT. Application of c-SOM alone enhanced the cross excitation effects. The results suggest local application of somatostatin analogue OCT can inhibit the cross excitation between the two segments of spinal nerve by somatostatin receptor.
Animals
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Electric Stimulation
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Octreotide
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pharmacology
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Peptides, Cyclic
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pharmacology
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Rats
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Receptors, Somatostatin
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physiology
;
Somatostatin
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analogs & derivatives
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Spinal Nerves
;
drug effects
10.SSTR2A Protein Expression in Neuroendocrine Neoplasms of the Colorectum.
Young Eun KIM ; Jeeyun LEE ; Young Suk PARK ; Kyoung Mee KIM
Korean Journal of Pathology 2011;45(3):276-280
BACKGROUND: Expression studies of somatostatin receptor type 2A (SSTR2A) in neuroendocrine neoplasms (NENs) led to the development of clinically relevant diagnostic and therapeutic strategies. However, most of these strategies used in-house-developed antibodies and were focused on lung tumors. We evaluated commercially available SSTR2A antibodies in NENs of the colorectum to observe their subcellular localization and distribution within the resected tumor. METHODS: The immunohistochemistry of 77 NENs located in the colorectum were studied using a commercially available antibody against SSTR2A. RESULTS: Most neuroendocrine tumors (NET) grade (G)1 and G2 expressed the SSTR2A in the cytoplasm with apical or luminal localization. However, all neuroendocrine carcinomas (NEC) G3 were negative for SSTR2A. CONCLUSIONS: Our data indicate that SSTR2A immunohistochemistry shows cytoplasmic staining with distinct subcellular localization in most NET G1 in the colorectum using a commercially available antibody. Low or no expression of SSTR2A in NET G2 and NEC G3 raises the possibility that SSTR2A may correlate with histologic differentiation and proliferative activity. Further validation studies in large case series are needed.
Antibodies
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Carcinoma, Neuroendocrine
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Cytoplasm
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Immunohistochemistry
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Lung
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Neuroendocrine Tumors
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Phenobarbital
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Receptors, Somatostatin